Gilenya
An MS Drug Takes a Feisty Approach Aimed at Younger Patients (04/04/13)
The Swiss drug maker Novartis is taking a sassy new tack to win converts to its oral multiple sclerosis treatment, Gilenya. Its “Hey MS, Take This!” campaign shows patients sticking out their tongues with Gilenya capsules on them to show their willingness to fight back against the neurological condition.
The campaign, which begins this week, is aimed at younger people with multiple sclerosis, a chronic autoimmune disease with symptoms like fatigue, difficulty in walking and blurred or double vision. The campaign will be in national print outlets, including a half-dozen national magazines like People, Shape and Self, and on the Web sites of women’s magazine. A television-style online video will also be available on social media outlets.
“MS strikes in the prime of life, and many patients use the Web and social media to connect,” said Dagmar Rosa-Bjorkeson, head of Novartis’s multiple sclerosis unit. “Many are now being diagnosed in their 20s and 30s, and early treatment makes the most impact, so we are trying to target those people who are active and digitally savvy.”
The campaign’s upbeat tone comes, Ms. Rosa-Bjorkeson said, from sentiments patients expressed on blogs and other forms of social media where “people were saying that ‘this disease is not going to stop me.’ ”
“Those were spirited words, with an edginess and power to them that wound up giving the campaign a bolder tone,” she said.
Novartis is trying to set the Gilenya campaign apart from other pharmaceutical advertising.
All such ads must conform to federal regulatory strictures that consumers receive balanced information that not only includes the drug’s effectiveness but also enumerates its risks in consumer-friendly language.
“Since it was approved in 1997, direct contact advertising with consumers has led to a fairly conservative pharma culture,” said Bill Daddi, president of Daddi Brand Communications. “It sometimes leads to people looking at the ads to ask, ‘What’s worse, the symptoms or the cure?’ ”
“But it also encourages people to speak up about their symptoms, which they didn’t always do before,” he said.
Gilenya is in an increasingly crowded treatment market. It is one of three oral therapies that have been approved recently to treat multiple sclerosis, a condition thought to occur when the body’s immune system attacks its nerve fiber insulation.
The Novartis drug is aimed at the most prevalent form of multiple sclerosis, called relapsing, in which the condition can flare up and intensify impairment of neurological function. Novartis says one daily dose of Gilenya helps slow the advance of physical problems that can be brought on by the disease, including shrinkage of the brain.
The new oral pharmaceuticals and other drugs approved in recent years are transforming the treatment of multiple sclerosis, which affects an estimated 400,000 people in the United States and more than two million people worldwide, according to the National Multiple Sclerosis Society. It is commonly treated with drug injections or infusions.
Since its approval by the Food and Drug Administration in September 2010, Gilenya has been used by 28,000 multiple sclerosis patients in the United States. Last year its sales reached $1.2 billion. It competes with products from Bayer, Biogen Idec and Teva in the nearly $9 billion annual market in the United States.
Novartis did not disclose its spending on the Gilenya campaign. But last year, its pharmaceutical ad spending was $95.3 million, according to figures from Kantar Media, a unit of WPP, down from $116.6 million in 2011.
Two-thirds of those with multiple sclerosis are women, and many receive the diagnosis between ages 25 and 44, according to Ms. Rosa-Bjorkeson. A majority of patients use blogs, Facebook, Twitter and YouTube to find information and to connect with fellow sufferers, she said.
The company is using some real patient stories, gleaned from about a dozen patients, on its Web site, gilenya.com, and in brochures and other marketing materials, she said. It plans to add to this as the campaign reaches more people with multiple sclerosis, she said.
“It’s all about attitude,” explained Mike Devlin, creative director of the campaign’s ad agency, Draftfcb, part of the Interpublic Group, which interviewed the multiple sclerosis patients. “There were a lot of nuggets that reflected their voice and attitude, and an outpouring about the impact Gilenya had on their lives.” A 60-second commercial and print ads, he said, “are designed to get people thinking about their treatment choices.”
Featuring real patients “is a contemporary way to get patients to recognize their symptoms and to be more in control,” said Jeff Rothstein, a partner at Cult Health, a Cult360 ad agency. “But pharma ads have to tread a fine line so they are not seen as promoting the idea that patients should just ask the doctor to write a prescription for the drug.”
This is the first broad marketing campaign for Gilenya, which Novartis licensed in 1997 from Mitsubishi Tanabe Pharma and tested in clinical trials. The company says trials have shown the drug to be more effective than interferon treatments, but serious side effects include elevated liver enzymes, headaches, diarrhea and back pain.
Shortly after Gilenya entered the market, Novartis conducted a smaller marketing effort, with ads in magazines aimed at those with multiple sclerosis as well as a limited placement in national magazines.
Its new campaign emphasizes empowered young patients, who use phrases like “No needles for me” and “Take this, you bully” to show their defiant attitude as they cope with the disease.
Source: The New York Times © 2013 The New York Times Company (04/04/13)
Gilenya® Demonstrates Consistent Benefits In Reduction Of Relapses And Brain Volume Loss In Relapsing-Remitting MS(26/03/13)
Data presented at the 65th annual meeting of the American Academy of Neurology (AAN) show Gilenya® (fingolimod), the first and only once-daily oral therapy reimbursed to treat highly active relapsing-remitting multiple sclerosis (RRMS), significantly and consistently reduced the rate of brain volume loss and reduced relapse rates compared to interferon beta-1a IM or placebo.(1,2,4) The new data add to the growing body of evidence for fingolimod regarding its early efficacy benefits and long-term safety profile.
Consistent efficacy: reduction in rate of brain volume loss
Fingolimod continues to show a significant reduction in the rate of brain volume loss by nearly a third and within the first six months of treatment when compared to placebo or interferon beta-1a IM, a commonly prescribed injectable treatment.1 The new analysis of over 3,600 patients from three large Phase III studies (TRANSFORMS, FREEDOMS, and FREEDOMS II) was consistent with previously reported results.(1,5)
Loss of brain volume (also known as brain atrophy) has been observed to occur at higher rates in patients with MS than in the general population. The average rate of brain volume loss in a person without MS over one year is 0.1% to 0.3%.(6)
In the TRANSFORMS study over one year, fingolimod reduced the rate of brain volume loss by 31% compared to interferon beta-1a IM (mean percent brain volume change of -0.31 for fingolimod vs. -0.45 for interferon beta-1a IM; p<0.001). Over two years, fingolimod reduced the rate of brain volume loss compared to placebo by 36% (mean percent brain volume change of -0.84% for fingolimod vs. -1.31% for placebo; p<0.001) in the FREEDOMS study, and by 33% (mean percent brain volume change of -0.86% for fingolimod vs. -1.28% for placebo; p<0.001) in the FREEDOMS II study, respectively.(1)
Consistent efficacy: reduction in relapse rates
Throughout the extensive Phase III programme, fingolimod has consistently shown significant reductions in relapse rates. The most recent addition to this growing body of evidence is new data from the one-year TRANSFORMS extension study (n=341). The study, which included a predictive model to estimate the relapse rate had patients remained on interferon beta-1a IM, showed that patients who were treated with fingolimod experienced a two fold increase in the time-to-first relapse compared with interferon beta-1a IM.(4)
In addition, a subgroup analysis of FREEDOMS II showed fingolimod consistently reduced annualised relapse rates (ARR) compared to placebo in patients with RRMS, across gender, age, prior treatment, and baseline disease activity.(2)
Consistent safety profile: no unexpected safety concerns from new analysis New extension data from FREEDOMS II (n=632) reinforce the known safety profile of fingolimod in patients treated up to four years.7 More than eight out of ten patients (83%) completed the extension study, which identified no unexpected safety concerns.7 With up to seven years of clinical trial experience (Phase II and III) and over two years of real-world use, this adds to the increasing experience of the long-term effectiveness and safety profile of fingolimod in more than 56,000 patients worldwide.(3)
Novartis MS pipeline
The data presented at AAN underscore the depth and breadth of the Novartis MS portfolio and ongoing commitment to addressing unmet patient needs in MS. Alongside the data reinforcing the efficacy and safety profile of once-daily oral fingolimod in RRMS, new data was presented on its potential use in primary-progressive MS (PPMS). New efficacy and safety data were presented on investigational compound BAF312 (siponimod) from the Phase II extension BOLD study in RRMS.(8.9)
It is important to note that the news release contains data that is both within and outside of the UK marketing authorisation for fingolimod.
Additional information on fingolimod
Fingolimod is an effective once-daily oral MS treatment without market authorisation restrictions specific to treatment duration, making it a valuable option for appropriate people with highly active RRMS and the neurologists who treat them10,11
Fingolimod addresses an unmet clinical need and a significant gap in funded treatment options for patients with highly active RRMS who continue to relapse despite treatment with an interferon therapy12
There is increasing experience of fingolimod's long-term effectiveness and safety profile, and approximately 56,000 patients have received the drug worldwide to date3
Fingolimod has been approved in more than 70 countries. In the EU, fingolimod has been launched and reimbursed in a number of markets, including Germany, France, Denmark, Sweden, Norway, Austria, Greece, Italy, Spain, Belgium, Portugal and the Netherlands. Fingolimod also has been launched and reimbursed in other key markets including the United States, Canada, Australia and Switzerland.(13)
Licenced indication for fingolimod(14)
Fingolimod has been licenced for use as a single therapy in the treatment of highly active RRMS in the following adult groups since March 2011:
Patients with high disease activity despite treatment with a beta-interferon. These patients may be defined as those who have failed to respond to a full and adequate course (normally at least one year of treatment) of beta-interferon. Patients should have had at least one relapse in the previous year while on therapy, and have at least nine T2-hyperintense lesions in cranial MRI or at least one Gadolinium-enhancing lesion. A "non-responder" could also be defined as a patient with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year.
Or
Patients with rapidly evolving severe RRMS defined by two or more disabling relapses in one year, and with one or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.
Efficacy of fingolimod(10,11,15,16) The authorisation of fingolimod was based on the submission of data from a large clinical trial programme, which included the TRANSFORMS and FREEDOMS studies
TRANSFORMS showed that fingolimod 0.5 mg reduced the annualised relapse rate by 52% compared to interferon β-1a IM at one year
- this equates to a reduction in annualised relapse rates from 0.33 for interferon β-1a IM to 0.16 with fingolimod 0.5 mg (p<0.001)
FREEDOMS showed that fingolimod 0.5 mg reduced the annualised relapse rate by 54% versus placebo at two years
- this equates to a reduction in annualised relapse rates from 0.40 for placebo to 0.18 with fingolimod 0.5 mg (p<0.001).
Consistent treatment effects were observed in the highly active subgroup for which fingolimod is licenced:
TRANSFORMS showed that fingolimod 0.5 mg reduced the annualised relapse rate by 61% compared to interferon β-1a IM
- this equates to a reduction in the annualised relapse rate from 0.51 for placebo to 0.20 with fingolimod 0.5 mg (p<0.001)
FREEDOMS showed that fingolimod 0.5 mg dose reduced the annualised relapse rate by 71% versus placebo
- this equates to a reduction in the annualised relapse rate from 0.66 for placebo to 0.19 with fingolimod 0.5 mg (p<0.0001).
The clinical trial programme also demonstrated that fingolimod is generally well tolerated with a manageable safety profile when used in accordance with its approved marketing authorisation.10,11 Its benefit/risk profile has been studied in more than 4,000 clinical trial patients, some of whom are in their seventh year of treatment.(17,18)
Safety of fingolimod(10,11,14)
In clinical trials, the most common side effects were headache, liver enzyme elevations, influenza, diarrhoea, back pain, and cough.
