Positive Topline Phase 3 Results for Daclizumab HYP in MS

Susan Jeffrey

June 16, 2014

Topline results of a phase 3 trial show treatment with daclizumab high-yield process (HYP), an investigational once-a-month therapy, was superior to daily interferon β-1a (IFN β-1a) on the study's primary endpoint, with a statistically significant 45% reduction in annualized relapse rate (ARR).

Biogen Idec and AbbVie, the companies jointly developing daclizumab HYP, released topline results of the DECIDE trial today. Positive results of the first phase 3 trial of this agent, SELECT, and its extension trial, SELECTION, have already been reported.

The safety profile was consistent with that seen in previous studies, the companies note. "Biogen Idec and AbbVie plan to work with regulatory agencies to determine appropriate timelines for filing," they write. "The companies intend to present detailed results from DECIDE at a future medical conference."

Monoclonal Antibody

Daclizumab HYP is a new form of humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at high levels on T cells that become abnormally activated in MS. It modulates interleukin-2 signaling without causing general immune cell depletion. It is believed to work by decreasing abnormally activated T cells and proinflammatory lymphoid tissue inducer cells and increasing CD56bright natural killer cells that help regulate the immune system.

DECIDE was a 2- to 3-year, phase 3, global, double-blind, multicenter, active comparator study designed to determine whether treatment with the new drug would provide superior outcomes on clinical endpoints compared with IFN β-1a. The study enrolled more than 1800 people with relapsing-remitting MS in 28 countries. Patients were randomly assigned to receive 150 mg of subcutaneous daclizumab HYP every 4 weeks or IFN β-1a, 30 μg given by intramuscular injection once weekly.

The primary endpoint of DECIDE was the reduction in ARR. Secondary endpoints included the number of new or newly enlarging T2-hyperintense lesions, the proportion of patients with sustained disability progression on the Extended Disability Status Scale (EDSS), 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).

Results showed daclizumab HYP produced a statistically significant 45% reduction in ARR compared with IFN β-1a (P < .0001). 

It also showed superiority on the first secondary endpoint, number of new or newly enlarging T2-hyperintense lesions at week 96, with a 54% reduction relative to IFN β-1a (P < .0001). On the second secondary endpoint, treatment with daclizumab HYP reduced the risk for 3-month confirmed disability progression using the EDSS by 16% over IFN β-1a, but this difference didn't reach statistical significance (P = .16).

"Using a pre-specified sensitivity analysis that accounted for 67 patients who did not have a confirmatory disability assessment, daclizumab HYP showed a 21% reduction in the risk of sustained disability progression vs IFN β-1a (P = .047)," the release notes.

The overall incidence of adverse events was similar across the daclizumab HYP and IFN β-1a treatment groups, the companies said. In patients receiving daclizumab HYP compared with IFN β-1a, there was an increased incidence of serious infections (4% vs 2%), serious cutaneous reactions (2% vs <1%), and elevations of liver aminotransferase levels greater than 5 times the upper limit of normal (6% vs 3%).

Four patients in the IFN β-1a group and 1 in the daclizumab HYP group died; none of the deaths were considered treatment related, the companies note.

After completing the DECIDE study, patients have the option to participate in an open-label extension study called EXTEND.  

"The results of the DECIDE study are compelling, with (daclizumab) HYP demonstrating robust efficacy compared to a current standard of MS care," said Gilmore O'Neill, vice president, Global Neurology Clinical Development, Biogen Idec. "As a potential once-monthly therapy with a novel mechanism of action, we believe that, if approved, (daclizumab) HYP will be an important treatment option for people living with MS."

"The positive results in the DECIDE study represent achievement of an important milestone in the development of (daclizumab) HYP as a potential new treatment option for MS patients," said Michael Severino, MD, executive vice president, research and development and chief scientific officer at AbbVie. "Together, the companies are committed to working with regulatory agencies on filing plans," for the drug, he added.

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