The FDA is continuing to investigate a possible link between the multiple sclerosis drug Gilenya (fingolimod) and a case of a rare brain infection in a European patient.
The patient took the drug for nearly 8 months before being diagnosed with the brain infection. The FDA issued an alert at the end of August to inform the public of its investigation.
The brain infection, sometimes fatal, is called PML (progressive multifocal leukoencephalopathy). The European case is the first reported in a patient who has not previously taken the drug Tysabri (natalizumab). Tysabri is already known to be linked with a higher risk for PML.
The maker of Gilenya, Novartis, issued a statement saying it had reviewed all available evidence and that the case of PML in Europe is unlikely to be linked to the drug.
Gilenya, approved by the FDA in 2010 for relapsing MS, is taken by mouth. It is one of three new oral drugs approved in the last 3 years. The other two are Tecfidera (dimethyl fumarate) and Aubagio (teriflunomide).
In MS, the immune system attacks the central nervous system, including the brain, spinal cord, and optic nerves.
According to the FDA, patients should not quit taking Gilenya without talking to their doctor.
The FDA will issue its findings once the investigation is complete.
Source: WedMD ©2005-2013 WebMD, LLC. (21/10/13)
Novartis announced today findings from an international multiple sclerosis (MS) registry and a US health claims data base which showed the real-world superiority of Gilenya® (fingolimod) in reducing risks of relapses compared to standard therapies. These data confirm the positive results seen in clinical trials with Gilenya, and were presented at the ongoing 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark.
Relapses can make life unpredictable for patients with MS and they can potentially significantly advance an individual's level of disability. MS patients' clinical outcomes are regularly assessed and switching between disease-modifying therapies (DMTs), to reduce the rate or likelihood of a relapse, is a frequent treatment strategy.
"Controlling relapses and preventing disability are key treatment goals for patients with MS." said David Epstein, Division Head of Novartis Pharmaceuticals. "It is encouraging to see that the benefits of Gilenya, which is the only disease modifying treatment proven in clinical studies to have a superior relapse reduction compared to an active comparator, are now confirmed in the real-world setting."
The 'MSBase study', a global, longitudinal, observational registry for MS involving 60 centers in 26 countries and US administrative claims data from the 'IMS PharMetrics PlusTM Database' were interrogated for information on the impact on MS relapses of switching to either oral Gilenya or to one of the standard injectable therapies - an interferon or glatiramer acetate. Collectively, analysis of patient data from these large, real-world databases (416 patients from MSBase and 933 patients from the IMS PharMetrics PlusTM Database) showed that treatment with Gilenya reduced the annualized relapse rate and risk of relapse by approximately 50% compared to therapy with an interferon or glatiramer acetate treatment. They also showed that even amongst patients with MS who have a history of relapse, switching to Gilenya was associated with significant and clinically meaningful reductions in the number of relapses and the probability of experiencing a relapse compared to switching to an interferon or glatiramer acetate.
Following first approvals in 2010, once daily oral Gilenya is now available in more than 75 countries and more than 71,000 patients have been treated in both the clinical trial and post-marketing settings with over 87,000 patient years of exposure.
Source: MarketWatch Copyright © 2013 MarketWatch, Inc (03/10/13)
Novartis International AG has announced that new data showing the benefits of Gilenya on patient outcomes in multiple sclerosis will be presented at the 29th Congress of the European Committee for Research and Treatment in Multiple Sclerosis in Copenhagen, Denmark.
Novartis said the new four-year data from the pivotal FREEDOMS and FREEDOMS extension studies plus a separate analysis of three studies (FREEDOMS, FREEDOMS II and TRANSFORMS) will show the benefits of continued Gilenya treatment on brain volume loss compared to delayed treatment of two years. The company said these data will reinforce the correlation between brain volume loss and disability, underlining the need for addressing brain volume loss in patients with Multiple Sclerosis.
Data from international and U.S. real-world databases will also confirm the favourable effect of Gilenya on reducing relapse rates for patients with Multiple Sclerosis, the company said.
Source: RTT News Copyright © 2013 RTTNews (25/09/13)
FDA warns of PML case with Gilenya(29/08/13)
A patient being treated for multiple sclerosis and who had no history of using natalizumab (Tysabri) developed progressive multifocal leukoencephalopathy (PML) while taking fingolimod (Gilenya), the FDA said.