Safety considerations in relation to fingolimod treatment:
Liver transaminases: in clinical trials, treatment with fingolimod was associated with asymptomatic liver transaminase elevations
- Recent (i.e. within last 6 months) transaminase and bilirubin levels should be available before initiation of treatment with fingolimod
- In the absence of clinical symptoms, liver transaminases should be monitored at Months 1, 3, 6, 9 and 12 on therapy and periodically thereafter
Macular oedema: in clinical trials, 0.4% of patients treated with fingolimod developed macular oedema, predominantly in the first 3-4 months
- An ophthalmological evaluation is recommended at 3-4 months after treatment initiation
Bradyarrhythmia: initiation of fingolimod treatment results in a transient decrease in heart rate and may also be associated with atrioventricular conduction delays, including the occurrence of isolated reports of transient, spontaneously resolving complete atrioventricular block
- Fingolimod is not recommended in patients concomitantly taking Class Ia or Class III antiarrhythmic medicines
- All patients should have an ECG and blood pressure measurement performed prior to and 6 hours after the first dose of fingolimod
- All patients should be monitored for a period of 6 hours for signs and symptoms of bradycardia with hourly heart rate and blood pressure measurement
- Continuous (real time) ECG monitoring during this 6 hour period is recommended
Infections: fingolimod may increase the risk of infections - Before initiating fingolimod, a recent (within 6 months) complete blood cell count should be available to check peripheral lymphocyte count
- Before initiating fingolimod, patients without a history of chickenpox or without vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV
- Effective diagnostic and therapeutic strategies should be employed in patients with symptoms of infection while on therapy
- Suspension of fingolimod treatment should be considered if a patient develops a serious infection
Blood pressure: in clinical trials, fingolimod was associated with an increase in blood pressure after approximately one month of treatment
- Blood pressure should be regularly monitored during treatment with fingolimod
Pregnancy/breastfeeding: fingolimod may cause harm to an unborn child and women receiving fingolimod should not breastfeed
- Women of childbearing potential should be counselled regarding the potential for serious risk to a foetus and the need for effective contraception during treatment with fingolimod
- A negative pregnancy test is required before initiation of fingolimod treatment
Source: Medical News Today © 2004-2013 MediLexicon International Ltd (26/03/13)
Oral MS drug, Gilenya, Slowed Brain Loss in Study (21/03/13)
Novartis AG said its Gilenya drug to treat multiple sclerosis helped slow brain loss, a measure linked to the severity of the disease.
Patients taking Gilenya in three large Novartis-led studies lost a third less brain volume than patients taking either a placebo or Biogen Idec Inc. Avonex, Novartis said in an e- mailed statement today.
Gilenya was approved in the U.S. in 2010 as the first oral treatment for multiple sclerosis, and cleared for sale in Europe in March 2011. The data may help it beat competition from Sanofi’s oral drug Aubagio, which was brought to market last November, Gordon Francis, who heads Novartis’ clinical science unit for inflammation, said in an interview.
“If I asked you if you’d rather have more brain or less brain, you’d probably say more”, Francis said.
Loss of brain volume is correlated with both the activity and severity of the disease, Francis said.
The results relied on an analysis of data gathered from 3,600 patients with the relapsing form of the disease, and were presented at the annual meeting of the American Academy of Neurology in San Diego.
Source: Bloomberg Business Week ©2013 BLOOMBERG L.P (21/03/13)
Novartis To Present New Data On Multiple Sclerosis Treatment At AAN(13/03/13)
Novartis AG said it will present new data on Multiple Sclerosis or MS treatment at the 65th annual meeting of the American Academy of Neurology or AAN.
It will highlight growing clinical trial and real-world experience with Gilenya (fingolimod), the first once-daily oral therapy approved to treat people with relapsing MS or RMS. Updates on studies of Gilenya in people with primary-progressive MS or PPMS and the investigational agent BAF312 (siponimod) in people with secondary-progressive MS or SPMS will also be communicated, the company said.
"These results, as well as updates on our investigational MS compound BAF312 (siponimod) show that we are making real progress in our commitment to address unmet medical need in MS and to provide a treatment at every stage of the disease," said Timothy Wright, Global Head Development, Novartis Pharmaceuticals AG.
The company sated that data from three large Phase III studies will highlight the efficacy of Gilenya in reducing the rate of brain volume loss, the best characterized magnetic resonance imaging (MRI) predictor of long-term disability. There will also be a presentation on the INFORMS study, which is evaluating Gilenya in patients with PPMS]. This form of MS affects about 10% of people with MS and follows a steady course of worsening neurologic function for which there are no approved disease modifying treatments.
The company stated that additional data will showcase Gilenya's high efficacy and well characterized and manageable safety profile. Latest information shows that the growing real-world and clinical trial experience base for Gilenya now encompasses more than 50,000 patients and 60,000 patient years of exposure worldwide.
New details will be provided on the design of a Phase III study evaluating the efficacy, safety and tolerability of BAF312 (siponimod) in patients with SPMS, which is a sub-type of MS where there are limited treatment options. The vast majority (85%) of people with relapsing-remitting MS will transition to SPMS; 50% within 10 years of disease onset and 90% within 25 years, the company said.
Additionally, the Novartis exhibit at the congress will showcase an expanded Gilenya online and social media platform including the new Gilenya Facebook and GilenyaGo Twitter accounts, YouTube channel, and Gilenya.com mobile site.
Source: RTT News Copyright © 2013 RTTNews (13/03/13)
Encouraging data from oral MS drug Gilenya study analysis
Novartis AG has announced new data that reinforce the generally early and sustained efficacy benefit and long-term safety profile for Gilenya, the first once-daily oral therapy approved to treat relapsing forms of multiple sclerosis, or MS.
Analysis shows significant early treatment effect with Gilenya. A new post hoc analysis of two large Phase III studies shows treatment with Gilenya 0.5 mg led to significant benefits on relapse-related outcomes within the first three months and on brain volume loss by six months compared to placebo.
There was a significant (p<0.05) Gilenya treatment effect on time to first confirmed relapse within three months in both the pivotal FREEDOMS study (n=1272), and FREEDOMS II, the second large Phase III placebo-controlled study (n=1083). The differences between Gilenya and placebo became persistently significant by Day 82 in FREEDOMS and Day 64 in FREEDOMS II, respectively.
Furthermore, in the FREEDOMS study, patients-treated with Gilenya 0.5 mg had on average a 35% reduction in brain volume loss compared with placebo at the first MRI evaluation after six months of treatment (mean percent brain volume change of -0.22 for Gilenya vs. -0.34 for placebo; p=0.006). In FREEDOMS II, there was a 39% reduction in brain volume loss (mean percent volume change of - 0.23 for Gilenya vs. - 0.38 for placebo; p=0.012) at six months.
First results from the PANGAEA observational study in Germany indicate that 90% of investigators and 91% of patients rated Gilenya treatment success, defined as efficacy and tolerability, as Good or Very Good. PANGAEA is a German registry study aimed to enroll a total of 4,000 patients with a follow-up of five years designed to investigate the efficacy and safety of Gilenya in everyday clinical practice. As of May 2012, one year after initiation of the registry, more than 1,850 patients were enrolled in 475 participating centers. These results also showed an overall safety profile in line with previously reported data.
In addition, a separate analysis of time to discontinuation of therapy among MS patients receiving Gilenya and other disease modifying treatments (DMTs) using pharmacy claims in the US (n=1891) show Gilenya-treated patients were significantly less likely to discontinue treatment over the 12 month observation period (Gilenya: 27.8%, other DMT cohorts: 42.7-54.5%; p<0.01) and discontinued later than patients using injectable DMTs.
A new integrated analysis of safety data from Phase II, Phase III and study extensions for fingolimod (all doses, n=3553) show a safety profile generally consistent with previous results. The total fingolimod exposure was 9,070 patient years, with 1,510 patients treated for more than three years and some for more than seven years.
As of August 2012, more than 49,000 patients have been treated with fingolimod in clinical trials and in the post-marketing setting, and there is approximately 52,000 patient years of exposure.
Gilenya, licensed from Mitsubishi Tanabe Pharma Corporation, is the first in a new class of compounds called sphingosine 1-phosphate receptor (S1PR) modulators. It has demonstrated superior efficacy compared to Avonex, a commonly prescribed treatment, showing a 52% relative reduction in annualized relapse rate (primary endpoint) and a 40% relative reduction in the rate of brain atrophy (secondary endpoint) at one year in a pivotal head-to-head trial in patients with relapsing-remitting multiple sclerosis. In a recent post hoc sub-group analysis, Gilenya showed a 61% relative reduction in annualized relapse rate compared to interferon-beta-1a (IM) at one year in subgroups of patients with highly active relapsing-remitting MS not responding to interferon treatment.
"As the first once-daily oral MS therapy, growing real-world experience reinforces Gilenya's high efficacy and long-term safety profile," said David Epstein, head of the pharmaceuticals division of Novartis Pharma AG. "With data showing an early treatment effect on relapses and brain volume loss, Gilenya continues to show positive outcomes for patients and Novartis remains committed to addressing the significant remaining unmet medical need in the MS community."
"Understanding the onset of efficacy is an important consideration in the treatment of MS as early effective treatment may improve patient outcomes," said Professor Ludwig Kappos, chair of neurology, University Hospital, Basel, Switzerland. "The new analysis of Phase III data shows a significant early effect of Gilenya on relapses and MRI measures, and further supports its role as a valuable treatment option for relapsing-remitting MS."
Source: equities.com Copyright © 2012 equities.com (17/10/12)
Gilenya reduces brain loss in Multiple Sclerosis patients
Pooled data from two large Phase III studies have demonstrated a significant early treatment effect of Novartis' multiple sclerosis pill Gilenya on relapses and MRI outcomes, including brain volume loss.
The data, presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress in Lyons, France, shows that treatment with Gilenya (fingolimod) led to significant benefits on relapse-related outcomes within the first three months and on brain volume loss by six months compared to placebo. Specifically, in the FREEDOMS study, treatment with the once-daily pill resulted in, on average, a 35% reduction in brain volume loss compared with placebo after six months of treatment. In FREEDOMS II, there was a 39% reduction.
David Epstein, head of Novartis Pharma, said that "as the first once-daily oral MS therapy, growing real-world experience reinforces Gilenya's high efficacy and long-term safety profile". The company also quoted Ludwig Kappos, chair of neurology at University Hospital, Basel, Switzerland, as saying that "understanding the onset of efficacy is an important consideration in the treatment of MS as early effective treatment may improve patient outcomes".
Other Novartis data presented at ECTRIMS includes first results from 1850 patients enrolled in the PANGAEA observational study in Germany. This shows that 90% of investigators and 91% of patients rated Gilenya treatment success, defined as efficacy and tolerability, as 'good' or 'very good'.
In addition, a separate analysis of time to discontinuation of therapy among MS patients receiving Gilenya and other disease modifying treatments (DMTs) using pharmacy claims in the US (n=1891) show Gilenya-treated patients were significantly less likely to discontinue treatment over the 12 month observation period (Gilenya: 27.8%, other DMT cohorts: 42.7-54.5%) and discontinued later than patients using injectable DMTs.
Source: PharmaTimes Copyright 2012 (15/10/12)
Battle lines drawn in the MS oral drugs market
For years, patients with multiple sclerosis had to endure injection therapies to stave off the horrible disease. Oral medications have finally emerged from development recently, and it turns out the competition is heating up fast: Results arrived on two major clinical trials for Biogen Idec's own oral MS drug, BG-12, and the data looks rock-solid. With the MS market suddenly red-hot, will Biogen's latest success propel the company to higher heights?
Mopping up the competition
Biogen's two phase 3 trials for BG-12 came out in Wednesday's New England Journal of Medicine with promising results. The two trials demonstrated strong efficacy for BG-12, with chronic relapses falling 44% to 51% at the two-year mark. Given that drugs currently used to combat MS relapses typically demonstrate only a 30% improvement, BG-12's success looks sharp.
While the FDA won't rule on BG-12's approval until later in the year, Biogen's drug looks to become just the third oral medication for MS on the market. Sanofi's Aubagio received the green light from the FDA earlier this month, following Novartis's Gilenya, the first oral MS treatment launched in 2010.
Unfortunately for Biogen's two competitors, their drugs come with serious questions over efficacy and side effects. Gilenya has caused numerous headaches for Novartis, with the FDA issuing a restrictive label for the drug after a patient died soon after beginning treatment. While the connections between the death and the drug were unclear, the fact that Gilenya also can slow patient heart rates -- and that patients are recommended to stay in a hospital for six hours after the first dose -- aren't helping Novartis' PR department.
Sanofi might not face the same sort of lethal problems with Aubagio, but regardless of Aubagio's warm reception around projected future sales, early signs show that BG-12 is simply a better product. In one trial, Aubagio failed to beat the Rebif injection treatment offered by Pfizer with Aubagio sporting only a 30% relapse reduction. BG-12 leads with a considerable advantage in a head-to-head matchup of efficacy.
