Genzyme’s MS drug Lemtrada falls short of FDA requirements.

Drugmaker Genzyme was dealt a major blow last week when its multiple sclerosis (MS) drug Lemtrada was rejected by the Food and Drug Administration (FDA). The FDA ruling cited the need for further trials to demonstrate the drug’s effectiveness and safety. European regulators approved Lemtrada in September 2013.

Lemtrada, also known as Campath-1H or alemtuzumab, has taken a long and winding road to the FDA’s doorstep. “Campath” stands for Cambridge Pathology, where the monoclonal antibodies’ properties were first recognized as a potential treatment for disease.

According to the University of Cambridge, “The original intention was to use alemtuzumab to treat leukemia. But in…1990, Alastair Compston and Herman Waldmann began discussions over the use of alemtuzumab in multiple sclerosis.”

Alemtuzumab was approved for the treatment of chronic lymphocytic leukemia (CLL) in 2001, but it was also studied as a treatment for autoimmune diseases like rheumatoid arthritis, leukemia, and MS.

Although the drug stopped MS relapses, researchers studying alemtuzumab in secondary progressive MS patients saw their condition continue to worsen. To maximize the drug’s benefit, patients would need to be treated earlier in their disease, before nerve damage accumulated.

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The drug’s license changed hands many times before landing in Genzyme’s portfolio in 2004. When Genzyme’s MS trials began to show promise after 2004, neurologists started prescribing it “off label” (for a purpose other than a drug’s FDA-approved intention) to MS patients.

In September 2012, Genzyme, anticipating FDA approval of alemtuzumab for MS under the name Lemtrada, made the controversial decision to pull the drug from the U.S. market. This effectively stopped neurologists from prescribing it for their MS patients.

In to order give people suffering from CLL access to the drug, Genzyme created the “US Campath Distribution Program.” The program allowed leukemia patients to receive Campath for free directly from Genzyme, now owned by pharmaceutical giant Sanofi, with the stipulation that it be used only as directed.

A major sticking point with the FDA is that trials of Lemtrada were not double-blind, which means that the doctors and patients knew which subjects were receiving Lemtrada and which were getting a placebo.

“The FDA has criticised the trials of Lemtrada for not attempting to blind the trial participants and physicians to their treatment and relying on a blinded rater to assess the effectiveness of Lemtrada,” Dr. Alasdair Coles, an academic neurologist, said. “However, it is not possible to blind people to the immediate side-effects of Lemtrada, and all MS trials rely on a blinded rater. I remain confident in the results of these trials.”

The FDA says more clinical trials are required to show that Lemtrada both benefits MS patients and does not cause potentially serious side effects.

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Dr. Coles, Ph.D. FRCP, first author of two papers describing phase 3 trials of alemtuzumab for MS, shared his views on the FDA decision with Healthline.

“It is very disappointing that the FDA have chosen not to approve Lemtrada for the treatment of multiple sclerosis,” said Coles. “This deprives people with multiple sclerosis in the United States of an important treatment option that is available throughout Europe, Canada, and Australia.”

The drug has several side effects, including nausea, fatigue, fever, and a reduction in white blood cells, which weakens the immune system and makes patients more vulnerable to infections. In clinical trials, 30 percent of patients taking Lemtrada developed secondary autoimmune diseases, most often an under-active or overactive thyroid gland. But Coles says it may still be a better option than interferon beta, which can cause flu-like symptoms and cannot be taken while pregnant or breast feeding.

“Lemtrada is not suitable for everyone with multiple sclerosis because it has serious side effects which require careful monitoring. But it is more effective than interferon beta at reducing relapses and disability, and is attractive to those who have aggressive multiple sclerosis or don’t like frequent injections, or who wish to have children,” Coles said.

Genzyme is appealing the FDA decision and may redesign their trials to meet FDA requirements, but for patients who were responding to Lemtrada in clinical trials—as well as those who were taking it off-label—this may come as little consolation.