− Post-Hoc Analyses Presented at ECTRIMS Demonstrate Effect on Disability and Cognitive Outcomes –
− Additional Analyses Reinforce Safety Profile of ZINBRYTA −
CAMBRIDGE, Mass. & NORTH CHICAGO, Ill.--(BUSINESS WIRE)--Full results from the Phase 3 DECIDE study published this week in the New England Journal of Medicine (NEJM), as well as new post-hoc analyses of Phase 3 clinical data presented at an international congress, show once-monthly, investigational ZINBRYTA™ (daclizumab high-yield process [HYP]) improved results on key measures of multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS (RRMS) compared to interferon beta-1a 30 mcg intramuscular (IM) injection. In the new post-hoc analyses, ZINBRYTA was shown to increase the percentage of patients achieving no evidence of clinical and MRI disease activity, improve cognitive processing speed and reduce 24-week confirmed disability progression across a broad range of subgroups at two years compared to interferon beta-1a IM. Lead investigators on behalf of Biogen (NASDAQ: BIIB) and AbbVie (NYSE: ABBV) presented these new findings today at the 31st Congress of the European Committee for Treatment and Research in MS (ECTRIMS) in Barcelona, Spain (7-10 October).
“The new DECIDE data presented at ECTRIMS provide further insight into the potential of daclizumab HYP to reduce MS disease activity, including the efficacy it has demonstrated in reducing MS relapse rates, disability progression and brain lesion development,” said Ludwig Kappos, M.D., chair, Department of Neurology and head, MS-Research Group, University Hospital, Basel, Switzerland, and lead investigator for DECIDE. “Over the two years of data we analyzed, nearly twice as many patients treated with daclizumab HYP had no evidence of MS disease activity compared to those taking an approved MS treatment.”
Efficacy Compared to Interferon Beta-1a IM
New post-hoc analyses of data from DECIDE presented at ECTRIMS assessed multiple measures of MS disease activity and showed that compared to interferon beta-1a IM over two years (p values are nominal):
“These new analyses advance our understanding of ZINBRYTA and its ability to slow the progression of MS compared to a widely used, approved therapy,” said Gilmore O’Neill, M.D., vice president of Multiple Sclerosis Research and Development at Biogen. “In addition, we are encouraged by the positive results of the analyses of ZINBRYTA on measures of cognitive function, which is also at risk as MS progresses.”
The full results from the pivotal Phase 3 DECIDE study were published in the 8 October 2015 issue of the NEJM. The DECIDE trial enrolled more than 1,800 patients with RRMS in 28 countries. The full manuscript, titled, “Daclizumab HYP Versus Interferon Beta-1a in Relapsing Multiple Sclerosis,” can be found on the NEJM website at http://www.nejm.org.
“There is still significant unmet medical need for patients with relapsing-remitting multiple sclerosis. We are encouraged by these results and the potential ZINBRYTA may have for people living with MS,” said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie.
Analysis of Safety Results
An integrated analysis of the safety and tolerability data from six clinical studies involving 2,236 RRMS patients treated with ZINBRYTA, including some patients treated for more than five years, was presented at ECTRIMS (888 patients were treated for ≥3 years, 211 patients were treated for ≥5 years). These results support the known benefit-risk profile of ZINBRYTA and indicate that adverse events (AEs) did not appear to increase over time.
Over a median of 30 months of exposure, the incidence of infections (59%), cutaneous events (33%), and hepatic events (16%) did not increase over time. The most common AEs (incidence ≥10%) associated with ZINBRYTA were MS relapse (31%), nasopharyngitis (20%), upper respiratory infection (15%), headache (13%) and urinary tract infection (10%).
A separate post-hoc analysis of cutaneous AEs occurring in the DECIDE study showed that cutaneous events were more common with ZINBRYTA treatment (37%) than with interferon beta-1a (19%). Most patients treated with ZINBRYTA who reported mild (81%) or moderate (73%) cutaneous events were not treated with a corticosteroid or were treated with topical corticosteroids. Serious cutaneous AEs (2%) were commonly managed in patients with systemic corticosteroids.
ZINBRYTA ECTRIMS Data Presentations:
DECIDE was a two- to three-year, Phase 3, global, randomized, double-blind, multicenter study designed to determine if ZINBRYTA would provide superior outcomes for certain clinical endpoints compared to treatment with interferon beta-1a 30 mcg IM injection. DECIDE was an active comparator study with two groups: 150 mg of subcutaneous ZINBRYTA every four weeks was compared to interferon beta-1a 30 mcg IM once weekly.
In DECIDE statistical significance was achieved on the primary endpoint of reduction in annualized relapse rate (ARR), as well as on the first secondary endpoint, the number of new or newly enlarging T2-hyperintense lesions. However, based on the primary prespecified analysis, statistical significance was not achieved on the secondary endpoint evaluating the proportion of patients with sustained disability progression as measured by the Expanded Disability Status Scale (EDSS) at 12 weeks. Additional secondary endpoints included the proportion of relapse-free patients and the proportion of patients who experienced a worsening physical impact score on the Multiple Sclerosis Impact Scale (MSIS-29).
The overall incidence of AEs was similar in the ZINBRYTA and interferon beta-1a IM groups. In patients treated with ZINBRYTA compared to interferon beta-1a IM, there was an increased incidence of serious infections (4% versus 2%), serious cutaneous reactions (2% versus <1%), and elevations of liver transaminases greater than five times the upper limit of normal (6% versus 3%).
About ZINBRYTA™ (daclizumab high-yield process)
ZINBRYTA (daclizumab high-yield process) is an investigational compound being developed for the treatment of relapsing forms of MS. ZINBRYTA is a new form of a humanized monoclonal antibody that selectively binds to the high-affinity interleukin-2 (IL-2) receptor subunit (CD25) that is expressed at high levels on T-cells that become abnormally activated in MS. ZINBRYTA modulates IL-2 signaling without causing general immune cell depletion. Biogen and AbbVie are jointly developing ZINBRYTA.
ZINBRYTA is believed to work by decreasing abnormally-activated T-cells and pro-inflammatory lymphoid tissue inducer cells, and increasing CD56bright natural killer (NK) cells, important cells that help regulate the immune system.
ZINBRYTA is currently under regulatory review in the United States, Australia and the European Union.
Through cutting-edge science and medicine, Biogen discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hematologic conditions and autoimmune disorders. Founded in 1978, Biogen is one of the world’s oldest independent biotechnology companies and patients worldwide benefit from its leading multiple sclerosis and innovative hemophilia therapies. For product labeling, press releases and additional information about the company, please visit http://www.biogen.com.
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