In March of this year, Genzyme’s Michael Panzara, therapeutic area head and group VP for MS and immune diseases, hailed Sanofi’s Lemtrada at the American Academy of Neurology annual meeting in San Diego, citing its “unique approach to disease modification.” Then in September, the drug was approved in the EU for relapsing-remitting MS. Safety concerns unveiled in an FDA briefing document last Friday, however, suggest that it may not be smooth sailing for the drug in the US.

One of the FDA safety reviewers, Evelyn Mentari, MD, noted that “because of serious and potentially fatal safety issues, unless alemtuzumab (Lemtrada) shows substantial clinical benefit, this reviewer recommends that FDA not approve Genzyme’s application to market alemtuzumb for relapsing forms of MS.”

Among numerous safety flags raised, one of the most jarring was the occurrence of thyroid cancer. The National Cancer Institute’s threshold for thyroid cancer in US females is 18.2 out of 100,000 persons; the rate for alemtuzumab female patients seen in clinical trials was 129.6 cases per 100,000 persons—a potential seven-fold increase.

Leerink Swann analyst Seamus Fernandez, in an investor note issued today, wrote that it will be “very challenging” for Sanofi/Genzyme to receive a positive nod from the panel and, similarly, the drug’s chances for a near-term approval “will be extremely challenging.”

The EU approval for Lemtrada was based largely on two clinical trials, and data for these studies has also come into question. John Marler, MD, another one of the FDA medical reviewers, wrote that he “has grave concerns that the failure to blind patients and treating physicians in the open-label design of the trials introduced bias that confounds interpretation of their ostensible results” and that “applicant [Sanofi/Genzyme] has not submitted evidence from adequate and well-controlled studies to support the effectiveness of alemtuzumab for treating multiple sclerosis.”

Dr. Mentari also suggested  that Lemtrada—if it were to be approved—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.”

With MS pill Aubagio earning FDA clearance in 2012 and with Lemtrada on-market in the EU, Genzyme has been talking up its budding “MS franchise.” But the ad-com panelists could throw a wrench into the French drugmaker’s recovery plan. As recently as third-quarter 2013, Sanofi’s US sales had been on the decline, mainly due to generic competition on products like blood thinner Plavix, sleep drug Ambien, and allergy meds Allegra and Nasacort.

The FDA advisory committee is set to give its recommendation this Wednesday, and the agency is expected to make a final decision before the end of the year.