Interim Results from Campath® (Alemtuzumab) Trial Announced

September 23, 2005

On September 16, 2005, Genzyme Corporation and Schering AG Germany announced the interim results of a phase II trial comparing Campath® (alemtuzumab) with Rebif® (interferon beta-1a). These results came from an efficacy (looking at effectiveness) and safety interim analysis, following the completion of one year of treatment in a planned three-year trial.

Campath is a humanized monoclonal antibody that binds to a specific target (CD52) on cell surfaces, directing the body to destroy potentially damaging cells within the immune system. Large doses of this drug are approved in the United States to treat cancer. A much smaller dose is being used in the trials for MS. For these studies, Campath is administered in annual intravenous (directly into the vein) infusion regimens (a five-day course of doses is given the first year; a three-day course of doses is given during the second year and beyond). Rebif is given three times per week via subcutaneous (under the skin) injections.

This phase II trial has enrolled 334 patients with active relapsing-remitting MS and is being conducted at 49 medical centers in the United States and Europe. The trial is randomized (participants are assigned to the treatment groups randomly to minimize the differences between the treatment groups) and open label ( participants and treating medical professionals both know which drug each group is receiving).

The trial has three treatment arms: low-dose Campath, high-dose Campath, and regular dose Rebif. The two primary endpoints to measure effectiveness were: (1) the rate of relapse of MS symptoms and (2) the time to progression of clinically significant disability (time to Sustained Accumulated Disability at six months as measured by the Expanded Disability Status Score [EDSS]).

The assessments to determine: (1) whether or not a patient was experiencing an MS relapse, as well as (2) the EDSS of each participant, was performed by blinded medical professionals. This means that the evaluating physicians did not know which drug the participant was taking.

According to the companies’ announcement, the one-year interim analysis showed a 75 percent reduction in relapse rate and a 60 percent reduction in the risk for progression of clinically significant disability for individuals treated with Campath, as compared to those receiving Rebif. Serious adverse events, however, occurred in two participants on Rebif, four participants on the low dose of Campath, and five participants on the high dose of Campath.

Three documented cases of idiopathic thrombocytopenic purpura (ITP) occurred (causing a low platelet count with the potential for abnormal bleeding) – two in the high-dose Campath group and one in the low-dose Campath group. One of these three cases resulted in death; the other two individuals affected are responding to treatment. Symptoms of ITP include easy bruising and the appearance of small red spots (tiny hemorrhages) on the arms and legs, unrelated to any abrasions or injections. The companies’ representatives explain that the patient who died was unaware of these symptoms and passed away before treatment could be administered.

In response to these adverse events, Genzyme Corporation and Schering AG Germany state that they are implementing a series of safety provisions and have consulted with the United States Food and Drug Administration (FDA) in an effort to protect patient safety. Until all safety provisions are in place, the companies have temporarily suspended the dosing of Campath in this study.

Readers should note, however, that nearly all of those participating in the study have already received their second dose of Campath, and would not be due for another dose for up to one year; during this time, they continue to be evaluated as part of the study. Additionally, the higher dose does not appear to offer any advantage over the lower dose, so the companies will no longer use the higher dose (provided that Campath is reinstated, both Campath treatment arms will be on the low dose for the remainder of the study).

Regarding other adverse events, two participants taking Campath developed Graves’ Disease (a treatable thyroid condition). In an earlier pilot study with Campath and MS, as many as one-third of the treated participants developed Graves’ Disease. This side effect has appeared as early as five months into treatment, but most often will develop during the second year of treatment (at 18 months on average). In an effort to minimize the risk, the present study used exclusion criteria to select a population at a reduced risk of developing Graves’ Disease. Anyone with a history of thyroid problems, or who showed any evidence of abnormal thyroid function according to lab results at entry, was excluded from the trial. Trial representatives speculate that this could explain why the incidence of Graves’ Disease has been so low.

The companies are not disclosing details about the adverse events which were experienced by six other study participants, except to say that none of the adverse events were unexpected. Genzyme representatives did confirm that no cases of progressive multifocal leukoencephalopathy (PML) have occurred. This potentially fatal disorder has been observed in three patients taking Tysabri® (natalizumab) in separate trials.

MSAA Vice President and Chief Medical Officer Dr. Jack Burks explains, “Campath is not FDA approved at this time for the treatment of MS. This treatment is still being studied to determine its effectiveness and safety in individuals with MS. While these early results on efficacy are encouraging, patients needing treatment today should not delay being treated with currently available therapies, if advised by their treating MS neurologist. I recommend that individuals discuss the implications of these interim study results with their physician if they have any questions.”

Anyone in need of additional information about MS and its treatments may contact MSAA's Helpline consultants by calling (800) 532-7667, Monday through Thursday, 9:00 am to 8:00 pm, eastern time, and Friday, 9:00 am to 5:00 pm, eastern time. Media questions should be directed to Andrea Borkowski at (800) 532-7667, ext. 123.

Written by Susan Wells Courtney, MSAA Senior Writer
Edited by Dr. Jack Burks, MSAA Vice President and Chief Medical Officer

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