European Medicines Agency determines that dimethyl fumarate in MS drug Tecfidera qualifies as a new active substance(22/11/13)
Biogen Idec Inc. said the European Medicines Agency's Committee for Medicinal Products for Human Use determined that dimethyl fumarate in its drug Tecfidera qualifies as a new active substance.
Shares jumped 10% to $276.97 in early trading, as the designation provides 10 years of regulatory exclusivity in the European Union for the multiple-sclerosis treatment. The stock is up about 90% so far this year.
The determination follows a positive opinion by the committee in March recommending marketing authorization in the EU for the drug as a first-line treatment for adults with relapsing-remitting multiple sclerosis.
The CHMP's determination will be referred to the European Commission, which grants marketing authorization for medicines in the EU. If approved, Tecfidera will mark the fourth therapy for MS that Biogen offers in the EU.
Biogen is aiming to become the dominant maker of MS treatments, a group of drugs that command high prices and that patients typically take for years.
The U.S. Food and Drug Administration in March approved Tecfidera, one of a new class of oral pills predicted to eventually become the standard of care for MS, replacing the injectable therapies that now comprise the bulk of the market. According to IMS, Tecfidera is the leading oral MS therapy in the U.S.
Biogen has been bolstering its sales force and readying its manufacturing supply chain as some drugs in its late-stage product pipeline move closer to entering the market.
Its third-quarter earnings rose 22% on stronger sales from Tecfidera.
Source: 4-traders Copyright © 2013 Surperformance (22/11/13)
Latest results from the clinical trial program with BG-12 (dimethyl fumarate; Tecfidera, Biogen Idec) suggest sustained clinical efficacy and safety in patients with multiple sclerosis (MS) taking the drug for up to 4 years.
In addition, a separate post hoc analysis of the phase 3 pivotal Determination of the Efficacy and Safety of Oral Fumarate in Relapsing–Remitting MS (DEFINE) and Comparator and an Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (CONFIRM) clinical trials shows that BG-12 reduced relapses and disease activity in treatment-naive patients.
The latest long-term results come from the ENDORSE study, an extension phase of the DEFINE and CONFIRM trials.
Commenting on these results for Medscape Medical News, Bernd Kieseier, MD, Heinrich Heine University, Düsseldorf, Germany, who did a talk rounding up meeting highlights including these new results, said, "These are reassuringly meaningful clinical results showing that the effects of BG-12 over 2 years are maintained in the third and fourth year, with no additional safety concerns."
Ralf Gold, MD, St. Josef-Hospital/Ruhr-University in Bochum, Germany, a leading investigator in the extension study, said, "When making MS treatment decisions, we weigh efficacy and safety considerations, so it is encouraging to see that the positive profile of BG-12 observed in the DEFINE and CONFIRM studies has been maintained in the ENDORSE clinical trial to date."
These data were presented at the recent 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Newest Oral Therapy
BG-12 is one of the new oral therapies for multiple sclerosis. It was approved by the US Food and Drug Administration in the United States and is going through the reimbursement process in Australia and Canada.
In Europe, regulatory authorities are still reviewing the drug, with "data exclusivity" discussions ongoing. Biogen told Medscape Medical News that it has strong patent protection for the product, but the company is in discussions with the European authorities on regulatory data protection "to ensure maximum coverage is in place."
Of the 2651 patients who participated in DEFINE and CONFIRM, 1736 were enrolled in ENDORSE. Patients who received BG-12 in the DEFINE or CONFIRM studies continued receiving the drug at the same dosage — twice daily (BID) or 3 times daily (TID) — in ENDORSE. Patients who received placebo in DEFINE or glatiramer acetate (GA) in CONFIRM were randomly assigned to BG-12 BID or TID.
Interim efficacy results at 2 years into ENDORSE suggest efficacy and safety of BG-12 similar to those shown in the DEFINE and CONFIRM studies.
Professor Kieseier commented to Medscape Medical News: "The obvious question at the end of a 2-year clinical trial is: 'Will these results be maintained over time?' We can see from these latest results that the benefit has been maintained, and in the patients switched from placebo or glatiramer acetate the annual relapse rate has come down to a similar level as those who were taking BG-12 long-term."
He added: "Of course, it would be nice to have a comparison with placebo long term but this can't be done, so the closest we can get is to follow patients to see if a low level of disease activity continues and that seems to be the case. We are seeing a similar relapse rate in the third and fourth years as we did in the first and second year of BG-12 treatment. That is encouraging."
Professor Kieseier noted that annual relapse rates of 0.1 to 0.2, as seen in ENDORSE, are typical of what is achieved with other long-term effective drug therapies. "We don't have a drug that gets this down to zero," he said.
In terms of safety, no new adverse effects were reported in patients continuing to receive BG-12 in ENDORSE. The most common adverse events in patients who were switched to BG-12 from placebo or GA were flushing and gastrointestinal events, the incidences of which were generally similar to those observed in DEFINE and CONFIRM, Biogen reports. The most common adverse event in patients continuing to receive long-term BG-12 is nasopharyngitis (common cold).
Similar to what was seen in CONFIRM and DEFINE, mean lymphocyte counts in patients who switched to BG-12 in ENDORSE decreased over the first year of treatment and then plateaued. The incidence of lymphocyte counts 0.5 × 109/L was 6% to 8% in the continued BG-12 groups and 5% to 9% in the new-to-BG-12 groups.