Concerns and answers
Ironically, the hurdles hit by these two drugs -- Gilenya in particular -- could come back to haunt Biogen. With doctors used to effective injection medications for MS, the problems of the past could make individual practitioners hesitant to dole out a third oral treatment. National MS Society Chief Research Officer Timothy Coetzee cautioned BG-12's spread on this very issue, stating, "My guess is that the injectables will remain an important treatment option." He warned that a wide-scale replacement of injection treatments with oral drugs is still up in the air.
Still, BG-12 is a potent drug. The twice-daily treatment in one clinical trial proved to reduce new MS-linked brain lesions by 71%. The drug also lacks the problematic side effects of Gilenya, with the most common problems being digestive issues such as abdominal pain and diarrhea. Such side effects also diminished in number in the clinical trials after the first treatment month.
Additionally, Biogen has plenty of ways to combat MS on the market already. Its MS injection therapy developed jointly with Elan Tysabri, is prescribed for first-line MS treatment in Europe. Tysabri still recorded 69,000 patients as of July and grew year-over-year annual revenue by more than 10% in 2011 for Biogen.
BG-12's U.S. patents won't expire until 2019 at the earliest, so if it's approved, Biogen will have plenty of time to make inroads on a lucrative and growing MS market. Biogen further estimates that BG-12 would hold eight years of data exclusivity and an additional two years of market exclusivity in the European Union, effectively stringing out maximum sales in the Western world's most powerful consumer markets until the next decade.
Biogen's steady stream of optimism
Biogen's still a solid company with a strong financial future on top of all that. It boasts a steady pipeline of 12 drugs and therapies in phase 2 trials or later, including BG-12. The company's best-selling drug, Avonex, took in more than 50% of the company's revenues, and Biogen holds exclusive rights on the drug until 2026.
The strong majority of Biogen's $5 billion in annual revenues stemmed from MS treatments in 2011 -- a market that will reward Biogen and its shareholders even more as it grows from a current $9.6 billion market last year to an estimated $14 billion by 2015, according to JPMorgan Chase projections. If medical professionals sign on to the prescription of oral MS treatments, it's common sense to think that patients would go for the hassle-free therapies over painful injections -- allowing BG-12 and Biogen to further tighten the company's grip on this market.
Don't bet the farm on Biogen before the FDA rules on BG-12's approval, but for right now, everything's looking optimistic for this MS drug. It's up for debate whether BG-12 will hit superstar status, but with Gilenya already selling reasonably well and projections for Aubagio high, BG-12 could take the lead in a promising market. Biogen may be trading at all-time highs, but the coming returns could soundly trump what we've seen so far from this booming biotech stock.
Source: Daily Finance © Copyright 2012 AOL Inc.
Scottish MS patients finally given access to oral MS drug Gilenya®
The Scottish Medicines Consortium (SMC) has today announced that Gilenya® (fingolimod), the world’s first pill for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS), has now been approved for restricted use within NHS Scotland.
Today’s decision means that people with highly active RRMS not responding to treatment with first-line interferon injections now have the option of switching to fingolimod as their next step, bringing Scotland in line with the rest of the UK. Until now, people with MS in Scotland have had to self-inject at least weekly or travel to hospital for infusions to manage their condition.
As part of today’s landmark decision, SMC clinical experts recognised the significant unmet need for an effective oral treatment for those people failing on first-line interferon injections, highlighting the important patient and service benefits an oral treatment would bring.
Having reviewed a wealth of data, including sub-group data, the SMC acknowledged the clinical effectiveness of fingolimod as part of its decision. The SMC recognised that fingolimod significantly reduced relapse rates (by 52%) when compared to a standard injection (interferon ß-1a IM). Furthermore, they noted that fingolimod showed broadly similar efficacy and demonstrated cost-savings when compared to infusion therapy (natalizumab).
Dr Belinda Weller, a consultant neurologist who took part in the clinical trials for fingolimod in Scotland, commented, “Scotland has the highest incidence of MS in the world, so the availability of an effective oral treatment for people whose injections are no longer working is fantastic news. Not only is fingolimod very effective, but also more convenient, which is very important considering the geography of Scotland.”
Until today’s decision, the Scottish were the only people in the UK not to have access to fingolimod on the NHS, despite having the highest incidence of MS in the world with 10,000 people affected. Fingolimod has been approved by the National Institute of Health and Clinical Excellence (NICE) since April 2012 and over 41,000 people have been treated worldwide to date. Importantly, there is no limit on the duration of time for which fingolimod can be taken.
In March 2012, the SMC initially rejected the use of fingolimod on NHS Scotland. Key to the positive decision was the involvement of patient and professional groups, including the MS Society Scotland, MSPs and the MS medical community, who recognised the unmet clinical need for an effective oral treatment for those people failing on injections.
Commenting on the decision, Dr Mark Bechter, Medical Director ad interim at Novartis UK, said: “This is a landmark day for the Scottish MS community and we are delighted that our continued collaboration with the SMC has resulted in a positive decision. We are looking forward to working with the Scottish NHS Boards to ensure appropriate people with MS have access to fingolimod as soon as possible.”
Source: Novartis (10/09/12)
Rethink on MS pill Gilenya gives hope to Scots sufferers
Multiple sclerosis sufferers in Scotland will learn today if the world’s first oral pill to alleviate symptoms of the condition is to be prescribed on the NHS.
The drug, Fingolimod, is already available to MS patients in England and Wales after being approved by the National Institute for Clinical Excellence in March. But the Scottish Medicines Consortium, which evaluates drugs for use in Scotland and ruled earlier this year that it did not provide value for money, has now reconsidered its decision.
The earlier judgment sparked anger among campaigners in Scotland, which is believed to have the highest rate of MS in the world, with approximately 10,500 diagnosed cases.
At present people with MS have to receive a weekly injection of interferon to slow progress of the disease of a monthly infusion of Tysabri.
Those who receive regular injections claim they have a “six day week”, with one day wiped out by the debilitating effects of the treatment.
Patients claim that taking a daily pill would improve their quality of life and avoid unnecessary doctors’ appointments. For those who live in remote island communities, where there are significant numbers of MS sufferers, it would put an end to lengthy journeys to and from mainland hospitals.
MS damages the central nervous system, leading to a range of disabilities including co-ordination difficulties and visual impairment. The reasons for Scotland’s high rates of the condition remain unknown, although it is thought a lack of sunshine and Vitamin D may trigger the illness.
Fingolimod, also know as Gilenya, is said to reduce relapse rates among MS sufferers by around 50%. It has been approved for use in 35 countries including the United States and Germany.
Campaigners says as well as improving quality of life, Fingolimod is also cost effective. The annual bill for treating one patient with the pill is estimated at around £19,665 while the cost for Natalizumab, the drug used in monthly infusions, is around £21,257.
Hospital stays for patients who suffer a relapse cost the NHS more than £30,000 per admission. Only a small number of Scots have been prescribed the drug after their GPs requested funding for consideration on a “case by case” basis from health trusts.
Gillian Rafferty, 48, from Moffat, is one who has been taking part in a trial for Fingolimod after her GP referred her to specialist MS nurses in Carlisle. “I started taking the drug in 2007 and since then I’ve had no relapses or MS symptoms. Before that I had to take steroids to manage the symptoms when I had relapses,” said Rafferty.
“I had one when my daughter Sarah was 11 months and I couldn’t feel anything down my right side. I was terrified of dropping her and couldn’t do up her BabyGro.”
Rafferty added: “It’s not really fair that people are getting Fingolimod in England and Wales. I’d always thought that the attitude here in Scotland was usually more go-ahead in health matters, especially since we’ve got more people with MS in the world as a percentage of the population. I’m hoping that injectables will become a thing of the past.”
Becky Duff, head of policy and communications at MS Society Scotland, which expressed disappointment at the SMC decision in March, said: “We would welcome any decision that would increase the treatment options for people with highly active MS.
“For the past 10 years, people with MS have needed to inject to receive their medicines – a pill represents a significant step forward and will greatly improve quality of life.”
Announcing their decision not to make Fingolimod available in Scotland, the SMC acknowledged there was evidence of a reduction in relapse rates. But they claimed it had not been compared to another drug available in Scotland and that it could be responsible for a short-term decrease in heartbeat, swelling of the retina inside the eye and that about half of the patients monitored went on to develop infections.
A spokesperson for the SMC said: “We were disappointed not to be in a position to accept Fingolimod as a value for money medicine for use within the NHS in Scotland when we assessed the manufacturer’s evidence in March of this year.
“Unfortunately there were weaknesses in the economic case presented by the manufacturer that meant that it was not considered cost-effective. However, we’re pleased that the manufacturer has been quick to come back to us with a revised submission. We will be making a new announcement on Monday.”
Source: Scotsman.com © 2012 Johnston Publishing Ltd (10/09/12)
Oral MS drug piloted in North East is available on the NHS
NHS funding for a groundbreaking drug piloted in the North East for patients with multiple sclerosis is now mandatory.
The National Institute for Clinical Excellence (Nice) has stipulated that adults with relapsing remitting MS not responding to treatment with first-line interferon injections should have access to fingolimod, an oral pill that cuts relapses by more than half compared to a standard injection.
Clinical trials that began in 2004 at the regional centre for the treatment of MS at Newcastle’s Royal Victoria Infirmary (RVI) has meant patients in the North East were among the first worldwide to try fingolimod.
Now all eligible patients should have access to the daily pill, which is proven to be twice as effective as a standard injection. Dr Martin Duddy, consultant neurologist at the RVI said: “A number of patients at our centre have already started treatment with fingolimod and we anticipate these numbers will increase over the coming months.
“Our patients are keen to get started on treatment and we are delighted to be one of the first centres in the UK to have our service up and running.
“It is an important step forward and it gives us another option in the treatment for MS patients.”
Fingolimod, which is also known by the brand name Gilenya, has taken many years to develop and 38,000 patients worldwide are already using the treatment.
In April this year, Nice approved it for use on the NHS, confirming it is a valuable, innovative and cost-effective therapy.
Following publication of final Nice guidance, the NHS is obliged to provide funding and resources for recommended treatments within three months.
Within the last month eight patients at the RVI have been prescribed fingolimod, and it is anticipated that an extra eight to 10 patients a month will be given the medication.
It is hoped that access to the treatment will help reverse the current trend highlighted by a 2010 report from leading expert Prof Mike Richards.
This showed that the UK is ranked 13th out of 14 countries when it comes to access to new treatments for MS.
MS is the most common neurological condition affecting young adults.
It is estimated that more than 100,000 people in the UK have the illness and it can occur at any age but is usually diagnosed between the ages of 20 to 40.
In MS, white blood cells attack the coating of the nerve cells which help messages from the brain travel to the rest of the body.
As these cells are damaged, people experience symptoms such as numbness and tingling, blurred vision, mobility and balance problems, and muscle weakness and tightness.
Fingolimod works by preventing the white blood cells from attacking nerve cells in the brain and spinal cord.
Angela Hamilton has suffered with the condition for 15 years and experiences pain and fatigue.
The 45-year-old, of South Shields, said the development to make NHS funding mandatory for fingolimod offered hope to those living with the debilitating condition.
“It is really brilliant news and it’s an excellent decision by Nice,” explained the policy and information officer.
“It’s helping to take away patient’s anxiety about the condition as you know that there is a treatment option available if you relapse.
“Anything that’s a step forward and a development in the type of medication and treatment offered is welcomed.”
We are delighted to be one of the first centres in the UK to have our service up and running
Source: The Journal © 2012 ncjMedia Limited (26/07/12)
MS drug Gilenya prescriptions slowing due to lack of monitoring facilities
Novartis’ multiple sclerosis (MS) pill Gilenya faces slowing prescriptions in New York because of a lack of facilities to perform first-dose observations, neurologists told Biopharm Insight. However, Novartis has been in contact with a number of clinicians and is working on increasing the number of sites.
A US Food and Drug Administration (FDA) review was initiated after a patient died within 24 hours of taking the first dose of Gilenya. Regulatory authorities also re-evaluated study data regarding the drug’s effect on heart rate and blood pressure.
Gilenya is now contraindicated for use in patients with certain pre-existing or recent heart conditions or stroke, or those taking certain antiarrhythmic drugs, according to FDA. Extended monitoring is recommended in patients with QT prolongation and in patients who are already taking medication that slows heart rate. Observation includes continuous overnight electrocardiography (ECG) monitoring.
A Novartis spokesperson said via email the company is committed to helping healthcare providers implement the updated prescribing information recommendations.
