Plegridy™ (PEGylated interferon beta)
Biogen Idec received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the marketing authorisation of Plegridy™ (peginterferon beta-1a), a pegylated interferon administered subcutaneously for adults with relapsing-remitting multiple sclerosis (RRMS).
The CHMP’s positive opinion is now referred to the European Commission (EC), which grants marketing authorisation for medicines in the EU.
“The CHMP’s positive opinion for Plegridy marks an important milestone in bringing a meaningful treatment advance to people with MS in the EU,” said Douglas E. Williams, Ph.D., Biogen Idec’s executive vice president of Research and Development. “We believe Plegridy will offer physicians and those living with MS a unique treatment option that combines efficacy, a favourable safety profile consistent with the established interferon class, and a once-every-two-week dosing schedule.”
The CHMP opinion is primarily based on Phase 3 data from ADVANCE, one of the largest studies conducted with an interferon treatment in MS, which included more than 1,500 MS patients. Data from the first year of ADVANCE demonstrated that Plegridy, dosed once every two weeks, significantly reduced annualised relapse rate (ARR) at one year by 36 percent compared to placebo (p=0.0007). Plegridy reduced the risk of 12-week confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), by 38 percent (p=0.0383) compared to placebo. Plegridy also significantly reduced the number of new or newly enlarging T2-hyperintense lesions compared to placebo. The ADVANCE two-year data was consistent with the positive efficacy and safety results observed in year one.
“In Plegridy, we have a potential treatment that offers a less frequent dosing schedule, while providing robust clinical and MRI results,” said Professor Dr. Bernd C. Kieseier, Heinrich-Heine Universität. “These factors combined with the known safety profile of the interferon class, make it a compelling option for patients with RRMS.”
The safety and tolerability profile of Plegridy observed in ADVANCE was consistent with that of established MS interferon therapies. The most commonly reported adverse drug reactions (ADRs) with Plegridy treatment (incidence greater-than or equal to 10% and at least 2% more frequent on Plegridy than on placebo) were injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia.
Following the opinion adopted by the CHMP, a decision from the EC is expected within the coming months.
Plegridy is an investigational subcutaneous injectable therapy for relapsing-remitting multiple sclerosis (RRMS), in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body. Plegridy is a member of the interferon class of treatments for MS.
Clinical and MRI data from the ADVANCE study of Plegridy demonstrated a reduction in relapses, disability progression and the number of MS lesions when compared to placebo, and further support its clinical efficacy profile.
Source: MarketWatch Copyright © 2014 MarketWatch, Inc (27/05/14)
Tests of a new long-acting version of one of the oldest multiple sclerosis (MS) drugs on the market show it worked significantly better than placebo in reducing the number of patient relapses and developments of new or active lesions, researchers report. Most important, they add, the updated version was effective even though injections were given every two weeks instead of every other day, and it appears that fewer patients develop resistance to it.
The industry-funded, international clinical trial led by a Johns Hopkins scientist found that pegylated interferon beta worked far better than placebo for people with the most common form of MS. The beneficial effects seen in this study were comparable to what was found in previous studies in which the standard formulation of interferon beta (which must be taken more frequently) was compared to placebo.
In a report on the trial, published May 1 in The Lancet Neurology, the researchers say they also found that while roughly 20 percent of MS patients typically develop antibodies against the drug that ultimately neutralize its effects, fewer than 1 percent in the new study did, suggesting far more patients could benefit from the new formulation. "While this isn't a brand new blockbuster drug, I do think it will improve compliance and tolerability and therefore positively impact the quality of life of people with MS who take interferon beta," says study leader Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine. "If it gets FDA approval, this new formulation would allow patients to get the same effect, but instead of the burden of injecting themselves every other day, they only have to do it twice a month. For an MS patient, that's a huge advance."
"The data are very, very clear," Calabresi adds. "We can make things easier for our patients without dangerous side effects just by tweaking what we know to be a safe, 20-year-old drug."
MS is considered an autoimmune disorder, caused when the immune system wrongly attacks a person's own tissues; in this case, it's the fatty protein myelin sheath that insulates nerves that send electrical signals to control movement, speech and other functions. The immune system primes so-called T cells in the body's lymph nodes, preparing them to seek out and destroy myelin, a process that can lead to debilitating symptoms such as blurred vision, weakness and numbness.
In 1993, interferon beta became the first drug federally approved for MS because of its ability to block certain types of immune cell activation and the trafficking of immune cells into the brain. While some studies suggest its effects are modest in controlling MS, Calabresi says it works very well in some patients, overall reducing relapses by one-third and inflammation as measured using MRI by more than two-thirds.