For patients who continued treatment with BG-12, mean lymphocyte counts were generally stable and mean counts remained within normal limits at all time points, the researchers note. They add that there was no overall increased risk for serious infections or malignancies in patients continuing to receive, or new to, BG-12 treatment. And there was no overall increased risk for renal dysfunction or hepatic adverse events in any treatment group.
Asked about the lymphocyte count reduction, Professor Kieseier said, "It is something that needs to be considered, but I don't think it is a major concern. The other drugs also show this effect. But it seems to happen relatively infrequently with BG-12."
He added that BG-12 did not seem to have severe toxicities. "Patients will appreciate that. The driving interest in this drug at the moment is its good efficacy paired with good tolerability, and these results show that this profile continues to be there in the long-term."
MRI results from ENDORSE showed continued that treatment with BG-12 resulted in a low frequency of new/enlarging T2 hyperintense lesions, new nonenhancing T1 hypointense lesions, and gadolinium-positive lesions over 4 years. Patients initially randomly assigned to placebo or GA who then received BG-12 in ENDORSE demonstrated MRI outcomes similar to those observed with BG-12 treatment in the parent studies.
In a separate post hoc analysis from the phase 3 DEFINE and CONFIRM studies of 678 new treatment-naive patients with MS, BG-12 was associated with a 50% reduction in relapse rate compared with placebo. Patients taking BG-12 also had a significantly reduced risk for disability progression and a significant positive effect on MRI outcomes in this patient population.
Several researchers involved in these studies are employees of Biogen Idec. Dr. Gold receives honoraria and/or research support from Bayer, Biogen Idec, Merck Serono, Novartis, and Teva. Professor Kieseier has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, sanofi-aventis, and TEVA.
29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Poster #538, #990, #996, and #1004.
Source: Medscape Multispecialty Copyright © 1994-2013 by WebMD LLC (18/10/13)
Biogen Idec Inc. said its new multiple-sclerosis drug, Tecfidera, wasn't to blame for the death earlier this year of a 59-year-old woman who had taken the pill.
In July, the Weston, Mass., biotech company said it was investigating the death of the woman from a form of pneumonia that the company said was common in multiple-sclerosis patients. She had taken Tecfidera for 5½ weeks before vomiting, diarrhea and other side effects prompted her to stop taking the pill, and died 2½ weeks after discontinuing treatment, the company had said. The woman had a history of irritable bowel disease and recurring infections like bronchitis, according to the company.
A Biogen spokeswoman said Monday that the physician who treated the woman concluded that Tecfidera wasn't the cause and that the company agreed with the assessment. "The case has been assessed and it was determined that the death was unrelated to Tecfidera," the spokeswoman said. Biogen has declined to identify the woman.
Tecfidera was approved in March to treat patients suffering from periodic attacks of multiple sclerosis, a painful neurological condition in which the immune system damages healthy nerves and disrupts brain signals.
Early sales for the pill have been strong, and some analysts expect it could eventually notch more than $4 billion in yearly world-wide revenue. In the second quarter of this year, Tecfidera generated $192 million of Biogen Idec's $1.4 billion revenues.
The drug is up for approval in the European Union.
During testing, the most common side effects were flushing, as well as nausea, vomiting and diarrhea, especially at the start of treatment, according to the U.S. Food and Drug Administration. Another risk, the agency said, was a decrease in the count of white blood cells that help fight off infections, though there wasn't a significant increase in infections among study subjects taking Tecfidera.
Last week, Biogen presented data at a medical meeting in Copenhagen showing "no new or worsening safety signals," such as a higher risk of serious infections, in study subjects who had been taking the drug for up to 6½ years.
Source: The Wall Street Journal Copyright ©2013 Dow Jones & Company, Inc (08/10/13)
The death of a patient who had taken Biogen Idec Inc's new multiple sclerosis drug, Tecfidera, was unlikely to be linked to the medicine, the company said on Monday.
Biogen said it was made aware last week of the death of a 59-year-old woman who had been treated with Tecfidera, and that it was actively gathering facts about the case.
Based on the circumstances of the case and the cause of death, "a link to Tecfidera is unlikely," said Biogen spokeswoman Kate Niazi-Sai.
"The patient was not on Tecfidera at the time of death," she added.
Tecfidera, which is widely expected to become the No. 1 oral treatment for the disease, with annual sales of more than $3 billion, was launched in April. Biogen is expected to report sales for the drug's first few weeks on the market on Thursday.
The patient had taken Tecfidera for a little over five weeks, but discontinued using the drug due to gastrointestinal (GI) problems, such as vomiting and diarrhoea, Biogen said.
She had been off the drug for more than two weeks prior to her death, which was reported as caused by a type of pneumonia more common to MS patients and not due to GI events, the company added.
The death was first reported by BioPharm Insight, and it briefly sent the company's shares down more than 3 percent before they rebounded. They closed up 0.6 percent at $231.67 on Nasdaq.
"I see this as a non-issue," Mark Schoenebaum, an analyst at ISI Group, told clients in an email.