Gilenya sales in 2011 reached USD 494m.
Monitoring requirements and set up
There is no official Novartis-arranged facility in Manhattan to perform first-dose observations at this time, but this is likely to change in the very near term, according to Dr Stephen Krieger, assistant professor of neurology, Corinne Goldsmith Dickinson Center for MS, Mount Sinai Medical Center, New York. Dr David Snyder, director of the Multiple Sclerosis Center at New York Hospital Queens, added there is no facility available in New York City. “There is a facility in Secaucus, New Jersey, where one [of my] patients in New York is going,” he noted.
At his hospital, Snyder noted that he is not in a position to do an ECG. He noted that patients need to be referred to a cardiologist to assess if the patient can take Gilenya. “We don’t repeat the ECGs in our office, but now the new guidelines indicate that you do need to get ECGs before and after dosing. We cannot do that,” Synder explained.
He said the same issue is likely to affect other private practice neurologists. Dr Aaron Miller, professor of neurology at the Mount Sinai School of Medicine, said there are one or more sites in New York that have been identified to conduct monitoring. “We work directly with Novartis to find a site,” he said.
Novartis currently has a system in place with a “nurse navigator” to facilitate arranging monitoring and first dosing, Krieger noted. He said he believed this program is being updated to arrange first-dose centers that meet the new, heightened requirements.
If a neurologist wishes to arrange the first-dose observation themselves, then either hospital admission or contracting with a facility that can perform continuous monitoring can be done, Krieger added.
This would likely be akin to Biogen Idec’s “TOUCH-certified” infusion centers for Tysabri administration in the US, he added. The TOUCH program monitors deaths, and physicians know the risks with Tysabri, stated Dr Karen Blitz-Shabbir, director of the North Shore MS Care Center in East Meadow, New York.
Physicians can stratify risks with Tysabri, while Gilenya is more difficult because we do not know how people are dying, she said. Blitz-Shabbir said two of the 11 deaths associated with Gilenya were from drowning and appear to be cardiac-related. There has been no information given to physicians about the cause of these patients’ deaths, she noted.
Novartis needs to expand its Gilenya Go program to a more comprehensive case-management system for doctors and patients to be able to efficiently use the drug, said Dr Daniel Kantor, president of the Florida Society of Neurology, who was an investigator on Gilenya. Kantor said he is currently trying to figure out what to do for patients who need hospitalization. In the US, Novartis continues to offer pre-tests and first-dose observation capabilities at a network of clinical centers that provide assessments and screenings, but not 23 hour observations, that may be needed by patients taking Gilenya called the Gilenya Assessment Network (GAN), the spokesperson said. It currently comprises close to 250 sites around the country, and sites are accessible within 30 miles of Novartis’ customers and growing rapidly, the spokesperson added.
Gilenya’s efficacy is still great, but it’s really the logistical factors associated with the drug, Kantor noted. The safety data suggests that despite some questions in clinical practice, Gilenya is overall associated with a very low chance of cardiac signs or symptoms, noted Kantor. Because of recent events, Snyder said his prescribing process has slowed down somewhat. If patients are doing well on the current injectables, Snyder said he would not switch to an oral drug just because of patient convenience. In terms of the number of unexplained deaths, one US patient who was on Tysabri and then was switched to Gilenya, developed progressive multifocal leukoencephalopathy (PML) shortly after the change, Snyder said.
Declining use
MS centers are using it less frequently, and it’s mostly used by general neurologists rather than MS specialists, Blitz-Shabbir said.
Gilenya’s efficacy is still great, but it’s really the hassle factor associated with the drug, Kantor noted.
Some of the unexplained deaths were due to inappropriate patient selection by the physicians involved, Snyder stated. “I emphasized that the patients that we select for Gilenya use are young, free of any CV disease, and are not on any medications that would affect the heart.”
As neurologists refine the concept of the “appropriate patient” for Gilenya, with limitations regarding cardiac history and concomitant medicines that can impact heart rhythm, there may be a modest slowing of prescriptions, said Krieger.
The likely approval of Sanofi’s teriflunomide and Biogen’s BG-12 in the coming year may also impact use of Gilenya, as it may cause neurologists to hold off on switching a patient to this oral medication in anticipation of additional options, said Krieger.
Gilenya is a very interesting drug and it affects the S1P receptor, which is on every cell, and every organ in the body, Blitz-Shabbir explained.
A neurologist on background said one concern when Gilenya was approved was the fact that the circulating white cells decrease, so nobody really knows the long-term effects.
The reason why patients are willing to go on Tysabri is because it’s the most efficacious drug on the market, Blitz-Shabbir claimed. She said she was unsure whether Gilenya is the best drug, adding it doesn’t warrant the risk. Dr Samuel Hunter, a neurologist at the Advanced Neurosciences Institute in Tennessee, said Gilenya will be a “huge pain” for the majority of patients. Costs have been increased and inconvenience thousands of people for the benefit of rare individuals who are easily identified as being at risk by history and ECG, he said. Physicians do not want to take the time or trouble to screen these issues, especially unnecessarily, he added.
Source: The Financial Times Copyright The Financial Times Limited 2012 (04/07/12)
Oral MS drug Gilenya slows brain inflammation
The multiple sclerosis medication fingolimod (Gilenya) led to "rapid and sustained" reductions in MRI-documented inflammatory lesion activity, researchers reported.
In a two-year randomized trial, the medication also slowed the rate of brain volume loss compared with placebo, according to Ernst-Wilhelm Radue, MD, of University Hospital Basel in Basel, Switzerland, and colleagues.
Changes in lesion volume over time also favoured the medication rather than placebo, Radue and colleagues reported online in Archives of Neurology.
Combined with previously reported improvements in relapse rates and disability progression, the findings suggest that the drug -- a sphingosine 1–phosphate receptor (S1PR) modulator -- has a "positive impact on long-term disease evolution," the researchers argued.
Fingolimod inhibits migration of T cells out of lymph nodes, preventing them from attacking the protective myelin sheaths surrounding nerve fibers. The drug, in an oral formulation of 0.5 milligrams, was approved in 2010 on the basis of its effects on relapse and disability.
The current study looks at magnetic resonance imaging (MRI) of the 1,272 patients who were part of the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial.
Participants were randomly assigned to get once-daily fingolimod capsules of 0.5 mg or 1.25 mg, or to placebo and had standardized MRI scans at screening and at 6, 12, and 24 months.
The scans were evaluated for the number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions, Radue and colleagues reported, as well as for the percentage of change in brain volume.
They found:
Both fingolimod doses significantly reduced (P<0.001) the number of new or newly enlarged T2 lesions over 24 months compared with placebo.
The reductions reached significance by month 6 and remained significant for the rest of the study.
Fingolimod patients at either dose also had fewer gadolinium-enhancing lesions and lower lesion volumes at 6, 12 and 24 months than patients treated with placebo (P<0.001 for all).
Over the 24 months, 21% of placebo patients were completely free from new or newly enlarged T2 lesions, gadolinium-enhancing lesions, or both, compared with 52% and 50.7% of those treated with the high and low doses of fingolimod, respectively (P<0.001).
Changes in T2 hyperintense and T1 hypointense lesion volume also favored fingolimod over placebo, (P<0.05 for all).
Both doses of the drug slowed the loss of brain volume compared with placebo (P<0.001) over the whole study period. The improvement was significant by month 6 and was sustained, with relative reductions in brain volume loss, compared with placebo, of 23% to 45% at the various intervals.
The findings "confirm that the efficacy of fingolimod therapy is robust across all MRI end points," the authors argued.
The study was supported by Novartis Pharma AG. Radue reported financial links with Bayer Schering, Biogen Idec, Novartis, Merck Serono, Actelion, and Basilea Pharmaceutica.
Primary source: Archives of Neurology
Source reference: Radue E-W, et al "Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis" Arch Neurol 2012; DOI: 10.1001/archneurol.2012.105.
Source: MedPage Today © 2012 Everyday Health, Inc (03/07/12)
Gilenya® shows long-term efficacy and safety in extension of phase III head-to-head study
New long-term data for Gilenya® (fingolimod), the only oral therapy approved to treat people with relapsing forms of multiple sclerosis (MS), show a sustained efficacy benefit and a consistent safety profile with up to 4.5 years of continuous treatment. These results, from an extension of the phase III head-to-head TRANSFORMS study, also showed improved efficacy for patients switched to Gilenya from Avonex® (interferon-beta-1a IM), a commonly prescribed MS treatment.
"These data further reinforce our confidence in Gilenya's long-term effectiveness and safety profile. The TRANSFORMS extension study shows that MS patients treated continuously with Gilenya for up to four and a half years demonstrated sustained low levels of clinical and MRI activity," said Tim Wright, Global Head of Development, Novartis Pharma. "Furthermore, patients who switched to Gilenya from interferon beta-1a IM showed a reduction in relapses and improvements in MRI measures in the extension compared to the core study."
In the core TRANSFORMS study, Gilenya demonstrated superior efficacy to interferon-beta- 1a IM, reducing the annualized relapse rate (ARR) by 52% at one year (Gilenya 0.5 mg, ARR = 0.16; interferon-beta- 1a IM, ARR = 0.33; p<0.001. The extension study showed that this low relapse rate was sustained in patients receiving continuous treatment with Gilenya (n=356) for up to 4.5 years (Gilenya 0.5 mg, ARR core study = 0.16; ARR extension study = 0.16). The data from the extension study also showed that patients treated with Gilenya continuously maintained a low brain atrophy rate throughout the study as measured by assessing brain volume loss, which is valued as a predictor of long-term disability.
For patients who switched to Gilenya for the open-label extension study (n=167), their ARR was 0.33 in the core study when treated with interferon-beta-1a IM and 0.20 in the extension phase when treated with Gilenya (n.s.). Patients in the switch group also displayed a slowing of brain atrophy following the switch to Gilenya.
These extension data from up to 4.5 years also showed long-term treatment with Gilenya was generally well tolerated with a safety profile consistent with pivotal trials. In line with previous studies, including the core TRANSFORMS study, the most common adverse events were nasopharyngitis, headache, and upper respiratory tract infections. Switching therapy from IFN beta-1a to Gilenya did not reveal any new or unexpected safety concerns. On treatment initiation, a low incidence of asymptomatic transient bradycardia was observed in patients who switched from interferon-beta-1a IM to Gilenya (IFN-0.5 mg [0.6%]), which resolved without treatment. Overall cardiac events were similar across all patient groups.
In addition, all patients treated with Gilenya in the extension phase, regardless of original treatment in the core study, showed comparable percentage of patients free from MRI disease activity by the end of the study. (free from gd enhanced t1 lesions:77.4% in switch group vs. 74.7% Gilenya 0.5mg)(free from new/newly enlarged t2 lesions:45.0% in switch group vs. 42.0% Gilenya 0.5mg). The continuous and switch groups did not significantly differ with respect to disability progression at the end of the study.
"This extension study data provide deeper insight into the efficacy and safety profile of fingolimod", said Dr. Xavier Montalban, Director of the Multiple Sclerosis Center of Catalonia and of the Unit of Clinical Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain. "The results, which are consistent with the pivotal phase III studies, confirm that fingolimod is highly effective in treating relapsing forms of MS, and as the first available oral MS treatment, continues to be a valuable treatment option for appropriate patients."
TRANSFORMS was a large phase III double-blind, double-dummy, head-to-head study that involved 1,292 patientswith relapsing-remitting MS that was conducted over one year, comparing the efficacy and safety of Gilenya to interferon-beta-1a IM. At the end of the 12-month core study, eligible patients could enroll in the extension study, which ran for an additional 3.5 years. Patients on once-daily oral Gilenya remained on drug and those who had been treated with interferon-beta-1a (IM) switched to Gilenya for the duration of the extension study.
These data were presented at the 22nd Annual Meeting of the European Neurological Society (ENS), taking place 9-12 June 2012 in Prague, Czech Republic.
As of February 2012, approximately 36,000 patients have been treated with fingolimod in clinical trials and in the post-marketing setting, some up to seven years, and currently there is approximately 34,000 patient years of exposure.
Source: MarketWatch Copyright © 2012 MarketWatch, Inc (11/06/12)
Multiple Sclerosis: the disease of a thousand faces
A new drug for treating multiple sclerosis (MS) has yet to be made available by the state, forcing sufferers to buy at their own expense, according to the Cyprus Multiple Sclerosis Association.
