Sanofi, the French pharmaceutical company, has officially announced it will appeal the Food and Drug Administration’s (FDA) rejection of the multiple sclerosis (MS) drug, Lemtrada. The Sanofi drug was set to launch in what is considered the world’s biggest drug market, but its attempts were quickly halted over concerns with Lemtrada’s efficacy and safety. The biotechnology group, Genzyme, controlled by Sanofi-Aventis, was accused by the agency for not providing substantial evidence that the benefits of the drug outweighed its “serious adverse effects,” according to a press release.
“We strongly believe that the clinical development program, which was designed to demonstrate how Lemtrada compares against an active comparator as opposed to placebo, provides robust evidence of efficacy and a favorable benefit-risk profile,” said Genzyme President and CEO, David Meeker, M.D. “This evidence was also the basis for the approvals of Lemtrada by other regulatory agencies around the world.”
Patients who suffer from the immune-mediated disease may lose their ability to walk or speak clearly due to the belief that the body’s immune system attacking its own tissues. The Mayo Clinic says this process destroys myelin, the fatty substance that coats and protects nerve fibers in the brain and spinal cord, which leads to the overall inflammation and deterioration of the nerves themselves.
Lemtrada aims to reduce the annualized relapse rates and the disability progression of MS. The monoclonal antibody in the MS drug — alemtuzumab — works by selectively targeting CD52, a protein rich on T and B cells, thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab depletes the circulating T and B cells and then is immediately followed by the onset of a distinctive pattern of T and B cell repopulation. The rebalancing of the immune system is said to be a method which could potentially reduce the effects of MS on the body. The drug is meant to be taken intravenously, despite the fact that it is an annual treatment. Typically, patients take one dose over five days and then another a year later, over three days.
Currently, Lemtrada is approved in the EU, Canada, and Australia but has yet to gain FDA approval due to concerns raised by agency reviewers in November. The FDA safety reviewers addressed the potentially fatal safety issues of the drug, such as the increased risk of cancer, diabetes, and autoimmune diseases. The incidences of thyroid cancer in patients taking Lemtrada were found to be alarming and raised safety flags for reviewers. The thyroid cancer rate for U.S. female patients taking alemtuzumab in clinical trials was 129.6 cases per 100,000 persons, compared to the National Cancer Institute's rate 18.2 out of 100,000 persons.
Dr. Evelyn Mentari, FDA safety reviewer, recommended the FDA not approve Genzyme's application to market alemtuzumb for relapsing forms of MS due to the numerous safety flags the drug raised in November. However, if the MS drug were approved, Dr. Mentari suggested it to “be used exclusively in a setting capable of treating life-threatening emergencies and that the drug be used with caution in “patients with a history of cardiac disease.”
The concern of serious side effects for MS drugs does not only pertain to Lemtrada. Sanofi’s Aubagio — the company’s existing MS treatment — contains warnings on the risk of liver problems and birth defects, The Wall Street Journal reports. Aubagio was approved by the FDA in September 2012 for patients with relapsing forms of MS after clinical studies have shown the oral tablet was successful in previous clinical trials.
In the competitive market for MS treatments, Sanofi may face difficult challenges ahead before receiving approval from the FDA. Sanofi's U.S. sales had been on the decline primarily due to generic competition on products like blood thinner Plavix, sleep drug Ambien, and allergy meds Allegra and Nasacort, in the third-quarter 2013, according to Medical Marketing & Media.
MS affects approximately 400,000 Americans and an estimated 2.5 million people worldwide, says the Multiple Sclerosis Association of America. Most people with MS experience their first symptoms and are diagnosed between the ages of 15 and 50, most commonly seen in women. Symptoms of the debilitating disease include numbness or weakness in one or more limbs, double vision or blurring of vision, tingling or pain in parts of the body, and fatigue.
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