"This is the first case of this disease ... reported following the administration of Gilenya to a patient who had not previously received Tysabri," the agency said in a statement posted on its website.
The patient, living somewhere in Europe, had been on fingolimod for "nearly 8 months" when PML was diagnosed, according to the FDA. The agency stopped short of saying fingolimod caused the condition, however.
"We are working with Gilenya's manufacturer, Novartis, to obtain and review all available information about this occurrence," the agency said. "We will communicate our final conclusions and recommendations after our evaluation is complete."
For its part, Novartis issued a statement indicating that the firm does not believe fingolimod was responsible for PML in this case, which it had reported publicly in late July.
"Having reviewed all available information, Novartis considers that several features of this case of PML make it unlikely to be attributable to Gilenya," the company asserted.
Fingolimod was not the only drug the patient had been taking, both Novartis and the FDA noted.
"The patient had been treated with interferon beta-1a and azathioprine for 1 month before initiating Gilenya treatment; those medications were stopped when Gilenya was started. The patient also received multiple courses of intravenous corticosteroids for several months before and during Gilenya treatment," according to the FDA.
Novartis said "MRI reviewers" had examined brain scans taken before the patient started on fingolimod and determined that the patient might already have had PML, because lesions seen in the scans were "atypical" in MS.
PML results from reactivation of latent infection with the JC virus, usually in patients with acute or chronic immunosuppression. The death rate has recently been about 20%.
It was first noted in patients receiving cancer chemotherapy and later in those infected with HIV. A series of PML cases seen with natalizumab after the drug was first approved in 2004 led to its temporary removal from the market.
In the current case, the patient showed JC virus DNA in cerebrospinal fluid as well as clinical symptoms, and fingolimod was stopped, the FDA said. The agency's statement indicated the patient is still alive.
The FDA advised clinicians to report side effects involving fingolimod to its adverse-event reporting system. It also told patients currently taking the drug not to stop it without talking first with their physicians.
Source: MedPage Today © 2013 MedPage Today, LLC.(29/08/13)
A patient taking Novartis' multiple sclerosis pill Gilenya developed a rare and potentially fatal viral disease, the Swiss drugmaker said on Tuesday, an unexpected setback as it faces growing competition from new oral treatments.
Gilenya is one of Novartis' big new drug hopes, growing 66 percent in the second quarter to $468 million. But the drug faces competition from new medicines such as Biogen Idec's Tecfidera.
Novartis said it had been informed of a case of progressive multifocal leukoencephalopathy (PML) in a patient who had been taking Gilenya for MS for seven months. It said it was working with the reporting physician to understand all possible contributing factors, including those beyond treatment, given several atypical features of the case.
"The course of the underlying neurological disease was rapid with some atypical findings for MS on the MRI scans of the brain and spinal cord, as well as some unusual clinical features," Novartis said in a statement.
Novartis said all previously reported cases of PML among the approximately 71,000 patients treated with Gilenya thus far had been attributed to prior treatment with Biogen Idec's Tysabri, which bears a known risk of PML.
Deutsche bank analyst Tim Race said the case may provoke some concerns about Gilenya's future growth potential. But he noted the incidence of reported PML cases for Gilenya has so far been extremely low.
"By the time there was a similar level of patient experience with Tysabri there had been 298 cases reported. Thus, even if the risk proves to be real it is likely to be of a very different order of magnitude," Race said in a note.
Source: Fox News.com ©2013 FOX News Network (30/07/13)
New data will be presented at the 23rd meeting of the European Neurological Society (ENS) that show how Novartis' Gilenya (fingolimod), the first once-daily oral therapy approved to treat people with relapsing multiple sclerosis (RMS), positively impacted the key measures for multiple sclerosis (MS) - relapse rates, brain volume loss, lesions and disability progression. Improving these key measures led to favorable clinical outcomes.
New findings from the TRANSFORMS study showed that a greater proportion of patients were disease free after one year on Gilenya treatment compared to interferon. For patients on interferon during the first year, the proportion who were disease free during the second year increased after they were switched from interferon to Gilenya treatment. These findings suggest that switching from interferon to Gilenya is beneficial for patients with RMS to achieve and maintain long-term disease-free status.