“The approval of the first pill for MS, called Fingolimod (trade name Gilenya), which is a ray of hope for MS sufferers, has taken us one step back, because this medication has still not been incorporated into our national formulary,” said the Association’s head Lenia Takoushi.
She was speaking at a news conference yesterday to mark World MS Day, under the banner: ‘The disease of a thousand faces’.
Fingolimod is a drug approved to reduce the rate of relapses and progression of the disease in cases of relapsing MS.
MS is an autoimmune disease that affects the brain and central nervous system. Symptoms, including loss of balance, muscle spasms and problems walking, vary because the location and severity of each attack can be different. Episodes can last for days, weeks or months and these episodes alternate with periods of reduced or no symptoms.
Takoushi said that in a meeting the Association had with the Health Minister, he promised that over the next few weeks the drug would be added to the list of those available from the state, provided that parliament releases the funds needed.
She said the sooner the funds were released the better, as some sufferers had been paying for the medication themselves.
Takoushi also raised the issue of employment of MS sufferers and disabled people in general. “We congratulate the ministry and government for adopting the law (new legislation allows for 10 per cent of public sector positions to be filled by people with disabilities) but there are weaknesses (in the system) when it comes to MS sufferers, due to the uniqueness of the disease,” she said.
She explained that a sufferer may not fulfil the criteria if they happen to be present before the medical board on one of their ‘good days,’ and may therefore not be hired.
Up till now no MS sufferer has been hired (under the legislation), added Takoushi.
Labour Minister Sotiroulla Charalambous said the ratification of the UN convention on the rights of disabled persons was a milestone for the hiring of disabled persons in the public sector and the reorganisation of vocational training and rehabilitation of people with disabilities.
With a view to making the public more aware of the disease Takoushi said: “As a society we must learn to understand and respect this diversity and this uniqueness of MS…….and we have to admit that in Cyprus we still have a long road ahead of us.”
We’re not talking about feeling sorry (for them) but about equal rights and equal opportunities, she added.
Source: Cyprus Mail 2012 Cyprus mail Ltd (31/05/12)
FDA issues new advice on oral MS drug Gilenya
As their European counterparts did last month, the FDA has recommended continued use of the Gilenya multiple sclerosis pill sold by Novartis, but did say the drug should carry stronger warnings about heart risks and that some patients should undergo increased monitoring. The move was largely expected after the European Medicines Agency issued a similar alert, despite arguments by a non-profit safety watchdog that further restrictions are needed.
Although cardiovascular risks were known at the time of approval two years ago, the regulatory review was undertaken in response to patient deaths, including an unexplained sudden death of one person within 24 hours after taking Gilenya for the first time (back story). The back-to-back regulatory decisions will likely ease investor concerns over the prospects for the pill, which Novartis continues to hope will generate blockbuster sales.
The drugmaker has been counting on Gilenya to help compensate for the loss of patent protection on such big-selling drugs as the Diovan blood pressure pill. Meanwhile, competition in the MS market looms as Biogen Idec plans to seek FDA approval for an oral pill shortly.
Last month, Novartis execs maintained that between just 4 percent and 7 percent of MS patients may be at risk for the sort of cardiovascular issues that prompted the FDA and EMA reviews.
The FDA advised doctors not to prescribe Gilenya to patients with a history of cardiovascular and cerebrovascular disease or those on heart-rate lowering meds. If Gilenya is considered needed, heart rates should be monitored at least overnight following the first dose. But all patients should have an electrocardiogram and blood pressure measured before a first dose and for six hours after treatment. And continuous ECG monitoring is recommended.
In reaching its decision, the FDA noted data show the maximum heart rate lowering effect usually occurs within six hours of the first dose, but the maximum effect may occur as late as 20 hours after the first dose in some patients (read the FDA statement and data summary here and the EMA report here). Despite these warnings, the FDA did not suggest that all Gilenya patients should be monitored overnight, which Wall Street viewed as a worst-case scenario because such a step would likely have inhibited more widespread usage.
Last month, the Institute for Safe Medicine Practices called on the agency to substantially restrict Gilenya usage and enhance patient monitoring after reviewing adverse events that were reported to the FDA during the second quarter of 2011, shortly after the drug was approved. The watchdog group also criticized the agency for placing Gilenya in its fast-track approval process.
Source: Pharmalot ©2012 UBM Canon Pharmaceutical Media Group (15/05/12)
New MS oral drug, Gilenya, still not available in Eire
A new oral drug to treat the symptoms of Multiple Sclerosis, which has been licensed and deemed cost-effective here, remains unavailable to sufferers.
The final stage in the HSE’s process before which it could be prescribed was “neither fair nor transparent”, a leading neurologist has said.
Prof Orla Hardiman, consultant neurologist at Beaumont Hospital in Dublin, said the MS drug Gilenya had been assessed and deemed cost-effective at the National Centre for Pharmacoeconomics (NCPE) in St James’s Hospital, Dublin.
Any pharmacological company seeking to have a new drug reimbursed for patients under the Community Drugs Schemes must first have its cost-effectiveness assessed by the centre.
Speaking on RTÉ radio yesterday, Prof Hardiman said the new drug was the first of a new generation of MS drugs that could be taken orally. “It looks like it’s going to be very effective.”
It would be prescribed to people already on injectable drugs for relapsing and remitting MS and for whom the drugs were not working effectively. Prof Hardiman said about 1,000 of the 6,000 or so MS sufferers here would benefit.
“It has been approved across Europe actually and we are one of the last countries where funding is a problem,” she said.
“There is a kind of a go-slow across the sector in terms of anything that might cost money.”
She said Gilenya would replace another drug so the extra cost would be “minimal”. There had to be a system that was “fair and transparent”.
“But the point at which drugs become available, when they reach the queue post the analysis, that’s not transparent . . . It’s not clear how the drug progresses from the top of the list into becoming available, and that’s a thing of grave concern to many of us in practice.”
There seemed to be another process, “whereby if you have an advocate, if you have a condition that generates a certain amount of sympathy through advocacy, that that’s the system to get the drug through”.
A spokeswoman for the HSE said there were a number of drugs, including for the treatment of MS, going through the process of approval. She said the assessment process was “well-established and has been in place for a number of years”.
Source: Irishtimes.com © 2012 irishtimes.com (08/05/12)
Gilenya positive benefit-risk profile following CHMP review, Europe
According to Novartis, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has confirmed a positive benefit-risk profile for their once-a-day orally administered drug Gilenya (fingolimod).
In agreement with the CHMP, the company has updated their E.U. product information after the Article 20 review the EMA announced in January 2012, in order to offer further guidance to healthcare providers who want to initiate using Gilenya in MS patients. In the E.U., Gilenya is approved for the treatment of individuals with highly active relapsing-remitting MS, regardless of treatment with beta interferon, or in patients with rapidly evolving severe relapsing-remitting MS.
Gilenya is the first in a new class of sphingosine 1-phosphate receptor (S1PR) modulating compounds and has demonstrated superior efficacy over Avonex (interferon-beta-1a IM), a commonly prescribed treatment. In a pivotal head-to-head trial in patients with relapsing- remitting multiple sclerosis at one year, Gilenya achieved both its primary and secondary endpoints, i.e. a 52% relative reduction of the yearly relapse rate and a 40% relative reduction in the rate of brain atrophy.
A recent sub-analysis at one year revealed that in comparison to interferon-beta-1a (IM), Gilenya achieved a 61% relative reduction in the rate of yearly relapses in patient subgroups with highly active relapsing-remitting MS patients who previously received interferon therapy.
Gilenya has no label restrictions specific to treatment duration and was generally well tolerated during clinical trials with a manageable safety profile. Since February 2012, over 36,000 patients have been treated with Gilenya in clinical trials and in the post-marketing setting, which confirms Gilenya's long- term effectiveness and safety profile. 2,400 patients have been taking the drug for longer than two years.
The most common adverse events reported were cough, diarrhea, headache, liver enzyme elevations and back pain, whilst other side effects included a mild increase in blood pressure, transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, macular edema, and mild bronchoconstriction.
Overall, the rates of infections, including serious events were similar in all treatment groups. However, patients treated with Gilenya reported a slightly higher rate of respiratory tract infections that consisted mainly of bronchitis. There were only a small number of reported malignancies in the clinical trial, with similar rates between the Gilenya and control groups.
All MS patients who start Gilenya therapy in the E.U. should have an electrocardiogram (ECG) and a blood pressure measurement before taking the first dose and after the six-hour first-dose monitoring period, in addition to having hourly measurements of their blood pressure and heart rate taken during this period. It is also recommended that patients' with symptomatic bradycardia (low heart rate) receive continuous ECG monitoring for at least six hours after taking the first dose, with those who had ECG abnormalities during the 6-hour monitoring period requiring extended monitoring, as well as those who had very low or their lowest measured heart rate at the six-hour time point.
The recommended label update in the E.U. also warns that Gilenya should not be used in patients who may be less tolerant of or tend to have a higher risk of developing a substantially slower or abnormal heart rate, due to certain underlying conditions or other medications taken at the same time.
Previous clinical trials have revealed insufficient knowledge about using Gilenya in such patients, but if these patients are to be treated, they would require overnight monitoring.
Patients who are already taking Gilenya are not affected by the new first-dose observation recommendations. However, should therapy be interrupted for longer than two weeks, patients should undergo the new recommended monitoring upon re-initiation of the treatment. Patients should not make any changes to any medications, including Gilenya, without first consulting with their doctor.
David Epstein, Division Head of Novartis Pharmaceuticals declares:
"We believe that Gilenya is a valuable treatment option for many patients with relapsing remitting MS, and we welcome the confirmation of the positive benefit-risk profile of the drug which also supports our continued belief of the blockbuster potential of Gilenya. MS is a devastating chronic disease that affects more than 2.1 million people worldwide, and patients need effective treatment options."
The EU will review the CHMP labeling recommendations, with a final decision expected in June 2012. In terms of any changes to the EU product information, Novartis will notify EU physicians via a Direct Healthcare Provider Communication (DHPC) by end of April 2012.
Source: Medical News Today © MediLexicon International Ltd 2004-2012 (24/04/12)
Updated prescribing data in USA for oral MS therapy Gilenya
Novartis says it has updated prescribing data for multiple sclerosis therapy Gilenya (Fingolimod) after a review by the Food and Drug Administration (FDA). The prescribing information includes new parameters for selecting patients, based on specific cardiovascular considerations. Novartis emphasizes that the prescribing information does not alter treatment management of MS patients currently taking Gilenya, unless treatment is stopped, and then a need to reinitiate occurs.
Gilenya (fingolimod) is an oral medication, taken once a day, which has been proven to reduce relapse numbers, as well as slowing down disability progression in patients with relapsing forms of MS (multiple sclerosis). Fingolimod, a sphingosine 1-phosphate receptor modulator, sequesters lymphocytes in lymph nodes, stopping them from becoming involved in an autoimmune reaction.
The prescribing information (PI) changes follow an FDA review, announced in December 2011.
The updated PI advises doctors to have patients who are being considered for Gilenya therapy to undergo an ECG (electrocardiogram) beforehand, and at the end of the six-hour observation period, as well as hourly heart rate and blood pressure measurements.
Novartis reiterates that patients currently already on Gilenya treatment are not affected by this update, unless they came off the medication and the doctor is considering restarting Gilenya therapy.
Novartis explains that new recommendations have been issued on how to reinitiate Gilenya therapy if it had been discontinued. If you are an MS patient, you should not make any changes to your current medication regime, even if you are on Gilenya, without checking with your doctor first.
The prescribing information also recommends that those with some pre-existing heart conditions, as well as patients on concomitant heart rate lowering drugs, be checked by a doctor before going on the first dose of Gilenya. If these patients then do go on to receiving Gilenya, they should be monitored overnight with continuous ECG in a clinic after the first dose. Novartis wrote on its US website today "Experience with the use of Gilenya in such patients is limited."
Gilenya contraindications
The term contraindications refers to when a treatment is inadvisable. The updated PI includes new contraindications.
Gilenya therapy is contraindicated in those with the presence of, or a history of:
Heart attack (during the last six months)
Stroke (during the last six months)
2nd and 3rd degree AV (atrioventricular) block
Other severe cardiac rhythm disturbances
As well as those taking certain anti-arrhythmic medications
Novartis informs that 36,000 patients globally have been treated with Gilenya in human studies in the post-marketing setting (as of February 2012).
