Cambridge, Mass. and Redwood City, Calif. February 16, 2010 Biogen Idec (NASDAQ: BIIB) and Facet Biotech Corporation (NASDAQ: FACT) today announced the publication of Phase 2 data showing that the addition of daclizumab to interferon beta (IFNβ) led to a significant reduction in the number of new or enlarged multiple sclerosis (MS) lesions when compared to IFNβ alone in patients with active relapsing forms of MS. The trial, called CHOICE, also showed that daclizumab led to an increase in a subset of the natural killer (NK) cells that help regulate the immune system. These data were published in Online First, the online edition of The Lancet Neurology, and will be published in the April issue of the Lancet Neurology.
Study results showed that daclizumab 2mg/kg administered subcutaneously every two weeks in combination with IFNβ reduced the number of new or enlarged gadolinium contrast-enhancing lesions (Gd-CELs) by 72 percent versus IFNβ therapy alone. The presence of Gd-CELs is thought to indicate inflammation within the central nervous system that corresponds with MS disease activity. In addition, treatment with daclizumab resulted in a seven- to eight-fold increase of CD56bright NK cells, which was associated with a decrease in disease activity. Daclizumab was well-tolerated in the CHOICE trial and common adverse events occurred with a similar frequency in each of the treatment groups.
"The CHOICE trial demonstrated that daclizumab was associated with a robust increase in important cells that help regulate the immune system, as well as a significant reduction in MS lesion formation," said John W. Rose, M.D., professor of Neurology, Research Laboratory, Veterans Affairs Salt Lake City Health Care System and the University of Utah, and an author on the manuscript. "Previous studies have shown that people with MS have less of these immunoregulatory cells than people without MS which, coupled with the reduction in active lesions, supports further study of daclizumab."
Multiple sclerosis, one of the most common neurological disorders, affects more than 400,000 people in the United States each year. Despite significant advances in MS therapy, many patients continue to experience disease activity. There is a need for additional MS therapies that offer new approaches to treating the disease.
Daclizumab is a humanized monoclonal antibody that binds to CD25, a high affinity receptor that is expressed at low levels on resting T cells, which are a type of immune cell, and at high levels on T cells that can become activated in response to autoimmune conditions such as MS.
"Daclizumab is believed to work by selectively targeting immune cells that play a key role in MS without depleting healthy immune cells and has the potential to provide a new approach to treating this chronic and debilitating disease," said Gilmore O'Neill, senior director, Experimental Neurology at Biogen Idec. "Daclizumab was well tolerated in the CHOICE trial and significantly reduced MS activity in patients who were not responding to interferon beta."
"We believe the results from the CHOICE study, combined with clinical data from smaller trials of daclizumab in MS, provide a basis for advancing daclizumab into registrational studies as a novel therapeutic for the treatment of patients with relapsing MS," said Mark Rolfe, Ph.D., senior vice president and chief scientific officer of Facet Biotech. "Despite advances in MS treatment, there remains a significant unmet medical need for new therapies such as daclizumab and we look forward to seeing data from our registrational studies."
Results from this Phase 2 study provided evidence for Biogen Idec and Facet Biotech to continue the development of daclizumab in two registrational trials in MS. The Phase 2b SELECT trial is evaluating the efficacy and safety of monthly subcutaneous daclizumab as a monotherapy versus placebo, and is currently enrolling patients. The Phase 3 DECIDE trial is expected to be initiated in the second quarter of 2010.
The CHOICE study is the first randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of daclizumab (DAC) when added to IFNβ therapy. The study enrolled 230 patients, ages 18 to 55 years, with active relapsing MS who had an entry score of five or less on the Expanded Disability Status Scale (EDSS). The patients had to be taking a stable IFNβ regimen for a minimum of six months prior to enrollment. During the year prior to enrollment, patients had to have experienced at least one MS relapse or incurred at least one MS lesion of the brain or spinal cord while on a stable IFNβ regimen.
Patients remained on their baseline IFNβ regimens and were randomized in a ratio of 1:1:1 to three "add-on" treatment groups for 24 weeks: 2mg/kg daclizumab administered subcutaneously every two weeks (DAC high dose/ IFNβ); 1mg/kg daclizumab administered every four weeks (DAC low dose/ IFNβ); or placebo (placebo/ IFNβ).
The primary endpoint of the study was the total number of new or enlarged Gd-CELs measured monthly on brain MRI scans collected between weeks eight to 24. Additional endpoints included changes in the number and volume of lesions on TI- and T2-weighted MRIs, clinical relapse as assessed by the annualized relapse rate (ARR) and time to relapse, changes in EDSS and Multiple Sclerosis Functional Composite-3 (MSFC-3) scores, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), clinical laboratory abnormalities and adverse events (AEs).
Compared with patients on placebo/IFNβ therapy alone, there was a 72 percent reduction in the number of new or enlarged Gd-CELs between weeks eight and 24 in the DAC high dose/IFNβ group (p=0.004, 95% CI 34%, 88%) and a 25 percent reduction in the DAC low dose/IFNβ group (p=0.51, 95% CI -76%, 68%). Daclizumab reduced MS lesion activity as early as week four with an average of 2.1 new or enlarged MS lesions appearing in the placebo/IFNβ group versus 0.9 new or enlarged MS lesions for the DAC high dose/IFNβ group.
Daclizumab treatment was generally well-tolerated. Common adverse events were similar in all treatment arms. Grade 3 adverse events were observed in 24 percent of DAC/IFNβ-treated patients and 14 percent of placebo/IFNβ-treated patients. The most frequent grade 3 adverse events were infections, which occurred in 7 percent of DAC/IFNβ-treated patients and 3 percent of placebo/IFNβ-treated patients. There were no opportunistic infections or deaths, and all infections resolved with standard therapies.
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