Daclizumab trial for relapsing-remitting MS begins
ZenapaxActive Comparator Study Designed to Examine the Safety and Efficacy of Daclizumab Formulated for Monthly Subcutaneous Dosing.
Biogen Idec and Abbott today announced enrollment of the first patient in a global Phase III study evaluating the efficacy and safety of daclizumab compared to interferon beta-1a (Avonex(R)) in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS).
The trial, called DECIDE, will investigate a subcutaneous formulation of daclizumab intended for monthly administration, which has the potential to provide a new immunomodulatory approach for treating MS. Under the terms of the collaboration agreement, Biogen Idec will make a $30 million milestone payment to Abbott. This payment is due upon enrollment of the first patient in the DECIDE trial.
"Despite significant advances in MS therapy, many patients continue to experience disease activity. The MS community is eager for new treatment approaches," said Ludwig Kappos, M.D., Head, MS-Research Group, University Hospital, Basel, Switzerland, and lead investigator for the study. "As shown in previous studies, daclizumab appears to selectively target immune cells that are thought to become activated in MS and cause damage to the central nervous system."
DECIDE is a global Phase III, randomized, double-blind, active-comparator study expected to enroll approximately 1,500 RRMS patients in 28 countries. The trial will investigate a subcutaneous formulation of daclizumab intended for once-monthly administration as a monotherapy compared to treatment with interferon beta 1-a, one of the most common treatments for MS. Daclizumab is also being investigated in the ongoing Phase IIb registration-enabling SELECT trial, which is evaluating the efficacy and safety of monthly subcutaneous doses of either 150 mg or 300 mg of daclizumab monotherapy.
"The DECIDE study builds on the positive results we saw in the CHOICE trial, which showed that daclizumab, when added to interferon beta, significantly reduced MS lesions compared to interferon beta therapy alone," said Alfred Sandrock, M.D., Ph.D., Senior Vice President of Neurology Research and Development at Biogen Idec. "Initiating this trial demonstrates our commitment to developing new treatment options for patients who suffer from this terrible disease."
"Initiating the Phase III DECIDE trial is a tremendous milestone for the collaboration as it brings daclizumab one step closer to becoming a potential new treatment option for patients with MS," said Eugene Sun, M.D., Vice President, Global Pharmaceutical Clinical Development, Abbott. "Extensive preclinical and clinical experience with daclizumab suggest this drug holds promise as a new approach for the treatment of MS, and we look forward to expanding our knowledge further with the DECIDE trial."
Multiple sclerosis, one of the most common neurological disorders, affects more than 2.5 million people worldwide. In MS, certain immune cells, called T-cells, become activated and are believed to migrate to the central nervous system (CNS), releasing cytokines that injure nerve fibers in the CNS and cause the symptoms of MS.
Daclizumab is a humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at low levels on resting T-cells and at high levels on T-cells that are thought to become activated in response to MS. Daclizumab is believed to work by selectively targeting these activated T-cells without causing general T-cell depletion.
Data from the Phase II CHOICE trial demonstrated that daclizumab 2mg/kg administered subcutaneously every two weeks in combination with interferon beta (IFNB) therapy led to a 72 percent reduction in the number of new or enlarged MS lesions when compared to IFNB therapy alone in patients with active, relapsing forms of MS. Additional analysis from the study revealed that daclizumab led to an increase of a subset of natural killer cells (CD56bright NK cells) that help regulate the immune system. This increase was associated with a significant reduction in MS lesion formation. The incidence of common adverse events was similar in all treatment groups. Some serious adverse events occurred in daclizumab treated patients, which were most commonly infections that resolved with standard interventions.
DECIDE (Daclizumab HYP Efficacy Compared to Interferon Beta 1-a Study for Multiple Sclerosis) is a two- to three-year, Phase III, muliticenter, double-blind, randomized, parallel-group, monotherapy, active-control study designed to determine the efficacy and safety of daclizumab versus interferon beta 1-a, one of the most common MS treatments, in patients with RRMS. The trial is expected to enroll approximately 1,500 RRMS patients in 28 countries. The study will include patients between the ages of 18 to 55 years with an Expanded Disability Status Scale (EDSS) score ranging from 0.0 to 5.0.
The primary objective of the study is to determine the efficacy of daclizumab compared to interferon beta 1-a in preventing MS relapse, with annualized relapse rate as the primary endpoint. The study will also examine the efficacy of daclizumab compared to interferon beta 1-a in slowing functional decline and disability progression and in maintaining quality of life.
During the 96- to 144-week treatment period, all study participants will receive either a subcutaneous injection of daclizumab 150 mg once every four weeks or weekly injections of interferon beta 1-a.
Daclizumab is a humanized monoclonal antibody that binds to the CD25 alpha subunit of the high affinity IL-2 receptor. CD25 is expressed at low levels on resting T-cells (immune cells) 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 binding to and inhibiting this receptor on activated T-cells without causing T-cell depletion. Daclizumab is an investigational agent in clinical development for the treatment of MS under a collaboration between Facet Biotech, acquired by Abbott in April 2010, and Biogen Idec. Daclizumab is currently being studied in two registrational clinical trials in patients with MS.
Source: Biogen Idec (24/05/10)
Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.