Barry Singer, MD, Director, MS Center for Innovations in Care, Missouri Baptist Medical Center, said:
"Gilenya represents an important treatment option for relapsing forms of MS. Choosing appropriate patients for Gilenya therapy and patient safety is essential."
Novartis says it will be informing US doctors and patients through established field force and patient communication channels.
Source: Medical News Today MediLexicon International Ltd © 2004-2012 (23/04/12)
EU supports oral MS drug, Gilenya, with stronger warning
European regulators have endorsed the continued use of Novartis AG's multiple sclerosis pill Gilenya, one of the Swiss firm's top new drug hopes, but said on Friday the drug needed to carry stronger warnings on heart risks.
Novartis said the decision meant the drug remained on-track to be a "blockbuster" - one with annual sales above $1 billion.
Prospects for Gilenya, the first multiple sclerosis (MS) pill of its kind, have been clouded by reports of its association with serious heart problems.
The European Medicines Agency (EMA), which had initially aimed to give an update on Gilenya last month, said doctors should not prescribe it to patients with a history of cardiovascular and cerebrovascular disease or those on heart-rate lowering medication.
If treatment with Gilenya was considered necessary in these patients, however, their heart activity should be monitored at least overnight following the first dose of the drug, it said.
All patients getting the drug should have an electrocardiogram (ECG) and a blood pressure measurement prior to the first dose and after a six-hour initial period, during which continuous ECG monitoring is recommended.
A committee of EMA experts said the possible risk of heart problems could be limited by these stronger warnings.
"With these risk-minimization measures in place, the committee concludes that the benefits of Gilenya continue to outweigh the risks," the agency said in a statement.
David Epstein, head of Novartis Pharmaceuticals, said he welcomed EMA's confirmation of Gilenya's positive benefit-risk profile "which also supports our continued belief of the blockbuster potential of Gilenya".
WORST CASE AVOIDED
Analysts said there would be relief that the drug had not been pulled off the market but safety concerns would linger.
Martin Voegtli at Kepler Capital Markets said the strengthened warnings against prescribing in patients with cardiovascular risk factors would restrict the patient population and hit sales forecasts.
But Tim Race of Deutsche Bank viewed the EMA verdict more positively, since it ruled out the worse-case scenarios of either product removal or overnight monitoring for all patients.
Shares in Novartis were 0.6 percent higher at 1000 GMT, broadly in line with the European drugs sector.
Gilenya is still seen by analysts as a big seller, with annual sales of $1.7 billion by 2015, according to consensus forecasts collected by Thomson Reuters Pharma. But that is down on the $2.2 billion forecast in late 2011, due to safety fears.
In recent months, doctors have grown more cautious about the drug following reports of heart problems in some patients and the death of one person in the United States within 24 hours of starting treatment.
Those cases prompted the EMA to start its review in January, when it first advised doctors to continuously monitor patients for six hours after giving them a first dose. The U.S. Food and Drug Administration (FDA) is also looking into the drug.
Gilenya represents a significant change in MS treatment, since existing medicines like beta interferons and Elan and Biogen Idec's Tysabri must be injected.
Rival oral MS treatments in development include BG-12 from Biogen, teriflunomide from Sanofi and laquinimod from Teva.
Source: Reuters (c) Thomson Reuters 2012 (20/04/12)
Extension study data for Gilenya® shows patients successfully treated for up to 7 years
New data will be presented at the 64th annual meeting of the American Academy of Neurology (AAN) that support the efficacy and safety profile of Gilenya® (fingolimod), the only oral therapy approved to treat relapsing forms of multiple sclerosis (MS).
"The data being presented reinforce our confidence in the sustained efficacy and safety profile of Gilenya," said David Epstein, Head of the Pharmaceuticals Division of Novartis Pharma AG.
New data presented on long-term efficacy and safety profile of Gilenya.
New results from the phase III FREEDOMS extension study showed significant improvements in clinical and MRI measures in patients who switched from placebo (administered during the 24-month core study) to Gilenya (administered during the extension).
1033 patients completed the two-year, double-blind FREEDOMS 24 month core study. Of these, 90% of patients completed 3 years observation and 45% were followed for 4 years in this study before being transferred to the umbrella follow-up study (LONGTERMS).
Patients who switched from placebo to Gilenya saw a 55% decrease in their annualized relapse rate (ARR) during the extension phase compared to the core phase (ARR [core] = 0. 29 vs. ARR [extension] 0.13; p<0.001). Significantly more patients on continuous fingolimod treatment compared to those first randomized to placebo remained relapse-free (59% vs. 37%) and free from three-month confirmed disability progression (74 % vs. 66 %).
MRI measures continued to show significant effects in favor of fingolimod treatment, including a significantly reduced rate of brain atrophy in the patients treated continuously as compared to switch patients (mean (%) change in brain volume -1.67% vs. -2.24%; p = 0.001) at the end of the observation. In the core FREEDOMS study, Gilenya reduced the rate of brain atrophy by 38% versus placebo at two years (0-24 months).
The phase III FREEDOMS extension showed a safety profile consistent with that of the pivotal phase III trials. The most common adverse events were nasopharyngitis, low lymphocyte counts (to be expected from the mode of action), upper respiratory tract infections and influenza.
"This extension study confirms the efficacy shown in the published phase III studies and supports the positive long term impact of continuous treatment. The favorable longer term safety profile is consistent with results from the phase III studies," said Ludwig Kappos, Department of Neurology, University of Basel, Switzerland. "These observations in a large group of patients, now for four and more years, confirm that fingolimod is a valuable treatment option for patients with relapsing remitting MS."
Additionally, new data for up to 7 years of treatment from the phase II extension study demonstrated patients treated with Gilenya (n=122) had sustained low MRI and clinical disease activity. The overall ARR for the continuous Gilenya treatment group was 0.16, which can be expressed as one relapse every 6 years. Of patients on continuous Gilenya treatment since study start and who completed the long-term extension, over half had remained free of relapses throughout the study.
The phase III registration program for Gilenya included the two-year FREEDOMS study and a head-to-head study in which Gilenya showed a 52% relative reduction in annualized relapse rate (primary endpoint) compared to Avonex® (interferon-beta-1a IM), a commonly prescribed treatment, at one year.
Low incidence of ECG abnormalities and symptomatic heart rate reduction at treatment initiation in 2,400 patient FIRST Study
New data from the large, 4-month, open-label, single-arm multi-center FIRST study demonstrate an overall low incidence of significant first dose bradycardia [i.e. 1.3% of patients experienced bradycardia < 45 bmp and no patient experienced a heart rate
Source: Market Watch Copyright © 2012 MarketWatch, Inc (20/04/12)
EU to rule on safety of Novartis's Gilenya MS pill
Europe's drug regulator will likely allow Novartis AG's Gilenya to stay on the market without asking for much stricter safety warnings as it concludes a review of the multiple sclerosis pill initiated after reports of heart problems and the death of a patient who took the drug.
The regulator's decision could come as early as Thursday, said the London-based European Medicines Agency, the body responsible for licensing Gilenya in Europe a year ago.
The EMA launched the in-depth study in January to assess Gilenya's benefits and risks, and recommended doctors closely monitor the hearts of patients after they have been given the first dose of the drug.
The review was prompted by reports of heart problems in patients taking Gilenya, as well as the November death of a 59-year-old patient in the U.S. less than 24 hours after taking the first dose of the drug. The EMA had aimed to give an update on Gilenya's safety in March, but delayed its decision by about a month as it finalises its review.
The U.S. Food and Drug Administration also announced a safety review of Gilenya in December, saying there wasn't a clear cause of the patient's death. There is no time frame for the FDA's review.
Analysts say it is unlikely that Gilenya will be withdrawn from the market or that the EMA will request changes to the drug's label, which already warns of cardiovascular side effects.
"This is a drug that has already been well-studied during clinical trials, and side effects have already showed up," said David Kaegi, an analyst with Bank Sarasin in Zurich. "I am optimistic that nothing will change--the drug has been on the market for a while already," said Kaegi, who has a buy rating on Novartis.
The Swiss company said in a statement that it continues to believe that the drug provides a benefit for patients with relapsing-remitting multiple sclerosis and added that it is "engaging with the EMA, other health authorities and the MS community with the goal of ensuring that appropriate patients will have access to Gilenya."
Gilenya is one of Novartis' most promising new drugs and has looked like becoming one of the leading treatments in the multibillion-dollar market for treating MS due to its easy use. Unlike traditional MS treatments that are given via infusions or injections, Gilenya is administered in pill form--the only one to date.
Gilenya has been available in the European Union since March 2011 for treating relapsing-remitting MS, the most common type of the disease, in patients who have failed to respond to a beta-interferon or whose condition is severe and worsening rapidly. The drug was approved in the U.S. in 2010.
Source: Market Watch Copyright © 2012 MarketWatch, Inc (18/04/12)
Oral MS drug Gilenya patient develops rare brain disease
Novartis AG said a patient treated with its multiple-sclerosis pill Gilenya has been diagnosed with a rare and often fatal brain disease.
The Swiss drug maker said the patient had been previously treated with another MS drug, Tysabri, co-marketed by Biogen Idec Inc. and Elan Corp. PLC, which has been already associated with progressive multifocal leukoencephalopathy.
"The current assessment is that Tysabri is the drug most likely associated with this case of PML," Novartis said in a statement. "However, a contribution of Gilenya to the evolution of this case cannot be excluded."
The development comes at a critical time for Novartis's Gilenya, a potential blockbuster product whose safety profile has recently come into question after the death of one person in the U.S. last autumn within 24 hours of starting treatment.
The European Medicines Agency, the body responsible for licensing Gilenya in Europe a year ago, is expected to issue a decision on the safety of the medicine following an in-depth review next week.
Novartis said it doesn't know of any confirmed PML cases in patients treated with Gilenya, also known as fingolimod, who hadn't previously been treated with Tysabri.
Novartis statement: Gilenya (fingolimod) safety information update
April 13, 2012
Novartis has been informed of a progressive multifocal leukoencephalopathy (PML) diagnosis in a JCV antibody positive MS patient who had previously been treated with Tysabri® (natalizumab) for approximately three and a half years prior to initiating treatment with Gilenya (fingolimod).
There is a known risk of PML associated with natalizumab treatment, especially in patients who are JCV antibody positive and have been treated with natalizumab for more than two years. The current assessment is that natalizumab is the drug most likely associated with this case of PML. However, a contribution of Gilenya to the evolution of this case cannot be excluded.
This is the first reported PML case in approximately 36,000 fingolimod-treated patients, of whom approximately 2,400 were treated for more than two years and approximately 500 were treated for more than four years. There is currently no confirmed case of PML reported to Novartis in a fingolimod-treated patient without previous natalizumab treatment.
Details on the case are being submitted to health authorities according to regulations as they become available.
Novartis believes Gilenya is a benefit for appropriate MS patients when used in accordance with approved labeling.
Source: 4 - Traders Copyright © 2012 Surperformance & Novartis (13/04/12)
Watchdog group wants restrictions on Gilenya for MS
The Institute for Safe Medication Practices (ISMP) is urging the US Food and Drug Administration (FDA) to put restrictions on the use of fingolimod (Gilenya, Novartis) in patients with multiple sclerosis (MS), owing to postmarketing adverse event reports.
"Problems of widespread toxicity that were already evident in clinical testing of fingolimod are now producing strong signals in the postmarket adverse event data," the nonprofit group says in a new report.
The ISMP sifted through adverse event reports related to fingolimod that were reported via the FDA's MedWatch program in the second quarter of 2011.
"Notable" among them, they say, are 68 reports of serious infections, including eye, skin, urinary, and upper respiratory tract infections. Sixty eye-related side effects were also reported, including macular edema and vision disruptions.
In 14 cases, patients taking the drug experienced more generalised symptoms, including heart-rhythm problems and liver damage, the report states. Possible complications of these vascular adverse effects include syncope (16 cases), bradycardia (27 cases), and peripheral edema (10 cases), the report notes.
"The signals for fingolimod raise the question whether enough is known about the troubling safety profile of this drug to justify its continued unrestricted use. Its array of known adverse effects on the eyes, heart, liver, and immune response, as well as patient deaths in testing and postmarket surveillance, raise the question about its long-term use at the current approved dose," the ISMP concludes.
The report urges the FDA and manufacturer to "consider substantial restrictions on its use and enhanced monitoring" of patients using it.
