Daclizumab Shows Promise in Multiple Sclerosis Trial

AMSTERDAM – Daclizumab reduced the rate of relapse and the rate of disability progression in patients with relapsing-remitting multiple sclerosis in a 1-year, placebo-controlled phase II trial .

The novel immunomodulatory therapy also reduced the number of new brain lesions detected on MRI while producing a very low rate of treatment discontinuation and a low rate of injection site reactions, [which is] consistent with a very good tolerability profile," study investigator Dr. Gavin Giovannoni said at the joint triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

Daclizumab (Zenapax) is a humanized monoclonal antibody targeted against the CD25 alpha subunit of the interleukin-2 receptor. It is currently approved for the prophylaxis of acute organ rejection in patients receiving renal transplants. Although it is not clear how daclizumab works, it is thought that the drug reduces the number of activated T cells and increases natural killer cell proliferation (J. Immunol. 2010;185:1311-20).

In the multicenter, double-blind SELECT study, 600 patients were randomized to receive subcutaneous injections of one of two doses of daclizumab (150 mg or 300 mg) or placebo every 4 weeks for up to 1 year.

Patients were eligible for the study if they had a diagnosis of relapsing-remitting multiple sclerosis confirmed with McDonald 2005 criteria and at least one relapse in the past 12 months with brain MRI consistent with MS or gadolinium-enhanced (GdE) lesion activity in the 6 weeks prior to randomization.

In an MRI substudy, 309 patients underwent monthly brain scans while the remaining study population underwent MRI at four time points: before treatment, 24 weeks after randomization, 26 weeks after randomization, and then 52 weeks after randomization. At baseline, the two groups of patients had a median age of 35-37 years and a median time since diagnosis of 2-3 years. About three-quarters of patients were treatment naive and had experienced 1.3-1.4 relapses in the past year. However, 52% of patients randomized to 150 mg daclizumab had one or more GdE lesions – a higher rate than that seen in either the 300-mg daclizumab or placebo groups (36% and 44%), reported Dr. Giovannoni of Queen Mary University in London.

At 1 year, the annualized relapse rate was 0.46 for placebo, 0.21 for daclizumab 150 mg, and 0.23 for daclizumab 300 mg. This represented reductions of 54% and 50%, respectively, in the rates of relapse, which were significant in comparison with placebo.

The percentage of patients who remained relapse free was 81% for daclizumab 150 mg and 80 % for daclizumab 300 mg; both rates were significantly better than for placebo (64%).

The percentage of patients with 3-month confirmed disability progression was 5.9% for the 150-mg dose, 7.8% for the 300-mg dose, and 13.3% for placebo. This was a "surprising result considering this was only a 52-week study [of] the impact of daclizumab on disability progression," Dr. Giovannoni said.

He and his coinvestigators also observed quality of life improvements with daclizumab treatment on physical scores on the Multiple Sclerosis Impact Scale–29, compared with placebo.

Results of the MRI substudy showed a significant 69%-78% reduction in new or enlarging GdE lesions between weeks 8 and 24 of the study in patients treated with daclizumab versus placebo, and a 79%-86% reduction in new or enlarging GdE lesions by the end of the 1-year study.

Adverse events occurred more often among patients in the daclizumab groups (72%-76% vs. 28% with placebo), but any serious event was more likely to occur in patients randomized to placebo (27% vs. 16%-18% for daclizumab).

One death potentially related to treatment occurred in the daclizumab arm. This was due to a complication of a psoas abscess occurring in a patient recovering from a serious cutaneous adverse event.

"The results of this trial have informed the ongoing [clinical trials] program, and monitoring and treatment algorithms have been put in place to mitigate any safety concerns," Dr. Giovannoni said.

Another two clinical studies of daclizumab are currently ongoing – an open-label, multicenter extension of the SELECT study and the phase III DECIDE trial. This latter trial is comparing up to 144 weeks of treatment with daclizumab against interferon beta-1a (Avonex) in about 1,500 patients with relapsing-remitting multiple sclerosis. Primary data from the trial are unlikely to be available until late 2013.

The SELECT study was supported by Biogen Idec and Abbot Biotherapeutics. Dr. Giovannoni disclosed receiving research support and/or consulting fees from Bayer Healthcare, Biogen Idec, and other manufacturers of MS therapies.

