FDA staff question safety of Sanofi's multiple sclerosis therapy Lemtrada

In briefing documents released Friday ahead of an FDA advisory committee meeting on November 13, agency staff said that "multiple serious and potentially fatal safety issues" associated with Sanofi's Lemtrada (alemtuzumab) may outweigh the efficacy of the multiple sclerosis drug unless it demonstrated "substantial clinical benefit." FDA reviewer John Marler remarked that "the certainty of the risks of potentially lifelong hypothyroidism...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."

The FDA accepted a filing from Sanofi's Genzyme unit in January seeking approval of the injectable therapy for the treatment of relapsing MS. The agency had previously issued a refuse-to-file letter regarding the application, requesting that Genzyme modify the data presentation in the application. The regulator is expected to decide whether to approve Lemtrada by the end of the year.

Genzyme previously reported that in the CARE-MS I and CARE-MS II trials, Lemtrada was significantly more effective in reducing annualised relapse rates than Merck KGaA's Rebif (interferon beta-1a). Additionally, the CARE-MS II trial revealed that Lemtrada substantially slowed the accumulation of disability in patients compared to Rebif. However, Marler argued that the company's decision to disclose which patients received the therapy, and the subjective measure by which the drug's effectiveness was measured, may have skewed the results.

In response, Sanofi said it was unable to keep that information confidential because of the differences in dosing Lemtrada, which is given annually, and dosing in the other arms of the studies. The drugmaker indicated that follow-up results showed findings consistent with the clinical trial data, adding "our company is confident that Lemtrada offers an important step forward in the way physicians and patients will think about treating multiple sclerosis." However, Kepler Cheuvreux analyst Fabian Wenner said the briefing documents are "like a death sentence." He noted that "it isn’t what everyone expected, an issue with the safety," adding "it seems to be a more fundamental issue here." For further analysis, see ViewPoints: Can Sanofi convince FDA on the benefits of Lemtrada?

Sanofi gained Lemtrada via its $20.1-billion acquisition of Genzyme in 2011, with shareholders who hold a contingent value right set to receive cash payments upon the approval of the drug. Bayer will co-promote the therapy, which analysts project will generate revenue of $691 million in 2017, and receive royalties on sales. Lemtrada was cleared in Europe in September for the treatment of adults with relapsing remitting MS whose active disease is defined by clinical or imaging features. For related analysis, read Physician Views Poll Results – Sanofi's new multiple sclerosis treatment Lemtrada to be used more widely than expected? and ViewPoints: Sanofi prices Lemtrada comparably to other MS therapies, but at notable premium to previous incarnation as Campath.

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