Source: Reuters © Thomson Reuters 2013 (23/07/13)
BioTrends Research Group finds that, despite being the third oral disease-modifying therapy (DMT) to launch in the U.S. multiple sclerosis (MS) market, 53 percent of surveyed U.S. neurologists have prescribed Biogen Idec's Tecfidera to at least one of their MS patients after only one month on the market. This rate for Tecfidera surpasses that for Novartis's Gilenya (19 percent), the first-to-market oral DMT, and Genzyme's Aubagio (16 percent), the second-to-market oral DMT, at the same stage of product launch.
Data from the recently published LaunchTrends: Tecfidera Wave 1 report suggest that this impressive physician trial rate is likely to continue to grow over the coming months, with nearly all surveyed neurologists anticipating at least some Tecfidera prescribing among their DMT-treated relapsing-remitting MS (RRMS) patients over the next six months. Coupled with this expansion in prescriber base, Tecfidera patient share among DMT-treated RRMS patients is anticipated to increase significantly from 2 percent to 15 percent, beating that projected for Aubagio (4 percent) and Gilenya (6 percent) by November 2013.
Given the previous dominance of injectable DMTs in the MS market, it is not surprising that neurologists identify Tecfidera's oral formulation as being one of its main advantages, similar to the attitudes observed with the launches of Aubagio and Gilenya. However, the report finds that early Tecfidera trial and uptake may be driven more by neurologists' comfort with Tecfidera's safety profile and positive efficacy perceptions--together with the low monitoring burden required with Tecfidera treatment, especially compared to other oral DMTs--than by its mode of administration.
Nonetheless, the report also reveals that the upward trend in Tecfidera prescribing may be hampered by managed care issues, with neurologists recalling that up to one-quarter of Tecfidera prescriptions required proof of failure on a previous DMT despite Tecfidera's label not including any line restrictions. During qualitative interviews, a subset of Tecfidera prescribers expressed frustration in the time taken for patients to receive Tecfidera, with neurologists suggesting that delays may be due, in part, to preauthorization requirements with managed care companies.
"Given neurologists' hesitancy to switch patients who are responding well to their current DMT, potential managed care issues, and anticipated stable treatment rates, the projected increase in Tecfidera trial and adoption may end up being somewhat more muted," said BioTrends Research Group Analyst Emma Williams, Ph.D. "However, even if neurologists' conservative prescribing patterns blunt some of the trajectory, uptake will most likely still drive Tecfidera into a market leading position among oral DMTs by the end of 2013."
Source: Market Watch Copyright © 2013 MarketWatch, Inc (11/07/13)
No question, Biogen Idec's new multiple sclerosis pill charged out of the gate. Tecfidera is selling so well that it's expected to break the blockbuster barrier by next year. But the launch has hit a few bumps, The Wall Street Journal reports, putting CEO George Scangos under pressure to smooth Tecfidera's path.
In a way, Tecfidera has been a victim of its own success. Patients and doctors had been eagerly awaiting its debut, and there just wasn't enough of the drug to go around. Pent-up demand "overwhelmed" some pharmacies, Scangos told the WSJ. It didn't help that supply chain and manufacturing snags interfered with distribution.
Meanwhile, some insurers have been slow to approve reimbursement for Tecfidera, doctors say. Some patients have waited several weeks for the go-ahead. Some payers want proof that patients have failed on other drugs before they'll foot the bill for Tecfidera. "I'm surprised with the amount of stuff I'm dealing with in this launch, compared to other ones," the University of Pennsylvania Multiple Sclerosis Center's director, Clyde Markowitz, told the Journal. To ease the way, Biogen has offered Tecfidera for free to patients who have to wait longer than two weeks for reimbursement.
One problem could be the drug's price. It's $54,900 a year. That's slightly less than its only other oral competitor, Novartis' Gilenya, but more than older injectable treatments, such as Biogen's own Avonex. And gaining reimbursement nods for expensive drugs, even convenient oral treatments, could be even tougher as generics hit the market. Scangos himself figures that price increases in MS are "probably not sustainable," the WSJ says.
Some obstacles facing Tecfidera--including a launch delay in austerity-minded Europe--aren't unique. Drugmakers are rolling out pricier therapies these days, at a time when payers are increasingly vigilant about controlling their drug costs. Reimbursement hurdles are common. No wonder drugmakers are thinking about reimbursement earlier and earlier, before regulatory approval is imminent.
Source: FiercePharma © 2013 FierceMarkets (20/06/13)
A post hoc analysis of phase 3 studies in patients with relapsing-remitting multiple sclerosis (RRMS) clearly showed that those taking the oral agent BG-12 (dimethyl fumarate; Tecfidera, Biogen Idec Inc.) experienced significant improvements in physical and mental functioning, general well-being, and overall health status, whereas those receiving placebo typically reported declines in these measures of quality of life.
"After treatment with BG 12, both the 3-times-a-day and twice-a-day dosing, at the first measurement point at 6 months, we're seeing either an improvement in quality of life or at least no change, whereas the placebo group is showing a consistent decrease in quality of life over this same period of time," said Mariko Kita, MD, Virginia Mason Medical Center, Seattle, Washington, who presented the research.
The results, using data from the pivotal DEFINE and CONFIRM trials, were presented here at the 5th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Measures of Well-being
Approved by the US Food and Drug Administration as a first-line oral treatment for MS earlier this year, BG12 has been used for decades as a treatment for psoriasis. It likely acts as an immunomodulating agent, inhibiting proinflammatory cytokines and chemokines and promoting anti-inflammatory activity. It also acts as an antioxidant and may also have a neuroprotective effect.