Side effects trouble many patients—including flu-like symptoms that tend to occur in the six to eight hours after each injection—but Calabresi says the drug is safer for routine care than some newer oral medications.
Calabresi says his team was eager to test the new formulation, because many MS patients forego its benefits because of the frequent injection schedule and side effects. The new version modifies interferon beta by attaching polyethylene glycol (PEG) polymer chemical chains that stabilize the drug. PEG has been proven safe in other medications, shampoos, toothpaste and moisturisers.
For the study, researchers recruited more than 1,500 subjects with MS from 183 sites in 26 countries. For a year, one-third of patients got a placebo shot every two weeks, one-third got 125 micrograms of pegylated interferon beta shots every two weeks and the third group got 125 micrograms of pegylated interferon beta-1a once a month, with a placebo shot given at every other visit.
After a year, those who got pegylated interferon beta-1a every two weeks experienced a 36 percent reduction in the yearly relapse rate compared to the placebo group; the every-four-week group saw a 28 percent reduction. MRI scans revealed 67 percent fewer new or active lesions in the two-week group, while those injected every four weeks only had 28 percent fewer of those lesions.
Both the two- and four-week groups had 38 percent reduction in disability progression on a scale that measures walking speed, vision, strength and sensation, as compared to a placebo group.
The new formulation appeared just as safe as the older one, though Calabresi says that the flu-like symptoms from the long-acting drug lasted closer to 24 hours after each injection in some patients. He called this a trade-off his patients would deem worthwhile.
Data presented April 29 at the American Academy of Neurology suggests that receiving pegylated interferon beta every two weeks is the best dosing schedule.
Source: MedicalXpress © Medical Xpress 2011-2014 (01/05/14)
The US Food and Drug Administration has extended the initial Prescription Drug User Fee Act (PDUFA) date for its review of US biotech firm Biogen Idec’s Biologics License Application for Plegridy (peginterferon beta-1a), a subcutaneous pegylated interferon candidate for relapsing forms of multiple sclerosis (RMS).
The PDUFA date has been extended by three months, which is the standard extension period. The FDA has indicated that the extension of the PDUFA date is required to allow additional time for review of the application. The agency has not asked for additional studies, noted Biogen Idec.
Regulatory authorities in the USA and the European Union accepted the marketing applications for the review of Plegridy in RMS last year. Assuming that Plegridy comes to the market, it will add to Biogen Idec’s already strong MS franchise, which includes one of the leading drugs in the sector, Tysabri (natalizumab), as well as Avonex (interferon beta 1a) and more recently approved Tecfidera (BG-12, dimethyl fumarate), which many analysts have said could become the leading treatment for MS.
Source: The Pharma Letter © The Pharma Letter Limited 2014 (19/03/14)
Biogen Idec announced new data analyses from year one of the two-year, pivotal, Phase 3 ADVANCE study of PLEGRIDY(TM) (peginterferon beta-1a). PLEGRIDY is an investigational subcutaneous injectable for relapsing forms of multiple sclerosis (RMS), in which interferon beta-1a is pegylated to prolong the molecule's exposure in the body and enable the study of a less frequent dosing schedule. Clinical and MRI data from the study demonstrated a reduction in relapses, disability progression and the number of MS lesions when compared to placebo, and further support the clinical efficacy profile of PLEGRIDY. These data will be presented this week at the 29(th) Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark 2-5 October.
"If approved, PLEGRIDY could become a valuable addition to the interferon class of multiple sclerosis therapies," said Professor Peter Calabresi, MD, director, The Johns Hopkins Multiple Sclerosis Center. "The combination of efficacy demonstrated across key disease measures and a less frequent dosing schedule has the potential to offer an important therapeutic option for people living with MS."
Improvements Seen in Clinical and MRI Endpoints
Over one year, absence of measured disease activity (defined as no relapses, no disability progression, no gadolinium-enhancing [Gd+] lesions and no new or newly enlarging T2-hyperintense lesions compared to baseline) among patients, was significantly higher with PLEGRIDY: 34 percent in the two-week dosing arm (p<0.0001) and 22 percent in the four-week dosing arm (p=0.01), compared to 15 percent in the placebo arm.
