UPDATED: FDA casts 'fatal' doubts on Sanofi's long-stalled MS drug Lemtrada

Sanofi's ($SNY) multiple sclerosis drug Lemtrada may be too dangerous to warrant FDA approval, agency staff said, potentially damning news for an injection that has slogged through 25 years of back-and-forth development.

The drug is up for a review from the FDA's CNS panel next week, and, in documents filed ahead of the meeting, an agency investigator wrote that unless Lemtrada shows "substantial" clinical benefits, its "serious and potentially fatal safety issues" make it unapprovable. In its pivotal studies, Lemtrada was tied to higher rates of deadly autoimmune diseases, serious infections and treatment-emergent malignancies, the agency said, risks that could outweigh its efficacy in relapsing MS.

Those concerns will undoubtedly take center stage at Wednesday's panel meeting, where agency advisers will vote on whether to recommend the drug for approval. The FDA is not beholden to following the advice of its staff or third-party committees, but an explicit condemnation of a drug's safety profile certainly doesn't bode well.

Lemtrada, a once-a-year intravenous treatment, was a major component of Sanofi's $20 billion deal for Genyzme back in 2011, and its quarter-century development path has seen it change hands and indications again and again. When Genzyme first got hold of the drug in 2004, it was already approved to treat B-cell chronic lymphocytic leukemia, but, seeing a bigger payday down the road, the biotech took it off the market and got to work on MS, transforming the old drug into a high-powered bargaining chip in its protracted buyout talks with Sanofi.

After today's FDA review release, though, analysts are discounting the pharma giant's chances of an approval. Remarked Leerink Swann's Seamus Fernandez: The FDA's comments "were more negative than expected and highlighted key safety concerns, including a potential 7-fold increase in thyroid cancer cited in the supplementary materials as well as significant questions around the quality and validity of the efficacy package from both the statistical and medical reviewers. While only have €200M in 2020 in our model, we believe it will be very challenging for SNY/Genzyme to emerge with a positive panel outcome--but more importantly--we believe a near-term US approval will be extremely challenging." 

Lemtrada won European approval in September, a milestone meant to set the stage for its big U.S. debut. Now, the FDA's safety concerns make a near-term stateside launch look less likely, and, even if all goes according to Sanofi's plan, Lemtrada's years in the lurch have allowed rivals to snap up pole position in MS. Oral treatments like Biogen Idec's ($BIIB) Tecfidera and Novartis' ($NVS) Gilenya lead the way among next-gen therapies, and analysts figure Lemtrada, if approved, would be used only in advanced cases of MS.

- read the FDA documents (PDF)