The current analysis included patients receiving placebo (n = 733), BG-12 twice daily (n = 741), and BG-12 3 times a day (n = 728). Patients completed the Short Form 36 health survey (SF-36) at 6, 12, and 24 months. Their global impression of well-being was assessed every 3 months using a visual analogue scale. Patients also completed the European Quality of Life–5 Dimensions health survey at 6, 12, and 24 months.
Patients taking BG-12 reported significant increases in mean physical component summary (PCS) and mental component summary (MCS) scores on the SF-36 at 2 years, whereas those receiving placebo had a decrease in these mean scores.
The proportion of patients who achieved a clinically relevant 5-point improvement in PCS and MCS scores was significantly higher for those taking BT-12. For example, for PCS, the odds ratio (OR) of BG-12 3 times a day compared with placebo was 1.48 (95% confidence interval [CI], 1.21 - 1.81; P = .0001). For MCS, the OR for that same group vs placebo was 1.63 (95% CI, 1.33 - 2.00; P < .0001).
Patients receiving the drug also did better in terms of well-being. The mean change on the Global Impression of Well-being (VAS) score in the placebo group was -4.0 compared with -0.3 and 0.1 in the BG-12 twice-daily and 3-times-daily groups, respectively (both P < .0001)
The physical, mental, and emotional measurements captured things such as depression, fatigue, cognitive problems, how well patients thought their pain was being controlled, and how disabled they felt.
Such information might influence choice of drugs and even reassure patients who are fearful of side effects, said Dr. Kita. "You would be surprised at the number of patients out there who opt to avoid treatment, and this is an important reminder that being on these treatments can have more benefit than meets the eye."
That is not to say that this drug is without side effects. When patients start taking this drug, they may experience nausea, diarrhea, vomiting, or flushing, said Dr. Kita. There can also be issues with a drop in lymphocyte count or even some liver dysfunction.
The DEFINE and CONFIRM trials had demonstrated an acceptable safety profile as well as significant clinical and magnetic resonance imaging efficacy in RRMS patients.
The DEFINE and CONFIRM trials were funded by Biogen Idec Inc. Dr. Kita reports that she has received research support from Biogen Idec Inc.
5th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Poster SX18. Presented May 30, 2013.
Source: Medscape News Today Copyright © 1994-2013 by WebMD LLC (03/06/13)
A new oral treatment for those living with multiple sclerosis has been approved for use in Canada.
Tecfidera is an oral medication recently approved by Health Canada.
It becomes just the second oral drug available in the country to treat multiple sclerosis – other treatments are done by injections.
Julie Kelndorfer has spent nine years living with MS and says it’s been a rollercoaster ride.
“It’s been an interesting journey for all of us, my whole family,” Kelndorfer.
Multiple sclerosis attacks the protective covering or myelin, of the brain and spinal cord, interrupting the flow of nerve pulses which affects vision, hearing, memory, balance and mobility.
Kelndorfer has a form of MS called relapsing-remitting.
She recently experienced an episode she’d never been through before.
“It was actually the MS attacking my brain stem so my balance was off, it was like I was having seizures, I was in a convulsion,” she said. “It was scary.”
After that episode, Kelndorfer stopped taking the daily injection medication she had been on for years.
She has since spent months researching Tecfidera to see if it will work for her.
“When something is new and exciting, at the same time you’re hesitant to be the first one out of the gate,” she said.
Kelndorfer is holding out hope that Tecfidera will mean fewer muscle spasms.
“I think it’s another arsenal in the fight against MS and I think that’s exciting,” she said.
High prevalence of MS in Alberta
Neurologist Dr. Fabrizio Giuliani says the prevalence of multiple sclerosis cases in Canada is high and those numbers are highest in Alberta.
“Alberta seems to have the highest prevalence. Some people talk of MS as the ‘Disease of Alberta’ because of the numbers,” Giuliani said.
The only other oral MS drug available in Canada comes with serious side effects that make it an option many doctors tend to avoid recommending.
That fact makes Tecfidera an attractive alternative treatment for patients.
“Every drug has side effects. We don’t have to forget that. It’s the severity of the side effects sometimes that can be different based on the mechanism of the drug,” he said. “For the Tecfidera it looks like the safety profile is quite good.”
According to the MS Society of Canada, clinical trials on hundreds of patients have shown Tecfidera reduces relapses by 53 per cent and slows the disease progression by 38 per cent.
Kelndorfer knows all therapies come with risks. She has read that Tecfidera is known to cause gastrointestinal problems but she’s willing to give the pill a try if it will – for the most part – improve her overall quality of life.
“The side effects seem fairly reasonable,” Kelndorfer said. “For the time that I’m living, I want a quality of life that let’s me be the mom, the wife, the employee.”
Kelndorfer says she was told by her doctor that she could be on the new treatment as early as next month.
These therapies cost anywhere between $20,000 to $40,000 a year.
Tecfidera still needs to undergo review by the Canadian Drug Expert Committee as well as a local expert committee before determining if the medication will be funded by the province.
“Both expert committees review new medications to ensure they are safe, efficient and cost-effective, ensuring Albertans are kept safe and that public dollars are spent with the best health outcomes in mind,” Alberta Health spokesperson John Muir said in a statement to CTV News.