AMSTERDAM – Daclizumab reduced the rate of relapse and the rate of disability progression in patients with relapsing-remitting multiple sclerosis in a 1-year, placebo-controlled phase II trial .

The novel immunomodulatory therapy also reduced the number of new brain lesions detected on MRI while producing a very low rate of treatment discontinuation and a low rate of injection site reactions, [which is] consistent with a very good tolerability profile," study investigator Dr. Gavin Giovannoni said at the joint triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

Daclizumab (Zenapax) is a humanized monoclonal antibody targeted against the CD25 alpha subunit of the interleukin-2 receptor. It is currently approved for the prophylaxis of acute organ rejection in patients receiving renal transplants. Although it is not clear how daclizumab works, it is thought that the drug reduces the number of activated T cells and increases natural killer cell proliferation (J. Immunol. 2010;185:1311-20).

In the multicenter, double-blind SELECT study, 600 patients were randomized to receive subcutaneous injections of one of two doses of daclizumab (150 mg or 300 mg) or placebo every 4 weeks for up to 1 year.

Patients were eligible for the study if they had a diagnosis of relapsing-remitting multiple sclerosis confirmed with McDonald 2005 criteria and at least one relapse in the past 12 months with brain MRI consistent with MS or gadolinium-enhanced (GdE) lesion activity in the 6 weeks prior to randomization.

In an MRI substudy, 309 patients underwent monthly brain scans while the remaining study population underwent MRI at four time points: before treatment, 24 weeks after randomization, 26 weeks after randomization, and then 52 weeks after randomization. At baseline, the two groups of patients had a median age of 35-37 years and a median time since diagnosis of 2-3 years. About three-quarters of patients were treatment naive and had experienced 1.3-1.4 relapses in the past year. However, 52% of patients randomized to 150 mg daclizumab had one or more GdE lesions – a higher rate than that seen in either the 300-mg daclizumab or placebo groups (36% and 44%), reported Dr. Giovannoni of Queen Mary University in London.

At 1 year, the annualized relapse rate was 0.46 for placebo, 0.21 for daclizumab 150 mg, and 0.23 for daclizumab 300 mg. This represented reductions of 54% and 50%, respectively, in the rates of relapse, which were significant in comparison with placebo.

The percentage of patients who remained relapse free was 81% for daclizumab 150 mg and 80 % for daclizumab 300 mg; both rates were significantly better than for placebo (64%).

The percentage of patients with 3-month confirmed disability progression was 5.9% for the 150-mg dose, 7.8% for the 300-mg dose, and 13.3% for placebo. This was a "surprising result considering this was only a 52-week study [of] the impact of daclizumab on disability progression," Dr. Giovannoni said.

He and his coinvestigators also observed quality of life improvements with daclizumab treatment on physical scores on the Multiple Sclerosis Impact Scale–29, compared with placebo.

Results of the MRI substudy showed a significant 69%-78% reduction in new or enlarging GdE lesions between weeks 8 and 24 of the study in patients treated with daclizumab versus placebo, and a 79%-86% reduction in new or enlarging GdE lesions by the end of the 1-year study.

Adverse events occurred more often among patients in the daclizumab groups (72%-76% vs. 28% with placebo), but any serious event was more likely to occur in patients randomized to placebo (27% vs. 16%-18% for daclizumab).

One death potentially related to treatment occurred in the daclizumab arm. This was due to a complication of a psoas abscess occurring in a patient recovering from a serious cutaneous adverse event.

"The results of this trial have informed the ongoing [clinical trials] program, and monitoring and treatment algorithms have been put in place to mitigate any safety concerns," Dr. Giovannoni said.

Another two clinical studies of daclizumab are currently ongoing – an open-label, multicenter extension of the SELECT study and the phase III DECIDE trial. This latter trial is comparing up to 144 weeks of treatment with daclizumab against interferon beta-1a (Avonex) in about 1,500 patients with relapsing-remitting multiple sclerosis. Primary data from the trial are unlikely to be available until late 2013.

The SELECT study was supported by Biogen Idec and Abbot Biotherapeutics. Dr. Giovannoni disclosed receiving research support and/or consulting fees from Bayer Healthcare, Biogen Idec, and other manufacturers of MS therapies.