In a separate analysis, patients with high disease activity who were switched to Gilenya from interferon experienced improved disease measures (annualized relapse rate and reduction in the amount of brain volume loss), regardless of previous treatment.
Further presentations at ENS will show how the targeted effect of Gilenya on the central nervous system is considered to contribute anti-inflammatory effects in MS and also support a positive benefit-risk profile for Gilenya.
"There is currently no cure for MS, and therefore it is imperative that treatments work positively to limit symptoms, disease activity and ultimately disease progression, thus reducing the burden for patients." said Dr. Timothy Wright, Global Head Development, Novartis Pharmaceuticals. "These new analyses are very encouraging in that they not only support the role of Gilenya as having an anti-inflammatory effect but also highlight how Gilenya can improve the key measures of this debilitating disease."
Additional findings from FREEDOMS and TRANSFORMS support the clinical relevance of brain volume loss in MS, reinforcing the link between loss of brain volume and disease severity including the volume of brain lesions and disability, a key measure of disease burden. Gilenya is the only approved MS treatment shown to consistently reduce brain volume loss across studies with a significant effect seen as early as six months. A low rate of brain volume loss with Gilenya was sustained for up to four years in Phase III studies and for up to seven years in patients after completing a Phase II study.
Source: MarketWatch Copyright © 2013 MarketWatch, Inc (05/06/13)
People with relapsing multiple sclerosis (MS) reported greater treatment satisfaction after starting the oral treatment Gilenya® (fingolimod) vs. switching to, or staying on, injectable interferon beta or glatiramer acetate, according to new study data presented at the 2013 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) in Orlando, Fla.1
The US phase IV randomized, multi-center, open-label study, called EPOC (Evaluate Patient OutComes), evaluated treatment satisfaction among more than 1,000 patients.1,2 The study compared Gilenya to interferon beta or glatiramer acetate using a 100-point scale based on the Treatment Satisfaction Questionnaire for Medication (TSQM),1 a validated tool that measures patient satisfaction with medical treatments.3 A higher TSQM score indicates higher satisfaction.
At six months, adjusted mean treatment global satisfaction subscale scores (a measure of the overall level of satisfaction with a medication that patients are taking) were 80.4 for Gilenya vs. 61.1 for the injectable disease modifying therapies (DMTs), an increase from baseline by 20.4 vs. 2.9, respectively.1 The mean difference between the two scores was a statistically significant 17.5 (p<0.001).1
"Patient satisfaction is critical for the management of chronic conditions like MS," said Christopher LaGanke, MD, of North Central Neurology Associates in Cullman, Ala., and a study investigator. "These treatment satisfaction results are meaningful to clinicians and add important real-world insight to the established clinical trial evidence we already have for fingolimod."
A separate analysis of EPOC indicated that the overall incidence of infection was similar among patients taking Gilenya and patients taking standard injectable DMTs – consistent with results from previous studies.4 The analysis also found no observed relationship between lymphocyte counts and infection rates.4
"We led a revolution in MS treatment two years ago with the introduction of the first oral disease modifying therapy," said Dr. Timothy Wright, Global Head Development, Novartis Pharmaceuticals AG. "We are committed to continuing to provide critical insights to help physicians understand the role of Gilenya."
With more than two years on the market, Gilenya is approved in 72 countries and more than 63,000 patients worldwide have been treated with Gilenya.5 This includes both clinical trials and patients prescribed Gilenya.5
1. Fox E. et al. Treatment Satisfaction and Clinical Improvement After Switch to Fingolimod. Abstract Presented at CMSC, Orlando, May 2013.
2. U.S. National Institutes of Health (NIH), ClinicalTrials.gov; available at: http://clinicaltrials.gov/ct2/show/NCT01216072 : last accessed 5.02.13.
3. Atkinson M J. et al. Validation Of A General Measure Of Treatment Satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), Using A National Panel Study Of Chronic Disease. Health and Quality of Life Outcomes 2004;2:12.
4. LaGanke C. et al. No Effect on Incidence of Infection After Therapy Switch to Fingolimod. Abstract Presented at CMSC, Orlando, May 2013.
5. Data on file. Novartis Pharmaceuticals Corporation East Hanover, NJ.
Source: The Sacramento Bee Copyright © The Sacramento Bee 2013 (31/05/13)
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.
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)
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 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)
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)
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)
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.(25/09/12)
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)
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)