Source: CTV News © 2013 Bell Media (08/05/13)
The active ingredient in a drug that’s expected to become a popular treatment for multiple sclerosis has been linked to four European cases of a rare but sometimes fatal brain disease called progressive multifocal leukoencephalopathy (PML).
The ingredient, dimethyl fumarate, is used in a drug called Fumaderm that was approved in Germany in 1994 to treat the skin condition psoriasis. It is also in a different but closely related medication called Tecfidera, which was just approved by the U.S. Food and Drug Administration in March for the treatment of multiple sclerosis (MS). It is known as a fumaric acid ester, which is commonly used as a food additive and has been used to treat psoriasis in Germany for 30 years.
According to reports published in the April 25 issue of the New England Journal of Medicine, however, four patients who were taking Fumaderm to treat their psoriasis developed PML.
In a letter responding to the reports, Biogen, the company that makes both drugs, said Tecfidera may be safer because it contains only dimethyl fumarate, while Fumaderm also contains three other fumaric acid esters.
The company also noted that none of the patients taking Tecfidera during clinical trials (then known as BG-12) developed PML. Since Tecfidera is a pill rather than an injection, and was effective and well-tolerated by patients in clinical trials, analysts have predicted it would soon become the top-selling multiple sclerosis treatment.
But the German doctor who treated one of the psoriasis patients who got PML thinks there is still cause for concern.
Dr. Jorg Schulz, a neurologist at Rheinisch-Westfaelische Technische Hochschule Aachen, a research university in Aachen, said the two drugs are virtually identical once they are broken down in the body.
“The problem is that the studies with BG-12 covered a two-year period, but no longer periods,” Schulz said, and he believes it may take prolonged treatment with the drug for PML to surface.
“With the publication of our case, we wish to create awareness that treatment with any form of fumaric acid may bear the risk of developing PML,” Schulz said.
PML is caused by the JC virus, which normally lies dormant in the body and causes no harm. About half of multiple sclerosis patients have antibodies to the JC virus in their blood, suggesting a current or former infection. When the immune system is depleted by illnesses like cancer or AIDS or suppressed by certain medications, the virus can flare and destroy nerve cells in the brain.
Ironically, PML is a lot like multiple sclerosis, but it progresses more rapidly as it causes weakness, paralysis, confusion, memory loss and loss of vision or speech. Quick treatment can stop the damage, although patients may be permanently disabled.
PML is rare, but it is so serious that Genentech pulled its psoriasis treatment Raptiva off the market in 2009 after reports of four cases in patients who were taking the biologic medication. Biologic drugs are medications derived from living organisms that are used to prevent certain diseases, including ones where the immune system malfunctions.
Another biologic, Tysabri, a treatment for multiple sclerosis and Crohn’s disease, was shelved in 2005 for about a year after three patients involved in clinical trials of the drug developed PML. Tysabri returned to the market in 2006 with strict new safeguards in place. Before starting the drug, for example, patients must get an MRI of their brains. They also may get blood tests to check for antibodies to the JC virus. They also are monitored by doctors every three to six months while taking the medication, which is also made by Biogen.
No such precautions are currently recommended for Tecfidera, which has been hailed as a less toxic alternative to other treatments. Other multiple sclerosis drugs are known to cause flu-like symptoms, chest pain, and heart, liver and eye problems.
In clinical trials, the main side effects reported with Tecfidera were comparatively mild, and included facial flushing, stomach upset and low white blood cell counts.
“The main reason why our [psoriasis] patient developed PML after three years of treatment with Fumaderm is prolonged lymphocytopenia [low white blood cell counts],” Schulz said. “In both BG-12 trials published in the New England Journal of Medicine in 2012, 4 percent to 5 percent of patients developed this kind of severe lymphocytopenia and are in my view at risk to also develop PML.”
Another expert noted another caveat.
About 3 percent of patients in the Tecfidera trials were taken off the medication when their white blood cell counts dropped too low, said Dr. Robert Fox, a staff neurologist at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio.
“The intensive monitoring of the clinical trial may have been what helped to prevent PML,” said Fox, who was on the steering committee for one of the studies that tested the medication and who has been a paid consultant for Biogen.
Fox added that the PML case reports are “very important additions to our understanding of this class of therapy.”
“Although we haven’t seen any PML cases in patients treated with Tecfidera, I think there’s good reason to apply the lessons learned here to Tecfidera,” he said.
Source: Health Copyright © 2013 Health Media Ventures, Inc (25/04/13)
The highly anticipated number is in: Biogen Idec's newly approved Tecfidera has a wholesale price of $54,900 per year, the biotech giant revealed on Friday. With the U.S. market debut of the oral multiple sclerosis drug set for Monday, Biogen plans to hit the market for MS pills with a lower price than Novartis' Gilenya, which is arguably the company's top competition.
The Tecfidera price falls on the high end of the $50,000 to $55,000 range predicted by RBC Capital Markets analyst Michael Yee. Existing MS pills on the U.S. market include Gilenya at $58,000 per year and Sanofi's Aubagio for $45,000, according to the analyst's numbers. So Biogen has set a middle-of-the-field price for a pill that many analysts expect to become the top therapy in the oral MS class.
"We think this price represents a solid value to the MS community and demonstrates our commitment to ensuring patient access," Biogen spokeswoman Monique da Silva told FiercePharma in an email.
