Phase 2 Data Show Daclizumab Significantly Reduced Multiple Sclerosis
Lesions in Patients Receiving Interferon Beta Therapy
12 October 2007
Biogen Idec Inc. and PDL BioPharma, Inc. (PDL) announced today that Phase 2 data demonstrated a significant reduction in new or enlarged gadolinium-enhancing lesions when daclizumab is added to interferon beta therapy in patients with active relapsing multiple sclerosis (MS). These data will be presented tomorrow at the 23rd Congress of the European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic.
The ongoing Phase 2, randomized, double blind, placebo-controlled clinical study, known as the CHOICE trial, studies MS patients who continue to have active MS disease while receiving interferon beta therapy. The study patients who received daclizumab 2 mg/kg subcutaneously every two weeks showed a statistically significant 72% reduction in the number of new or enlarged gadolinium-enhancing lesions (Gd+) at week 24, compared to patients on interferon beta therapy alone. Patients from the CHOICE study were followed for an additional 48 weeks after the daclizumab treatment period to further assess safety and efficacy.
"Patients who received daclizumab every two weeks experienced far fewer new or enlarged gadolinium-enhancing lesions than the control group, which indicates that the antibody may be a promising option for patients with MS," said Dr. Xavier Montalban, Director of the Unit of Clinical Neuroimmunology at the Hospital Val D'Hebron in Barcelona, Spain. "In addition, we were encouraged to see a trend in the reduction of the number of relapses, or exacerbations, that these MS patients experienced. Further study is warranted."
Daclizumab is a humanized monoclonal antibody that targets the IL-2 receptor on activated T cells. Biogen Idec and PDL plan to initiate the SELECT study, a Phase 2 trial of daclizumab alone in the same relapsing patient population, by the end of 2007.
"We are very pleased to see positive results from the CHOICE study, the first randomized trial of daclizumab in patients with relapsing MS," said Mark A. McCamish, M.D., Ph.D., chief medical officer, PDL BioPharma. "We recognize how monoclonal antibodies have changed modern medicine and see great potential in their ability to treat serious diseases, including cancer and select immunological diseases such as MS. We're very excited to move development of daclizumab forward with our partner Biogen Idec, the acknowledged leader in the MS field."
"Daclizumab represents an exciting opportunity within our growing MS portfolio," said Alfred Sandrock, M.D., Ph.D., senior vice president, neurology research and development, Biogen Idec. "MS is a complex disease that requires an arsenal of treatment options for patients. We look forward to advancing the daclizumab development program and initiating the SELECT trial by the end of the year."
The CHOICE trial is evaluating the efficacy and safety of daclizumab or placebo added to interferon beta therapy in 230 patients with active MS who were enrolled at study centers in the U.S. and Europe. Patients were randomized to receive daclizumab 2 mg/kg every two weeks, daclizumab 1 mg/kg every four weeks, or placebo added to ongoing interferon beta treatment.
The primary efficacy analysis showed that at 24 weeks, the 75 patients in the 2 mg/kg group experienced 72% fewer new or enlarged Gd+ on average compared to the 77 patients who received a placebo (p=0.004). The 78 patients in the 1 mg/kg group experienced a 25% reduction in new or enlarged lesions compared with placebo but that measurement did not achieve statistical significance.
Based on data up to week 24, analysis of the relapse rate, which was a secondary endpoint, indicates that both daclizumab regimens revealed a trend in reducing the annualized relapse rate compared to placebo (an approximately 35% reduction), but these observations did not reach statistical significance.
Preliminary safety data showed similar rates of infection across all treatment groups with an overall greater incidence of serious infections in the daclizumab treated groups. (4.6% versus 1.3% placebo). Urinary tract infections were slightly higher with the 2 mg/kg dose (17% vs 13% placebo). The incidence of cutaneous events was higher in the combined daclizumab groups (34% daclizumab vs. 27% placebo) but was mild to moderate and most resolved with little or no treatment.
PDL and Biogen Idec entered into a collaboration agreement in 2005 to co- develop and commercialize daclizumab in MS and indications other than transplant and respiratory diseases. Under the collaboration, the companies are also co-developing volociximab (also known as M200), an antibody in Phase 2 development for the treatment of various solid tumors. PDL and Biogen Idec share equally the costs of all development activities and all operating profits for both products within the U.S. and Europe. The companies jointly oversee development, manufacturing and commercialization plans for collaboration products and divide implementation responsibilities to leverage each company's capabilities and expertise. Each party will have co-promotion rights in the U.S. and Europe. Outside the U.S. and Europe, Biogen Idec will fund all incremental development and commercialization costs and pay a royalty to PDL on sales of collaboration products.
Source: Biogen Idec Inc. and PDL BioPharma, Inc. (12/10/07)
Treatment: CCSVI both IJV ballooned 09/2010, No DMDs, Tysabri on hold after 24 Infusions, after LDN, ABX Wheldon Regime for 1 year.