Sanofi multiple sclerosis drug may have too many risks, FDA warns

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WASHINGTON — Sanofi's multiple sclerosis treatment Lemtrada may not offer enough benefit to patients to outweigh risks including cancer, U.S. regulators said Friday. The French drugmaker's shares fell.

Lemtrada's "serious and potentially fatal safety issues," which include the risk of autoimmune and thyroid diseases, may make the medicine too dangerous to approve unless there is substantial clinical benefit shown, Food and Drug Administration staff said in a report. Agency reviewers also questioned whether Sanofi conducted adequate trials to prove the annual infusion works.

"That's like a death sentence," said Fabian Wenner, an analyst with Kepler Cheuvreux in Zurich. "It isn't what everyone expected, an issue with the safety. It seems to be a more fundamental issue here."

Lemtrada, approved in Europe earlier this year, was at the center of Paris-based Sanofi's $20 billion acquisition of Genzyme Corp. in 2011. Shareholders who have contingent value rights stand to receive cash payments if Lemtrada is approved. Bayer plans to co-promote Lemtrada and will receive payments based on sales.

"The certainty of the risks of potentially lifelong hypothyroidism, serious infusion reactions, melanoma and other malignancies, Graves' ophthalmopathy and other autoimmune disorders, and prolonged increased susceptibility to infection may not be balanced by the uncertainty that exists in the limited evidence of the potential clinical benefits from clinical trials that were not well-controlled," FDA drug reviewer John Marler wrote in the report.

An advisory panel on Nov. 13 will discuss whether to recommend the drug's approval. The FDA is expected to decide whether to clear the medicine for treating relapsing MS patients by the end of the year.

Sanofi did submit trial evidence that showed Lemtrada had a significant benefit, though the company's decision to not keep secret which patients were taking the medicine and the subjective nature of determining whether the therapy was working may have skewed results, Marler said.

Sanofi said it was unable to keep that information confidential because of the differences in how the drugs, Lemtrada and an older treatment, were given, including annual dosing compared with three times a week. Follow-up data showed findings consistent with clinical trial results, Sanofi said in an e-mailed statement.

"Our company is confident that Lemtrada offers an important step forward in the way physicians and patients will think about treating multiple sclerosis," Sanofi said.

Sanofi fell less than 1 percent to 77.94 euros at 4:21 p.m. Paris time. The contingent value rights linked to the Genzyme acquisition dropped 68 percent to 65 cents in New York trading.

Genzyme stockholders had received one right entitling the owner to additional fees of as much as $14 per CVR by the end of 2020 if Sanofi met certain goals, most of them tied to the approval and sale of Lemtrada.

Lemtrada won European Union approval in September and the active ingredient alemtuzumab was cleared by the FDA in 2001 to treat a certain form of leukemia, though it is no longer for sale.

The drug may generate sales of $691 million in 2017, according to the average of eight analysts' estimates compiled by Bloomberg.

Multiple sclerosis is a debilitating disease that attacks the central nervous system. Relapses, or flare-ups, are episodes of worsening neurologic function, according to the National MS Society.

Relapsing MS patients have 10 treatment options now with varying degrees of efficacy at reducing relapses, said Robert Fox, medical director at the Cleveland Clinic's Mellen Center for Multiple Sclerosis. Biogen Idec Inc.'s Tysabri is linked to risk of serious brain infections. Fox compared Lemtrada to Tysabri.

"This is not a first-line drug given the risks inherent in the drug," Fox said in an interview. "It is a reasonable option for those who haven't responded to other treatments." Other treatments for relapsing multiple sclerosis include another Sanofi drug Aubagio, a daily pill; Biogen's Tecfidera, a twice-daily pill approved in March; and Teva Pharmaceutical Industries Ltd.'s Copaxone, a subcutaneous injection. Lemtrada is administered through two courses of shots given a year apart.

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Bennett reported from Geneva. Catherine Larkin contributed from Chicago.

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