Drug Currently Under Review
Fingolimod is the first oral agent for the treatment of MS. It was approved by the FDA in September 2010 and by the European Medicines Agency (EMA) in March 2011. However, the occurrence of the death of a patient soon after receiving a first dose of fingolimod in December 2011 has both the FDA and the EMA looking closely again at the risks and potential benefits of fingolimod. Those reviews are still under way.
Asked for reaction to the ISMP report, Timothy Coetzee, MD, Chief Research Officer of the National MS Society, told Medscape Medical News: "The FDA has already announced that it is reviewing the safety profile of Gilenya. We are following the matter closely and waiting to see the results of their investigation. Therefore, we feel that it would be somewhat premature to comment in advance of the release of the FDA findings, which we anticipate will be forthcoming soon."
Source: Medscape Copyright © 1994-2012 by WebMD LLC (11/04/12)
Relapse and disability outcomes in patients with MS treated with fingolimod
Subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study
Summary
Background
Fingolimod 0·5 mg once daily is approved for treatment of relapsing multiple sclerosis (MS). In the phase 3, 2-year FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in MS) study, fingolimod significantly reduced annualised relapse rates (ARRs) and the risk of confirmed disability progression compared with placebo. We aimed to investigate whether the beneficial treatment effect reported for the overall population is consistent in subgroups of patients with different baseline characteristics.
Methods
We did subgroup analyses of ARRs (primary outcome) and confirmed disability progression (a secondary outcome) over 24 months in the FREEDOMS study, a randomised, double-blind study that included 1272 patients with relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0·5 mg or 1·25 mg) or placebo once daily for 24 months. Subgroups were predefined, predefined and slightly modified, or defined post hoc, by demographic factors (including sex and age), disease characteristics (including baseline disability scores, relapse rates, and lesion parameters), and response to previous therapy (including analyses in patients eligible for fingolimod treatment according to the European label). Data were analysed by intention to treat. The FREEDOMS study is registered with ClinicalTrials.gov, number NCT00289978.
Findings
Treatment with fingolimod 0·5 mg was associated with significantly lower ARRs versus placebo across all subgroups except for patients aged over 40 years. ARR ratios ranged from 0·76 (95% CI 0·54—1·09; p=0·13) in patients aged over 40 years to 0·29 (0·16—0·52; p<0·0001) in patients who had relapse activity despite receiving interferon beta during the year before study enrolment. Hazard ratios for confirmed disability progression over 24 months with fingolimod 0·5 mg versus placebo ranged from 0·85 (95% CI 0·53—1·36; p=0·50) in patients with a T2 lesion volume of 3300 mm3 or less to 0·32 (0·14—0·73; p=0·0066) in patients with an EDSS over 3·5. In patients who relapsed and had lesion activity despite treatment with interferon beta in the previous year, the ARR ratio for fingolimod 0·5 mg versus placebo was 0·38 (95% CI 0·21—0·68, p=0·0011), and for treatment-naive patients with rapidly evolving severe disease it was 0·33 (0·18—0·62, p=0·0006). Hazard ratios for confirmed disability progression over 24 months were 0·68 (0·29—1·62; p=0·39) and 0·73 (0·25—2·07; p=0·55), respectively, in these groups.
Interpretation
Patients with relapsing-remitting MS with a wide spectrum of clinical and MRI features including subgroups specified by the European label can potentially benefit from treatment with 0·5 mg fingolimod.
Funding
Novartis.
Virginia Devonshire MD, Eva Havrdova MD, Prof Ernst Wilhelm Radue MD, Paul O'Connor MD, Lixin Zhang-Auberson MD, Catherine Agoropoulou PhD, Dieter Adrian Häring PhD, Gordon Francis MD, Prof Ludwig Kappos MD
Source: The Lancet Neurology doi:10.1016/S1474-4422(12)70056-X Copyright © 2012 Elsevier Limited (10/04/12)
Calls for oral MS treatment, Gilenya, to be made available in Ireland
The Multiple Sclerosis Society of Ireland (MS Ireland) has called on the government to make available in Ireland a controversial drug that it believes would much more effectively treat some forms of the disease.
The call, echoed by the drug’s manufacturer, follows the decision by the National Institute for Health and Clinical Excellence (NICE) in the UK to recommend that the drug, fingolimod - known by its brand name Gilenya - , be available on the National Health Service (NHS) for some patients with a form of MS.
It comes less than two months after a European Agency opened an investigation in to whether the medicine played a role in the deaths of at least 11 patients. The European Medicines Agency (EMA) is due to give an update on the safety of the medicine next month, the Wall Street Journal reports.
The Department of Health said that the matter was being considered by the Health Service Executive (HSE) which said that it expects “a significant budget impact with this product” if its use in treatment could be reimbursed under the High Tech Drug Scheme as MS Ireland wants.
The manufacturer, Novartis, claims that the drug is twice as effective as conventional treatment for the disease which affects some 8,000 people in Ireland. The drug itself was authorised by the Irish Medicines Board exactly a year ago and there has been no updated guidance in relation to it since.
Multiple Sclerosis
MS is an autoimmune disease which affects the brain and spinal cord. It generally affects women more than men and is more likely to affect people who have a family history of the disease.
NICE said that the treatment was a “valuable, innovative and cost-effective therapy” for dealing with highly active relapsing-remitting MS which is characterised by periods where symptoms – which include numbness, tingling, blurred vision, balance problems and muscle weakness – worsen and then improve.
This particular oral medication, manufactured by Novartis, will now likely be available to people in England and Wales through the NHS. Novartis said that steps are also being taken by healthcare systems in most EU countries to make it available. Much may hinge on the updated guidance of the EMA next month following its investigation.
However, Novartis claimed that the Department of Health had decided not to make it available to Irish patients despite it being given a positive review by the National Centre for Pharmacoeconomics (NCPE) last year.
“Novartis has submitted a proposed price as part of the high tech application process. At the price submitted the NCPE considered Gilenya ‘a cost effective therapy for the treatment of relapsing remitting multiple sclerosis patients in the Irish healthcare setting’,” a statement said.
“The price is not out of line with other European countries already reimbursed, and is within the range of disease modifying therapies in the Irish market (including VAT).”
‘Significant budget impact’
However the HSE said in a statement: “The HSE has approved – and continues to approve – all medicines for which it believes there is robust evidence that they are cost effective and budget neutral.
The HSE expects a significant budget impact with this product and is currently considering how new medicines can be introduced into clinical care pathways as and when HSE resources become available.
The HSE is working to ensure that all appropriate arrangements and controls are in place to support optimal use and that best value is achieved.”
MS Ireland called on the the government to make it available for patients on long-term treatment plans in Ireland.
“MS Ireland believes that this disease modifying therapy would be an important addition to the choice of treatments available to people with MS,” chief executive Ava Battles said.
“It is not acceptable that people with MS in Ireland have less choice of treatments that are capable of modifying the progress of their illness than counterparts in Britain and other EU countries.
“We have written to the Minister and the Department on this matter and anticipate it will be treated as a matter of urgency.”
Source: The Journal.ie © Journal Media Ltd. 2012 (19/03/12)
Scottish MS Society will challenge Gilenya decision
Multiple sclerosis campaigners will step up their bid to persuade Scotland’s medicines regulator to overturn its decision to reject a new treatment for the disease.
The Multiple Sclerosis Society Scotland yesterday said it would be writing to the Scottish Medicines Consortium (SMC) to try to convince the regulator it should approve the use of fingolimod.
Pressure mounted on the SMC after its equivalent body south of the Border, the National Institute for Health and Clinical Excellence (NICE), approved the drug in England and Wales.
The production of draft NICE guidance recommending the use of fingolimod has raised the prospect of a north/south divide opening up when it comes to treating the disease.
Yesterday Craig Wilkie, MSSS head of policy, said that the charity would also be lobbying MSPs on the issue.
A SMC spokesman said: “We are always happy to hear interest groups’ points of view and we would be happy to hear from the MSSS.”
Source: Scotsman.com © 2012 Johnston Publishing Ltd (19/03/12)
NICE backs new oral MS drug, Gilenya
Novartis's multiple sclerosis pill Gilenya has been recommended for use on the U.K.'s publicly-funded National Health Service after a change of heart by the country's healthcare cost-effectiveness watchdog.
Friday's verdict from the National Institute for Health and Clinical Excellence, whose opinions are also watched closely in other countries, is welcome news for the Swiss company's potential blockbuster product whose safety profile has come into question recently.
NICE said it changed its mind on the medicine, also knows as fingolimod, after Novartis provided more information and analyses on the pill, allowing the British agency to compare the medicine's performance with existing injectable MS therapies.
"The latest draft guidance from our committee recommends the NHS-use of fingolimod for a specific group of adults who have highly active relapsing-remitting multiple sclerosis," said Carole Longson director of the Health Technology Evaluation Centre at NICE.
"Following new information provided during the consultation, the analyses show that for these people, treatment with fingolimod will be a cost effective option for the NHS in this group of people with multiple sclerosis, if Novartis provides the drug at a discounted price, as proposed in its patient access scheme."
The Swiss drug maker applauded the move by NICE, adding: "Novartis believes that Gilenya is generally a highly efficacious and cost-effective treatment for patients with relapsing-remitting multiple-sclerosis and remains committed to engaging with reimbursement authorities with the goal of ensuring that appropriate patients will have access to the treatment."
Gilenya was licensed in Europe a year ago and has now been approved in more than 55 countries, with more than 25,000 patients having been prescribed it so far.
But EU regulators are conducting a review of the MS pill in light of reports of heart problems in some patients and the death of one person in the U.S. last autumn within 24 hours of starting treatment.
Campaigners have urged Scotland's medicines regulator to reverse a decision to reject a new drug for patients with MS after the equivalent body south of the Border approved the same pill.
The Scottish Medicines Consortium (SMC) said the makers of fingolimod, the first tablet treatment for MS, did not show it was good value for money and the body chose not to recommend it for use on the NHS.
But now the National Institute for Health and Clinical Excellence (Nice), which rules on drugs in England and Wales, has revealed draft guidance recommending fingolimod, whose brand name is Gilenya, for prescription on the NHS for some patients with relapsing-remitting multiple sclerosis.
It raises the prospect of a north-south divide for patients, even although Scotland suffers the highest rate of MS in the world, with 10,500 people diagnosed with the condition.
Dr Belinda Weller, a neurologist at the Western General in Edinburgh who led the Scottish clinical trial of fingolimod, said: "It's going to be quite hard for our patients in Scotland who are aware that people over the Border are going to be having access to this.
"But I'm also hopeful that with that decision there will be more pressure on the regulatory body in Scotland to reconsider the decision."
Fingolimod can help reduce the number of relapses in adults with relapsing-remitting multiple sclerosis.
A spokesman for the SMC said: "Sometimes SMC has to make very difficult decisions and we are acutely aware that our decisions have an impact on patients."
Source: Market Watch Copyright © 2012 MarketWatch, Inc. & Herald Scotland © Copyright 2012 Herald & Times Group(16/03/12)
Scottish Medicines Consortium (SMC) turns down oral MS drug Gilenya
The Scottish Medicines Consortium (SMC) yesterday rejected recommending the prescribing of the first oral pill for sufferers of multiple sclerosis in Scotland.
The SMC said that, while the manufacturers of Gilenya, had provided evidence about it helping to reduce relapse rates, they had not compared it with another drug commonly used in Scotland.
It added that evidence showed that starting treatment with Fingolimod could cause a short-term decrease in heart rate and swelling of the centre of the retina inside the eye, and that about half the patients developed infections. The SMC concluded that it did not consider the drug to be “value for money” for the NHS in Scotland.
Novartis launched Fingolimod in the UK in April 2011, but the National Institute for Health and Clinical Excellence (NICE) recommended in December that Fingolimod was not a cost effective treatment for the NHS in England and Wales to provide.
Fingolimod works by acting on certain types of white blood cells (lymphocytes) which are involved in the immune attack that characterises MS, which results in the destruction of myelin, the substance covering and protecting nerves in the central nervous system.
It effectively reduces the number of lymphocytes circulating in the blood, resulting in reduced immune attack on nerve cells in the brain and spinal cord.
In addition, there is evidence that Fingolimod may have a direct effect on nerve cell damage and enhance re-myelination.
In March last year, the European Medicines Agency (EMA) approved Fingolimod as a second-line treatment to be used if people continue to have relapses or if their relapse rate has increased despite a year’s treatment with one of the first line drugs.