In the intent-to-treat population of the ADVANCE study, PLEGRIDY, when dosed every two weeks, significantly reduced the number of new or newly enlarging T2-hyperintense lesions, new T1-hypointense lesions, new Gd+ lesions and new active lesions compared to placebo at 48 weeks. Specifically, PLEGRIDY reduced the number of:
-- New T1-hypointense lesions by 53 percent in the two-week dosing arm (p<0.0001) and 18 percent in the four-week dosing arm (p=0.082), ns
-- New active lesions by 67 percent in the two-week dosing arm (p<0.0001) and 35 percent in the four-week dosing arm (p<0.0001)
And, as previously reported at the American Academy of Neurology's 65(th) Annual Meeting in March 2013:
-- New or newly enlarging T2-hyperintense lesions by 67 percent in the two-week dosing arm (p<0.0001) and 28 percent in the four-week dosing arm (p=0.0008)
-- New Gd+ lesions by 86 percent in the two-week dosing (p<0.0001) and 36 percent in the four-week dosing arm (p=0.07), ns
"We believe the new analyses reinforce the efficacy of PLEGRIDY, which has been shown consistently across key MS disease measurements. They further support its potential as a treatment option for people living with this disease," said Gilmore O'Neill, vice president, Global Neurology Clinical Development at Biogen Idec. "The ADVANCE study results we have seen to date indicate that PLEGRIDY may have a positive effect on the reduction of relapses, disability progression and the reduction of lesion development."
Clinical and MRI results, including a post-hoc analysis evaluating the absence of measured disease activity from year one of the ADVANCE study, will be presented in the poster session titled, "Immunomodulation/Immunosuppression," on Thursday, 3 October at 3:45 p.m. -- 5:00 p.m. CET:
-- Peginterferon Beta-1a Provides Improvements in Clinical and Radiological
Disease Activity in Relapsing Multiple Sclerosis: Year 1 Findings from the Phase 3 ADVANCE Study (poster 514)
Additional MRI results from the first year of ADVANCE will be presented in the poster session titled, "II Immunomodulation/Immunosuppression," on Friday, 4 October at 3:30 p.m. -- 5:00 p.m. CET:
-- Magnetic Resonance Imaging Results from the First Year of the ADVANCE Study, a Pivotal Phase 3 Trial of Peginterferon Beta-1a in Patients with Relapsing-Remitting Multiple Sclerosis (poster 989)
PLEGRIDY is a new molecular entity in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body. PLEGRIDY is a member of the interferon class of treatments, which is often used as a first-line treatment for MS.
Regulatory authorities in the United States and the European Union accepted the marketing applications for the review of PLEGRIDY in RMS in July 2013.
The two-year Phase 3 ADVANCE clinical trial is a global, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of PLEGRIDY in 1,516 patients with relapsing-remitting MS. The study investigates two dose regimens of PLEGRIDY: 125 mcg administered subcutaneously every two weeks or every four weeks compared to placebo. The analysis for all primary and secondary efficacy endpoints occurred at one year.
In the ADVANCE clinical trial, PLEGRIDY met all primary and secondary endpoints by significantly reducing disease activity, including relapses and disability progression, compared to placebo, and showed favorable safety and tolerability profiles at one year. PLEGRIDY also reduced the number of new or newly enlarging T2-hyperintense lesions and the number of Gd+ lesions on brain MRI scans after one year.
After the first year, patients on placebo are re-randomized to one of the PLEGRIDY arms for the duration of the second year of the study. After completing two years in the ADVANCE study, patients have the option of enrolling in an open-label extension study called ATTAIN and will be followed for up to four years.
Source: The Wall Street Journal ©2013 Dow Jones & Company, Inc (01/10/13)
US and EU regulatory authorities accept Plegridy(TM) (peginterferon beta-1a) marketing applications for review(22/07/13)
Biogen Idec announced that U.S. and EU regulatory authorities have accepted the marketing applications for the review of Plegridy(TM) (peginterferon beta-1a), the company's pegylated subcutaneous injectable candidate for relapsing forms of multiple sclerosis (MS). The U.S. Food and Drug Administration (FDA) has accepted Biogen Idec's Biologics License Application (BLA) for marketing approval of PLEGRIDY in the United States and granted the company a standard review timeline. The Marketing Authorisation Application (MAA) of Plegridy for review in the European Union was also validated by the European Medicines Agency.
The regulatory applications included positive one-year results from the two-year global Phase 3 ADVANCE study. The data demonstrated that Plegridy met all primary and secondary endpoints by significantly reducing disease activity including relapses, disability progression and brain lesions compared to placebo, and showed favourable safety and tolerability profiles at one year.
"We expect that interferons will remain an important and widely used option for patients with MS. At one-year, Plegridy demonstrated significant reductions in relapses and disability progression, as well as a robust impact on several MRI endpoints," said Douglas E. Williams, Ph.D., Biogen Idec's executive vice president of Research and Development. "Plegridy, if approved, could offer a less frequent dosing schedule, a favorable safety profile, and the potential to become the preferred interferon treatment."
Plegridy is a new molecular entity in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body. Plegridy is a member of the interferon class of treatments, which is often used as a first-line treatment for MS.
Source: Market Watch Copyright © 2013 MarketWatch, Inc (22/07/13)