October 25, 2007 (Prague) — The monoclonal antibody daclizumab helps reduce the number of new or enlarged gadolinium-enhancing brain lesions in patients with active relapsing-remitting multiple sclerosis (RRMS) who are on interferon-beta, according to preliminary results of a phase 2 clinical trial.

 

The results were presented here at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS).

First Controlled Trial to Evaluate Daclizumab in MS

The CHOICE study is an ongoing phase 2 clinical trial evaluating the safety and efficacy of daclizumab vs placebo as add-on treatment to interferon-beta. It is the first randomized, placebo-controlled study assessing the effects of daclizumab in patients with MS.

The trial enrolled 230 patients with active MS in 51 centers throughout the United States and Europe. To be included, patients were required to have at least 1 gadolinium contrast–enhancing lesion on magnetic resonance imaging (MRI) or at least 1 relapse period in the previous 12 months and to have been on interferon-beta for at least 6 months.

The trial had 3 treatment groups: 2-mg/kg daclizumab subcutaneously every 2 weeks (high dose); 1-mg/kg daclizumab every 4 weeks (low dose); or placebo. The study drug was given for 24 weeks, and patients will be monitored for an additional 48 weeks. The primary end point of the study was the number of new or enlarged gadolinium-enhancing lesions between weeks 8 and 24, and the secondary end point was the relapse rate between weeks 8 and 24.

Significant Reduction in Lesions

The investigators found that study patients who received high-dose daclizumab showed a statistically significant 72% reduction (P = .004) in the number of new or enlarged gadolinium-enhancing lesions at week 24, compared with patients on interferon-beta therapy alone. The low-dose group showed a 25% reduction compared with the control group, but this difference between groups was not statistically significant.

"A positive effect was evident very early on — just 4 weeks after the initiation of the trial," said lead investigator Xavier Montalban, MD, head of the clinical neuroimmunology unit at the Hospital Val D'Hebron, in Barcelona, Spain. He also pointed out during his presentation that the dropout rate was very low, with 90% of patients completing the treatment.

With regard to safety, Dr. Montalban reported that there was a similar incidence of overall infections in all groups, but serious infections were more frequent in the daclizumab-treated groups. "Also, we saw a higher incidence of cutaneous events with daclizumab and a higher incidence of injection-site reactions," he added. However, there were no opportunistic infections or deaths in any of the groups, he noted.

In his concluding remarks, Dr. Montalban reiterated that daclizumab substantially reduced the number of new or enlarged gadolinium-enhancing lesions at the 2-mg/kg dose in patients who were already on interferon therapy.

"Larger studies are planned to determine efficacy and more clearly define safety and risk with regard to infections and cutaneous events," Dr. Montalban said. "We'll assess longer-term issues of safety and efficacy, and those data will be presented very soon," he added.

The CHOICE study is jointly sponsored by Biogen Idec and PDL BioPharma. Dr. Montalban acts as a consultant for both of these companies.

23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis: Parallel session 4 (50). Presented October 12, 2007.