Guarded Optimism for Experimental MS Drug

Alemtuzumab Appears to Repair Damage to Brain in Patients With MS

Medically Reviewed by Louise Chang, MD on October 22, 2008
From the WebMD Archives

Oct. 22, 2008 -- An experimental multiple sclerosis drug proved to be much more effective for the treatment of early MS than a widely used treatment in a study, but the efficacy came at a price.

Patients with early relapsing-remitting MS treated with the drug alemtuzumab had far fewer relapses and evidence of MS progression than patients treated with the approved treatment, interferon beta-1a.

Remarkably, some patients who got the experimental drug had less disability associated with their disease three years after starting the study than at entry, raising hopes that the treatment might stop the disease in its tracks before it progresses to its crippling stage.

1 Alemtuzumab Death

But nearly one in four alemtuzumab-treated patients also developed treatment-related thyroid complications.

Even more troubling, 3% of the patients developed a potentially life-threatening autoimmune condition, which resulted in the death of one patient.

Study co-author Alasdair Coles, PhD, tells WebMD that phase III trials will soon be under way to determine if the benefits of alemtuzumab outweigh the risks in patients with early relapsing-remitting multiple sclerosis.

According to the National MS Society, relapsing-remitting MS accounts for 85% of people who are first diagnosed with MS.

The study appears in the Oct. 23 issue of TheNew England Journal of Medicine.

"The phase II results are very exciting, but this is not ready for routine use," he says. "We need to know more about the long-term effectiveness and adverse effects. That is our challenge over the next few years."

Once-a-Year Treatment

Developed by Cambridge University researchers several decades ago, alemtuzumab was the first monoclonal antibody made for use in humans, and it is approved for the treatment of chronic lymphocytic leukemia (CLL).

It works by targeting and destroying certain immune cells, which normally protect against infection but are believed to be damaged in MS and other autoimmune diseases, resulting in the destruction of healthy tissue.

Cambridge researchers first tried the drug in patients with advanced multiple sclerosis, with little success.

The newly reported phase II trial included only patients with early, relapsing-remitting multiple sclerosis who had not been treated with other MS drugs.

Between December 2002 and July 2004, 334 patients in Europe and the United States were enrolled in the study.

About a third of the patients were treated with the first-line therapy interferon beta-1a, given by injection three times a week. The remaining patients were treated with alemtuzumab, given by infusion in once-a-year cycles.

The initial cycle involved four-hour infusions given daily for five days. Twelve months later, most patients got a second, three-day course of the drug.

Response 'Unprecedented'

Three years after the trial was initiated, treatment with the experimental drug was associated with dramatic reductions in clinical relapses and a reduction in inflammatory activity (as seen on brain MRI scans) compared to the interferon treatment.

But Cole says the fact that the experimental treatment actually appeared to reverse damage to brain tissue caused by MS is the most exciting finding from the study.

"That is unprecedented and very big news," he says. "Another important part of the strategy involves treating patients very early in the course of the disease with the most effective agents we have."

The study was funded by the drug companies Genzyme and Bayer Schering Pharma AG, which own the marketing rights to alemtuzumab.

In a Wednesday morning news conference, Genzyme Medical Director Susan Moran, MD, addressed the death that occurred during the study.

The patient died from an autoimmune-mediated blood condition known as idiopathic thrombocytopenic purpura (ITP). Moran said the death could have been avoided if ITP had been recognized as an adverse effect of the treatment.

"Unfortunately, the patient had symptoms of ITP but did not seek medical attention prior to diagnosis because this was not recognized as an adverse event," she says.

Once the risk was known, patients in the study were monitored closely for ITP. Five additional cases were identified, and all were managed with treatment.

Close Monitoring Essential

Moran says all the patients enrolled in the phase III trial and all patients who end up taking the drug if it is approved for MS will have to be monitored closely for this adverse effect.

Researchers are also working on ways to identify patients who are most likely to develop ITP before treatment and to identify the MS patients who are most likely to benefit from early, aggressive therapy.

In an editorial published with the study, neurologist and longtime MS researcher Stephen L. Hauser, MD, writes that it is not yet clear if alemtuzumab will prove to be an acceptable first-line treatment for early MS.

Hauser is chief of neurology at the University of California, San Francisco Medical Center.

"Taken together, the toxic effects associated with alemtuzumab considerably dampen any enthusiasm for its routine use in patients with multiple sclerosis until more is known about its long-term safety and sustained efficacy," he writes.

John Richert, MD, of the National Multiple Sclerosis Society (NMSS), tells WebMD that it is increasingly clear that aggressive treatment early in the course of disease is a better strategy than waiting until MS progresses.

He agrees that alemtuzumab's role in MS treatment remains to be determined.

Richert is vice president for research and clinical programs for NMSS.

"This may be the breakthrough drug we are looking for, but we won't know that until the phase III study is done," he says.

Show Sources


The New England Journal of Medicine, Oct. 23, 2008; vol 359: pp 1786-1801.

Alasdair J. Coles, PhD, University of Cambridge School of Clinical Medicine, Cambridge, England.

Stephen L. Hauser, MD, University of California, San Francisco.

John Richert, MD, executive vice president for research and clinical programs, National Multiple Sclerosis Society.

Alastair Compston, PhD, head of the department of clinical neurosciences, University of Cambridge, Cambridge, England.

Susan Moran, MD, medical director, Genzyme Corp.

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