Biogen has been a leading player in the MS market for years with top-selling injected therapy Avonex and the IV drug Tysabri, yet the company's sales organization needs to master a whole new pitch for Tecfidera with many physicians who are unfamiliar with the product. Naturally, docs will want to know how the MS pill stacks up with rival therapies. On the safety score, Tecfidera comes with a relatively clear profile compared with Aubagio, which is saddled with a black-box warning about increased risk of liver problems, and Gilenya, which regulators warn should not be used in patients with heart disease.
However, Gilenya has reduced relapse rates in MS patients in studies by about 54% compared with 44% to 53% in those studied on Biogen's pill and 30% in patients taking Aubagio in clinical trials, The New York Times reported. Yet analysts expect Tecfidera to ultimately garner the most sales. EvaluatePharma pegs the consensus estimate on peak sales of Tecfidera at $3.8 billion, more than most analysts expect Gilenya and Aubagio to bring in for their pharma providers.
Source: FiercePharma © 2013 FierceMarkets (02/04/13)
The Food and Drug Administration said Wednesday it approved a new drug from Biogen Idec to control multiple sclerosis in adults with hard-to-treat forms of the disease. The twice-a-day capsules, called Tecfidera, offer a new option for multiple sclerosis, a debilitating disease in which the body attacks its own nervous system. Cambridge, Mass.-based Biogen Idec already sells two other drugs for the disease, but both require injections.
There is no cure for multiple sclerosis and most patients experience relapses of symptoms, including loss of balance, weakness in arms and legs, and blurred vision. Over time patients usually become weaker and less coordinated. More than 2.5 million people worldwide have the disease, with about 400,000 of them in the U.S., according to Biogen. The FDA said it approved Tecfidera based on two studies showing patients taking the drug had fewer relapses than patients taking a dummy pill.
The approval gives Biogen a new product in an increasingly crowded field of multiple sclerosis drugs.
The biotech drugmaker already sells the once-a-week multiple sclerosis injection Avonex. It also markets the once-a-month injection Tysabri through a partnership with Elan Corp. PLC of Ireland. However, Tysabri's severe side effects have curtailed its use.
Tecfidera is designed to be taken orally, which could make it a preferred option for patients and doctors.
A Biogen executive said Wednesday that its three drugs would be used to treat different groups of patients.
"Multiple sclerosis is a reasonably complex disease and we think there are a lot of needs out there," said Tony Kingsely, a vice president at Biogen. "By having three drugs out there I think we can address a lot of those needs."
Kinglsey said the company will announce the pricing of the drug when it begins shipping in the next week.
Novartis launched the first pill-based multiple sclerosis drug, Gilenya, in March 2011. Sanofi won FDA approval for a second pill, its drug Aubagio, last September.
The top-selling drug for the disease worldwide is Copaxone, which is made by Teva Pharmaceutical Industries. That injection had sales of nearly $4 billion last year, according to Teva's latest financial report.
Avonex and Tysabri had annual sales of $2.7 billion and $1.5 billion in 2011, the most recent year for which Biogen has reported annual sales.
Source: Yahoo! News Copyright © 2013 Yahoo! Inc (28/03/13)
The Committee for Medicinal Products for Human Use (CHMP) issued positive opinions on two new MS therapies. Recommending the granting of a marketing authorisation for the medicinal product Tecfidera 120 mg and 240 mg, gastro-resistant hard capsules, intended for the treatment of adult patients with relapsing remitting multiple sclerosis and Aubagio 14 mg film-coated tablet intended for the treatment of multiple sclerosis.
The Committee also concluded that the active substance contained in Aubagio, teriflunomide, could not be considered to be a new active substance. It is expected that Sanofi-aventis will appeal against this conclusion.
The full Summaries Of Opinion can be read here: Tecfidera , Aubagio
Source: The Committee for Medicinal Products for Human Use (CHMP) (22/03/13)
Biogen Idec Inc announces it has been granted a new patent that will help protect the market exclusivity of its multiple sclerosis drug Tecfidera (BG-12) until 2028.
The new patent covers the dosing regimen for Tecfidera of 480 milligrams a day.
Tecfidera is expected to be approved by the U.S. Food and Drug Administration by the end of March and many analysts expect it to become the leading treatment for multiple sclerosis.
The European Patent Office also determined recently that a patent covering the same dosing regimen for Tecfidera is allowable. Once granted it too would expire in 2028.
Source: Reuters © Thomson Reuters 2013 (20/03/13)
FDA extends review of oral MS drug BG-12(18/10/12)
Biotechnology company Biogen Idec Inc said U.S. health regulators extended by three months the review date of its much-awaited multiple sclerosis (MS) drug BG-12, but analysts said the delay was only a minor setback.
Shares of Biogen were down 2 percent at $150.72 in morning trading on the Nasdaq.
The stock has risen more than 50 percent over the past 12 months, largely on optimism about BG-12, which showed robust results in trials and had no safety concerns.
Analysts said the delay would push the review date to March, but added such extensions were not uncommon.
"The registrational studies for BG-12 - DEFINE and CONFIRM - enrolled about 1,200 and 1,400 patients, respectively. Given the size and complexity of the filings, we are not surprised that the FDA would require additional time to review the application," Barclays Capital analyst Anthony Butler said.
