December 30, 2013
FDA Rejects French MS Drug For ‘Serious Adverse Effects’
The Food and Drug Administration (FDA) has rejected French drugmaker Sanofi’s multiple sclerosis (MS) treatment called Lemtrada, the company announced on Monday. The rejection is considered a serious blow to the company, which had the drug recently approved by other regulatory bodies.
The FDA did not approve the drug on the grounds that the Sanofi-owned developer Genzyme had not demonstrated that its medical benefits offset its "serious adverse effects,” Sanofi said in a statement.
“FDA has also taken the position that one or more additional active comparator clinical trials of different design and execution are needed prior to the approval of Lemtrada,” the company added.
Sanofi went on to say that it disagreed with the FDA ruling and planned to appeal it. The same drug was approved by EU regulators in September as well as by Canadian and Australian regulators more recently.
Alemtuzumab, the active ingredient in the drug, targets a specific immune system protein and reorganizes immune system cells. The result is a significant suppression of inflammatory activity in patients with MS.
Clinical trials showed that alemtuzumab was better than beta-interferons, a standard drug for relapsing-remitting MS. Some clinical evidence even found that it slowed the progression of disability. While one of the trials showed progression was significantly slower, another trial failed to show statistical significance.
The trials also found significant side effects. In both trials, over 18 percent of patients experienced adverse thyroid events – including thyroid cancer – related to the new drug, compared to 5.4 percent of the control patients taking interferon. Other side effects included blood-clotting problems and inflammation of the lung tissue.
Panel member Dr. Evelyn Mentari expressed serious reservations about approving the drug.
"These safety concerns cannot be prevented by monitoring or prophylactic measures," Mentari said. "Because the post-marketing setting involves a broader range of patients and less structured monitoring, there may be an increased risk of serious and fatal outcomes."
Despite these side effects, an FDA advisory panel said in November that the drug was effective for reducing relapses and safety issues should not prevent approval. However, panel members said the drug's effect against disability evolution remained unproven. Both the FDA panel and the officials that rejected the drug expressed concerns that participants in the clinical trials knew which drug they were taking – potentially tainting the results.
Even with the clinical trials’ many flaws, experts were still calling for the FDA to eventually approve the drug.
"While there are very valid concerns about the data interpretation from the trial and safety profile of the drug, there are reasonable levels of efficacy data to support its approval," Benjamin Greenberg, a neurology professor at the University of Texas Southwestern Medical Center in Dallas told MedPage Today.
"Given its unique and profound mechanism of action, this drug will have potential uses for specific patients who have the highest need for efficacious interventions,” Greenberg added.
"Most of the neurologists in the MS community want this medication to be approved,” added Dr. Neil Lava, a neurologist at Emory University's MS Center in Atlanta. “It will be an excellent addition to our MS drug armamentarium.”