Two-year interim results from a Phase 2 trial comparing Campath ( Alemtuzumab ) with Rebif ( Interferon beta-1a ) for the treatment of multiple sclerosis have demonstrated statistically significant efficacy of Campath compared to Rebif.
The phase 2 trial randomized 334 patients with active relapsing-remitting multiple sclerosis at 49 medical centers in Europe and the United States.
Patients in the trial were treated with Alemtuzumab at one of two doses ( 12 or 24/mg per day for five days at initial treatment, and three days of re-treatment ), or Interferon beta-1a ( 44 mcg administered three times per week, as indicated in its product label ).
The Alemtuzumab regimen was administered once per year by intravenous infusion, while the Interferon beta-1a regimen was administered three times per week by subcutaneous injection.
The randomized trial compares the safety and efficacy of Alemtuzumab with Interferon beta-1a using two primary endpoints: the rate of relapse of multiple sclerosis symptoms, and the time to progression of clinically significant disability ( time to Sustained Accumulated Disability over six months as measured by Expanded Disability Status Scale [EDSS] ).
Analysis of the first co-primary endpoint showed that patients taking Alemtuzumab at high and low doses experienced at least a 75 percent reduction in the risk for relapse after at least two years of follow up when compared to patients treated with Interferon beta-1a. This difference was statistically significant in favor of the Alemtuzumab patients at both high and low doses, ( p=0.00328 ).
Analysis of the other co-primary endpoint showed that patients taking Alemtuzumab at high and low doses experienced at least a 65 percent reduction in the risk for progression of clinically significant disability when compared to patients treated with Interferon beta-1a. This difference was statistically significant in favor of the Alemtuzumab patients at both high and low doses ( p=0.01194 ).
Dosing of Alemtuzumab in this study was suspended in September 2005 after three patients developed immune thrombocytopenic purpura ( ITP ), a treatable condition in which patients experience a low platelet count as a result of an immune response directed against the platelets.
At that time, most patients had received two cycles of therapy with Alemtuzumab.
Treatment with Rebif in the control arm has continued without interruption.
The trial remains on clinical hold in the United States, and Genzyme is working closely with clinical investigators and regulatory agencies to complete the study and ensure that the risk of ITP is well understood and managed.
To date, a total of six patients have been diagnosed with ITP in this trial.
Other than ITP, serious adverse events related to treatment occurred among four patients treated with the low dose of Alemtuzumab and four treated with the high dose. Two patients treated with Interferon beta-1a experienced serious adverse events related to treatment.
Common non-serious adverse events included infusion reactions in the Alemtuzumab patients and flu-like symptoms in patients using Interferon beta-1a.
The incidence of all thyroid adverse events, including Graves' disease, was less than expected compared to reports in the literature on the use of Campath in multiple sclerosis.
Campath ( Alemtuzumab ), is indicated in the United States for the treatment of B-cell chronic lymphocytic leukemia ( B-CLL ) in patients who have been treated with alkylating agents and who have failed Fludarabine therapy.
In Europe, Alemtuzumab is named MabCampath.
Source: Genzyme, 2006