It can also be used with people with rapidly evolving severe relapsing remitting MS – two or more relapses a year.
Scotland has one of the highest rates of MS in the world, with 10,500 diagnosed cases. The debilitating disease attacks the central nervous system, with current treatment consisting of intermuscular injections or infusion therapy.
Last night, Dr Belinda Weller, a consultant neurologist who took part in clinical trials, said: “Today’s decision is very disappointing, as we’ve waited a long time for the first pill to treat this disabling condition effectively.”
Novartis has asked the SMC for further clarification.
Source: The Scotsman © 2012 Johnston Publishing Ltd (13/03/12)
Scottish decision due on oral MS drug Gilenya
The Scottish Medicines Consortium (SMC) will decide on today if it will recommend the prescribing of the first oral pill for the treatment of Multiple Sclerosis in Scotland.
Currently, suffers face painful daily injections deep into the muscle or having to travel to hospital for infusion therapy to try to control the disease, which damages the central nervous system, causing a range of disabilities such as problems with co-ordination, speech and vision.
But this treatment could be consigned to the past for thousands of sufferers north of the Border if the SMC gives the go-ahead for the drug Gilenya, the world’s first licensed pill for the condition.
Sufferers would instead take a daily pill estimated to halve the chances of a relapse.
Scotland has one of the highest rates MS in the world with around 10,500 cases diagnosed. Research indicates genetic factors may play a role. The disease is mostly diagnosed in people aged between the ages of 20-40 and affects almost twice as many women than men.
The drug is targeted at those suffering the most common form of the disease which is “relapsing and remitting”, characterised by exacerbations or flare-ups interspersed with remission.
Nick Rijke, director of policy and research at the MS Society, said: “We’re expecting the Scottish Medicines Consortium to make their final decision on Fingolimod imminently. This treatment has the potential to benefit thousands of people living with MS in Scotland. We would therefore like to see it become available to all those who could benefit.”
Fingolimod, also known as “Gilenya”, is an immunosuppressant which works by keeping lymphocytes (a type of immune cell) sequestered in the lymph nodes. This reduces the number of lymphocytes reaching the brain and spinal cord where they might attack the coating of the nerve cells.
The annual cost of treating one patient with Fingolimod is estimated at £19,665, compared with £21,257 for Natalizumab, used in monthly infusions. Relapses requiring hospitalisation cost the NHS more than £3,000 per episode.
The drug, already approved in 35 countries, including the US, Canada and Germany, was licensed in the UK last April meaning health officials recognised that it was “relatively safe and did something beneficial for a particular ailment”.
However, the vital decision for sufferers in Scotland, to be announced on Monday afternoon, is whether Fingolimod can be prescribed across all health boards in Scotland making it routinely available to patients.
Currently, clinicians can request funding on a case-by-case basis for individual patients subject to approval by their hospital trust.
A limited number of patients in the UK, chosen to be part of pilot studies, have also had access to Fingolimod.
A spokesman for the SMC said: “We can confirm that our decision on Fingolimod will be announced on Monday afternoon.”
The National Institute for Health and Clinical Excellence, the medicines regulatory body for England, is due to announce its decision on the drug, the following week.
Source: The Scotsman © 2012 Johnston Publishing Ltd (12/03/12)
Deaths hit oral MS drug, Gilenya
Novartis AG's Gilenya multiple sclerosis pill lost market share for the first time in January, following the deaths of some patients soon after taking the first pill available for the disease in the United States.
Gilenya's share of the U.S. market for so-called immunomodulatory drugs against MS fell to 6.1 percent from 6.2 percent in December, according to data from Wolters Kluwer NV, a market research company. The decline was the first after 15 months of growth, at a median of 15 percent a month, since the treatment received U.S. regulatory approval in September 2010.
The Food and Drug Administration and the European Medicines Agency are investigating 11 deaths among Gilenya patients. In the past month, analysts have cut their forecasts for peak sales of Gilenya by 10 percent to $2.1 billion in 2016, according to the average of six estimates compiled by Bloomberg.
The deaths have "made me a little more cautious," said Aaron Miller, chief medical officer of the U.S. National Multiple Sclerosis Society, and a medical director at Mount Sinai Hospital in New York. "I am not somebody who has recommended Gilenya as a first-line drug prior to these reports, and I'm still not recommending it as a first-line drug until we get more data."
Source: SF Gate © 2012 Hearst Communications Inc (07/03/12)
Safety of oral MS pill Gilenya reviewed after deaths
Health Canada is reviewing a new multiple sclerosis drug that has been linked to 11 deaths.
There have been no reports of deaths in Canada of people taking the Novartis drug, which is sold under the brand name Gilenya.
Health Canada says that of the deaths outside the country, it's not clear whether the drug itself caused them, or whether other factors played a role.
Both the U.S. Food and Drug Administration and the European Medicines Agency had earlier announced that they were undertaking reviews of Gilenya.
Gilenya is used for treatment of relapsing-remitting MS to reduce the frequency of attacks and to delay physical disability; it is generally recommended when other MS treatments have not been effective or cannot be tolerated.
At the time the drug was authorized, it was known that certain types of heart rhythm disturbances can be seen with Gilenya use and the Canadian labelling contains several warnings to this effect.
But Health Canada says it felt the drug's benefits outweighed its risks.
Of the 11 reported deaths, four involved serious heart-related events — three were heart attacks and another a disturbance of the heart rhythm. The seven other deaths are unexplained, including one from the United States involving a person who died within 24 hours of his or her first dose of Gilenya.
Health Canada says people taking the drug should not discontinue it without consulting their doctor. But anyone on the drug who is feeling symptoms of heart disease — including chest pain, slow or irregular heartbeat, or dizziness — should seek medical care.
The department says doctors should monitor patients on the drug closely. Blood pressure should be checked regularly as the drug is known to increase blood pressure.
Source: CBC News © The Canadian Press, 2012 (28/02/12)
A randomized, controlled trial of fingolimod (FTY720) in Japanese MS patients
Abstract
Background: Fingolimod (FTY720) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian populations with multiple sclerosis (MS).
Objectives: To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod.
Methods: In this double-blind, parallel-group, phase II study, 171 Japanese patients with relapsing MS were randomized to receive once-daily fingolimod 0.5 mg or 1.25 mg, or matching placebo for six months. The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6, and relapses over six months, respectively; safety outcomes were also assessed.
Results: 147 patients completed the study. Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod (0.5 mg: 70%, p = 0.004; 1.25 mg: 86%, p < 0.001) than with placebo (40%). Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant. Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation, and elevated liver enzyme levels.
Conclusions: This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS, consistent with the established effects of fingolimod in Caucasian patients.
Saida T, Kikuchi S, Itoyama Y, Hao Q, Kurosawa T, Nagato K, Tang D, Zhang-Auberson L, Kira J.
Dept of Neurology, Kyoto Min-Iren-Central Hospital/Institute of Neurotherapeutics/Kyoto University Hospital, Kyoto, Japan.
Source: Pubmed PMID 22354739 & Mult Scler. 2012 Feb 21 Copyright © 2012 by SAGE Publications (27/02/12)
EU says MS drug Gilenya needs heart monitoring
The European Medicines Agency advised doctors to continuously monitor patients for six hours after giving them a first dose of Novartis AG's multiple sclerosis drug Gilenya, casting a shadow over the potential blockbuster product.
The move came as the organisation started a review into the safety of the medicine, following reports of heart problems in patients and the death of one person in the United States within 24 hours of starting treatment.
The Swiss drugmaker said last month it was investigating whether Gilenya, seen by analysts as a potential multibillion-dollar seller, caused the death of the 59-year-old U.S. patient.
Gilenya can temporarily slow the heart rate. Although this usually returns to normal after a few hours, the European watchdog recommended intense cardiovascular monitoring after the first dose.
This should include electrocardiogram (ECG) monitoring before treatment and then continuously for the first six hours afterwards, as well as measurement of blood pressure and heart rate every hour.
Mark Schoenebaum, an analyst at ISI Group, said the call for active ECG monitoring was very different from the U.S. Food and Drug Administration (FDA) recommendation of observation and could encourage European doctors to use Biogen Idec's experimental BG-12.
"We believe active ECG monitoring for six hours could be a material impediment to starting patients on Gilenya and could enhance BG-12's attractiveness to EU physicians once approved," he said.
The FDA said on December 20 it was also looking into the U.S. case. Regulators on both sides of the Atlantic said the exact cause of the patient's death was still unexplained.
Novartis was not immediately available for comment.
SPOOKY PROSPECT
"It's a bit early to draw too many conclusions on the basis of just one case, but if this keeps happening and serious cardiovascular problems turn out to be an issue, then this will definitely spook doctors," Vontobel analyst Andrew Weiss said.
European authorities approved Gilenya last March for people with highly active relapsing-remitting multiple sclerosis (RRMS), the commonest form of the debilitating disease.
More than 30,000 people have received the drug worldwide.
Novartis is banking on the success of its newest drugs, such as Gilenya, to help it protect its top and bottom lines as established medicines lose patent protection and face competition from cheaper copies.
Analysts, on average, forecast annual sales of $1.8 billion by 2016, according to Thomson Reuters Pharma.
Gilenya is likely to face increased competition as other drugmakers such as Biogen and Sanofi push ahead with their latest MS medicines.
Some experts have tipped Biogen's BG-12 to become the world's leading treatment for multiple sclerosis, while Sanofi's Genzyme unit plans to submit Lemtrada for approval in the United States and Europe in the first quarter of 2012.
BG-12's key competitive advantage may lie in its safety profile, which looks relatively clean based on two-year data, analysts have said.
Multiple sclerosis affects 2.5 million people worldwide and is a chronic, often disabling disease that attacks the central nervous system and can lead to numbness, paralysis and loss of vision.
Source: Reuters © Thomson Reuters 2012 (23/01/12)
Oral MS drug Gilenya reviewed by EU after 11 patient deaths
The European Medicines Agency started a review of Novartis AG’s Gilenya pill for multiple sclerosis after 11 deaths among patients who received treatment.
The reports raise concern that the drug, the first oral medicine for the debilitating neurological disease, may harm the heart, the London-based agency said in an e-mailed statement today. Eric Althoff, a spokesman for Novartis in Basel, Switzerland, didn’t immediately return a call and e-mail requesting comment.
Novartis said last month a patient died Nov. 23 after starting treatment with Gilenya. Ten other deaths have been reported among patients who began taking Gilenya, including six unexplained deaths, three heart attacks and one due to disruption of heart rhythm, the agency said today. It isn’t clear what role if any Gilenya had in the deaths, EMA said.
“In my view this is highly unlikely to be related to the drug, but of course they have to check that,” Karl Heinz Koch, an analyst at Helvea SA in Zurich, said in a telephone interview today. “With all the experience we have with the drug, my comfort level is relatively high, but you can never be 100 percent sure. It certainly doesn’t help the share price.”
Novartis fell 1.5 percent to 53.40 Swiss francs as of 12:21 p.m. in Zurich trading, after rising as much as 0.6 percent earlier in the session.
First MS Pill
Gilenya was approved in the U.S. in 2010 as the first oral treatment for multiple sclerosis, and cleared for sale in Europe in March. It’s among the products Novartis is depending on to boost sales as patents start to expire on the company’s best- selling drugs, including the hypertension pill Diovan.
Biogen Idec Inc. plans to submit its oral MS drug, called BG-12, to regulators during the first half of this year after it was safe and effective in a late-stage trial, the Weston, Massachusetts-based company said in October.
“Increased alertness to toxicities is not what Novartis needs,” said Andrew Weiss, an analyst at Bank Vontobel AG in Zurich, in an e-mail. “Will the tox profile become Gilenya’s Achilles heel?”
The risk of slow heart rate, or bradycardia, after the first dose was known when the drug was approved, EMA said. The agency’s committee on human medicines expects to complete its review in March, the regulator said.
Doctors should increase patient monitoring after the first dose is given, the EMA said. That includes electrocardiograms before treatment and for the first six hours after the first dose, and then checking blood pressure and heart rate every hour, the EMA said. After six hours, patients with a slow heart rate or problems with electricity conduction in the heart should be watched until their condition has improved.
More than 30,000 patients worldwide have now taken the medicine, according to the EMA statement.
Source: Bloomberg ©2012 Bloomberg L.P (20/01/12)