AMSTERDAM – Daclizumab reduced the rate of relapse and the rate of disability progression in patients with relapsing-remitting multiple sclerosis in a 1-year, placebo-controlled phase II trial .

The novel immunomodulatory therapy also reduced the number of new brain lesions detected on MRI while producing a very low rate of treatment discontinuation and a low rate of injection site reactions, [which is] consistent with a very good tolerability profile," study investigator Dr. Gavin Giovannoni said at the joint triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

Daclizumab (Zenapax) is a humanized monoclonal antibody targeted against the CD25 alpha subunit of the interleukin-2 receptor. It is currently approved for the prophylaxis of acute organ rejection in patients receiving renal transplants. Although it is not clear how daclizumab works, it is thought that the drug reduces the number of activated T cells and increases natural killer cell proliferation (J. Immunol. 2010;185:1311-20).

In the multicenter, double-blind SELECT study, 600 patients were randomized to receive subcutaneous injections of one of two doses of daclizumab (150 mg or 300 mg) or placebo every 4 weeks for up to 1 year.

Patients were eligible for the study if they had a diagnosis of relapsing-remitting multiple sclerosis confirmed with McDonald 2005 criteria and at least one relapse in the past 12 months with brain MRI consistent with MS or gadolinium-enhanced (GdE) lesion activity in the 6 weeks prior to randomization.

In an MRI substudy, 309 patients underwent monthly brain scans while the remaining study population underwent MRI at four time points: before treatment, 24 weeks after randomization, 26 weeks after randomization, and then 52 weeks after randomization. At baseline, the two groups of patients had a median age of 35-37 years and a median time since diagnosis of 2-3 years. About three-quarters of patients were treatment naive and had experienced 1.3-1.4 relapses in the past year. However, 52% of patients randomized to 150 mg daclizumab had one or more GdE lesions – a higher rate than that seen in either the 300-mg daclizumab or placebo groups (36% and 44%), reported Dr. Giovannoni of Queen Mary University in London.

At 1 year, the annualized relapse rate was 0.46 for placebo, 0.21 for daclizumab 150 mg, and 0.23 for daclizumab 300 mg. This represented reductions of 54% and 50%, respectively, in the rates of relapse, which were significant in comparison with placebo.

The percentage of patients who remained relapse free was 81% for daclizumab 150 mg and 80 % for daclizumab 300 mg; both rates were significantly better than for placebo (64%).

The percentage of patients with 3-month confirmed disability progression was 5.9% for the 150-mg dose, 7.8% for the 300-mg dose, and 13.3% for placebo. This was a "surprising result considering this was only a 52-week study [of] the impact of daclizumab on disability progression," Dr. Giovannoni said.

He and his coinvestigators also observed quality of life improvements with daclizumab treatment on physical scores on the Multiple Sclerosis Impact Scale–29, compared with placebo.

Results of the MRI substudy showed a significant 69%-78% reduction in new or enlarging GdE lesions between weeks 8 and 24 of the study in patients treated with daclizumab versus placebo, and a 79%-86% reduction in new or enlarging GdE lesions by the end of the 1-year study.

Adverse events occurred more often among patients in the daclizumab groups (72%-76% vs. 28% with placebo), but any serious event was more likely to occur in patients randomized to placebo (27% vs. 16%-18% for daclizumab).

One death potentially related to treatment occurred in the daclizumab arm. This was due to a complication of a psoas abscess occurring in a patient recovering from a serious cutaneous adverse event.

"The results of this trial have informed the ongoing [clinical trials] program, and monitoring and treatment algorithms have been put in place to mitigate any safety concerns," Dr. Giovannoni said.

Another two clinical studies of daclizumab are currently ongoing – an open-label, multicenter extension of the SELECT study and the phase III DECIDE trial. This latter trial is comparing up to 144 weeks of treatment with daclizumab against interferon beta-1a (Avonex) in about 1,500 patients with relapsing-remitting multiple sclerosis. Primary data from the trial are unlikely to be available until late 2013.

The SELECT study was supported by Biogen Idec and Abbot Biotherapeutics. Dr. Giovannoni disclosed receiving research support and/or consulting fees from Bayer Healthcare, Biogen Idec, and other manufacturers of MS therapies.