The U.S. Food and Drug Administration said it needed additional time to review the application, but did not ask for additional studies, according to Biogen.
Butler and Wells Fargo Securities analyst Brian Abrahams pointed out that Sanofi's oral MS drug Aubagio also had its review extended earlier this year, but was later approved.
BG-12, also known as dimethyl fumarate, would be the second oral MS drug on the market, competing with Novartis AG's Gilenya.
Analysts expect sales of $390 million and $980 million for BG-12 in 2013 and 2014, Barclays's Butler said in a note.
The oral drug is currently also under regulatory review in the European Union, Australia, Canada and Switzerland.
Biogen also markets Avonex and Tysabri to treat relapsing-remitting MS, the most common kind of MS.
Multiple sclerosis affects 400,000 Americans and 2.5 million people worldwide, according to the National Multiple Sclerosis Society.
Source: Reuters © Thomson Reuters 2012 (18/10/12)
Biogen Idec Inc. said new data from studies evaluating its experimental multiple-sclerosis pill BG-12 further supports its effectiveness and safety in people with relapsing-remitting multiple sclerosis.
Most treatments for the chronic, inflammatory and potentially disabling disease are delivered by needle, but BG-12, or dimethyl fumarate, is an oral drug that will likely be taken twice daily. The drug is currently under review with U.S. and European regulators and could be approved early next year.
Biogen said Friday pooled data from the Phase 3 Define and Confirm studies showed statistically significant and clinically relevant reductions of multiple sclerosis relapses and progression of disability. The studies also found reductions in magnetic resonance imaging measures of disease activity.
In addition, interim safety data from a Phase 3 extension study indicated continued exposure to BG-12 didn't result in any new or worsening safety signals and were consistent with previous studies.
"These data provide additional insight into the positive efficacy and safety results from our Phase 3 studies, showing there is a consistent beneficial effect with dimethyl fumarate in reducing MS relapses, brain lesions and disability," said Alfred Sandrock, senior vice president of development sciences and chief medical officer. "If approved, dimethyl fumarate may provide a broad range of MS patients with an effective therapy that offers the ease of oral administration and an acceptable tolerability profile."
Biogen first released results from the Confirm study in October. The study met its main treatment goal by showing a reduced annualized relapse rate--which took into account the total number of relapses among all patients--for BG-12 patients compared with those on placebo. The study measured patients for two years and also included patients treated with Teva Pharmaceutical Industries Ltd.'s injectable MS drug Copaxone.
The company said in April its Confirm study of about 1,400 MS patients showed the most common side effects for BG-12 patients at two years were flushing, or reddening of the skin, and gastrointestinal issues such as diarrhea and nausea. These problems were more common with BG-12 than they were with a placebo, but the side effects decreased for BG-12 patients after the first month of treatment, Biogen said.
The positive data and high expectations for the MS treatment have helped to drive Biogen stock to around all-time high levels recently.
Source: MarketWatch Copyright © 2012 MarketWatch, Inc (12/10/12)
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.(28/09/12)
A new oral medication to treat patients in the early stages of multiple sclerosis has shown considerable promise in two clinical trials, researchers announced.
The medication is on track to become just the third oral drug available to M.S. patients, and potentially the safest and most effective, experts said. The second oral drug, called Aubagio, was approved just last week.
M.S. was virtually untreatable only two decades ago, but today nine “disease modifying” drugs are available for early-stage patients; a half-dozen more are in the late stages of development. Most patients in the early stage of the disease, a form called relapsing-remitting M.S., take drugs by injection.
The two new studies, published online in The New England Journal of Medicine, found that the drug BG-12, developed by Biogen Idec, reduced relapse rates in patients with relapsing M.S. by about 50 percent. The drug also significantly reduced the frequency of new brain lesions often associated with these attacks, and slowed the progression of disease compared with a placebo.
The studies were Phase 3 trials, a last step on the road to drug approval. The Food and Drug Administration is required to make a decision about the drug’s approval before the end of this year.
“This drug is clearly quite effective in managing disease and reducing disability, and the safety profile looks quite good,” said Timothy Coetzee, the chief research officer at the National Multiple Sclerosis Society, who was not involved in the studies.
Multiple sclerosis is often a progressive disease in which the immune system damages neurons in the brain and spinal cord. A majority of people with M.S. have relapsing-remitting M.S., characterized by flare-ups that cause lesions in the brain to develop and neurological symptoms to emerge or worsen. Eventually, more than half of patients develop a progressive form of M.S., leading to permanent disabilities.
Interferons, the drugs most commonly used in relapsing M.S., reduce relapses by about 30 percent, and have not been shown to slow the progression of the disease and disability. The newly approved Aubagio also reduces relapses by about 30 percent, and it has the advantage of being an oral drug.
Two drugs that are substantially more effective, Tysabri and Gilenya, come with serious risks including, in rare cases, death. They are used as second-line treatments when an initial approach fails, and patients require some monitoring.
In the new studies, called Define and Confirm, patients were randomized into two groups, taking 240 milligrams of BG-12 either twice or three times a day. Patients in a third group took a placebo. The combined results showed that the drug reduced the relapse rate by about 50 percent. There was minimal difference between the twice-daily and thrice-daily regimens.
Taking BG-12 twice a day reduced the number of new or newly enlarging brain lesions by 71 percent to 99 percent, depending on the type of lesion and the study. The Define study found a statistically significant 38 percent reduction in the progression to disability.
The most frequent side effects were a temporary flushing and warm feeling and gastrointestinal symptoms including nausea, diarrhea, cramping and vomiting. Though both types of side effects were common, they tended to diminish after the first few weeks of use and were tolerated by most patients.
BG-12 is an anti-inflammatory that works by protecting nerves against injury. It is a fumaric acid, very similar to one widely used in Germany for the treatment of psoriasis. “The safety track record is well known and appears to be very strong,” said Dr. Robert Fox, lead author of one of the two new studies and medical director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.
“It’s a bright day for M.S. patients, but there is a gray cloud in that we still don’t have anything for those with progressive M.S.,” he added.
Source: The New York times © 2012 The New York Times Company (20/09/12)
Both U.S. and European regulators have accepted for review Biogen Idec's application for experimental multiple sclerosis drug BG-12, the company said on Wednesday.
The pill is seen by some Wall Street analysis as having the potential to become the world's leading treatment for the chronic, disabling disease that attacks the central nervous system and can lead to numbness, paralysis and loss of vision.
Biogen already makes multiple sclerosis drugs Avonex and Tysabri, which are given by injection and infusion.
The company said the U.S. Food and Drug Administration granted a standard 10-month review for BG-12 and the European regulatory agency has validated its application. Both applications were submitted in the first quarter of this year.
Source: Reuters © 2012 Thomson Reuters (09/05/12)
The latest data on Biogen Idec Inc.'s (BIIB) experimental multiple-sclerosis pill BG-12 show "favorable safety and tolerability" that support the drug's use as a front-line treatment for MS patients, the biotechnology company said.
Details from the "Confirm" study on BG-12 were set for presentation at an American Academy of Neurology conference Tuesday. The drug is currently under review with U.S. and European regulators and could be approved early next year.
Positive data and high expectations for the MS treatment have helped drive Biogen shares to around all-time high levels recently. Most treatments for the chronic, inflammatory and potentially disabling disease are delivered by needle, but BG-12 is an oral drug that will likely be taken twice daily.
The Biogen-funded Confirm study of about 1,400 MS patients showed the most common side effects for BG-12 patients at two years were flushing, or reddening of the skin, and gastrointestinal issues such as diarrhoea and nausea. These problems were more common with BG-12 than they were with a placebo, but the side effects "decreased substantially" for BG-12 patients after the first month of treatment, the company said.
Meantime, BG-12 had a lower rate than placebo when it came to serious adverse events, which were mainly relapses of MS attacks. Also, the incidence of serious infections "was low and balanced across the study groups," and there were no malignancies among BG-12 patients, Biogen said.
The overall incidence of adverse events for patients on placebo was 92%. The rate was 94% for patients on two daily BG-12 doses and 92% for patients on three daily doses. The rate of serious events was 22% for placebo, 17% for two daily BG-12 treatments and 16% for three daily treatments.
"The safety profile has continued to hold up nicely from one study to the next," said Doug Williams, Biogen's executive vice president of research and development, in an interview.
Williams also said that Biogen believes BG-12 "should be front-line therapy for patients" based on the risk-benefit profile seen in BG-12 studies.
Biogen first released results from the Confirm study in October. The study met its main treatment goal by showing a reduced annualised relapse rate--which takes into account the total number of relapses among all patients--for BG-12 patients compared with those on placebo. The study measured patients for two years and also included patients treated with Teva Pharmaceutical Industries Ltd.'s injectable MS drug Copaxone.
Biogen hasn't disclosed how much BG-12 is expected to cost, but has said the price will likely be comparable to other MS agents. Patients in the Confirm study had the relapse, remitting form of MS, which involves flare-ups rather than constant disease progression. This is the most common form of the disease.
Source: Fox Business News ©2012 FOX News Network, LLC (24/04/12)
Biogen Idec Inc., a Weston-based biotechnology company known for its multiple sclerosis drugs, said it has submitted a New Drug Application to federal regulators to get approval to market a potential new MS treatment known as BG-12.
In December, Biogen Idec shares hit their high for 2011 after the company released promising results from a clinical trial of BG-12.
BG-12, the company’s designation for dimethyl fumarate, would be taken twice a day in pill form, and it is designed to treat of relapsing-remitting multiple sclerosis, sometimes called RRMS, the most common form of MS, Biogen Idec said in a press release.
Two other Biogen Idec MS drugs are delivered differently. Tysabri is administered in a once-a-month infusion, and Avonex is injected once a week, the company said.
Biogen Idec, which said today that it had submitted a New Drug Application to the US Food and Drug Administration, added that it plans to submit a similar request to European regulators within the next few days.
Biogen Idec said it anticipates hearing from regulatory authorities regarding the status and acceptance of its BG-12 submissions “within the next couple of months.”
In a separate press release this morning, the company said the FDA has approved two separate dosing innovations designed to improve the treatment experience for patients receiving Avonex. Currently, Avonex is delivered by syringe. What the FDA has approved is an “auto-injector” device for delivering a dose of Avonex. Because the auto-injector’s needle is thinner and shorter than that of a syringe, the hope is that the auto-injector will make things easier for patients.
Source: boston.com © 2012 NY Times Co (28/02/12)