The future of a key multiple sclerosis drug developed by Cambridge biotech Genzyme was put in doubt Friday after federal regulators suggested it could be too dangerous to approve because of what they believe are the treatment’s limited benefits.
The drug, Lemtrada, was pivotal to sealing French drug maker Sanofi SA’s $20.1 billion purchase of Genzyme Corp. in 2011. Sanofi is counting on it and other new treatments to rejuvenate the global drug giant’s sales.
Until Friday, approval from the Food and Drug Administration seemed likely, especially since European regulators in September signed off on the sale of Lemtrada overseas. But an FDA staff report — prepared in advance of a Wednesday advisory panel meeting to consider whether to recommend Lemtrada’s sale in the United States — indicates Genzyme now faces a major hurdle.
The report said the drug has “serious and potentially fatal safety issues,” including a risk of cancer. While such staff reviews are not binding, advisory panels — made up of prominent medical specialists — give them significant consideration.
“That’s like a death sentence,” Fabian Wenner, an analyst with Kepler Cheuvreaux in Zurich, said of the report. “It isn’t what everyone expected, an issue with safety. It seems to be a more fundamental issue here.”
Sanofi said Friday that it remains confident in Lemtrada’s effectiveness and safety and is eager to make a case next week for the drug’s approval.
The shadow over the MS treatment marked the fourth major setback in recent weeks for a Massachusetts biotechnology company.
On Thursday, Ariad Pharmaceuticals Inc. laid off 160 people, about 40 percent of its US workforce, after the Cambridge company pulled its leukemia pill from the market because some patients taking the drug suffered blood clots and heart problems.
ImmunoGen Inc., a Waltham biotech, on Tuesday stopped a mid-stage study of a drug to treat small-cell lung cancer after it was linked to infections and infection-related deaths.
Earlier, Vertex Pharmaceuticals Inc., which is scheduled to move from Cambridge to an expansive headquarters on the Boston waterfront next month, cut 370 jobs, including 175 in Massachusetts, because of a dramatic drop in sales of its hepatitis C drug.
In the report on Genzyme’s Lemtrada, FDA drug reviewer John Marler detailed a litany of conditions and complications that could be caused by the MS treatment. He also called into question the way clinical trials of the drug were conducted.
“The certainty of the risks of potentially lifelong hypothyroidism [a thyroid condition], serious infusion reactions, melanoma, and other malignancies, Grave’s ophthalmopathy [a thyroid-related eye disease] and other autoimmune disorders and prolonged increased susceptibility to infection may not be balanced by the uncertainty that exists in the limited evidence of potential clinical benefits from clinical trials that were not well-controlled,” Marler wrote.
Specifically, the FDA questioned why Sanofi did not try to keep patients in trials from knowing whether they were taking the medicine, suggesting that may have skewed results.
In response, Sanofi defended how the drug was tested on patients with MS, a debilitating disease that attacks the central nervous system. The company said it was difficult to keep the test entirely blind because of differences in how Lemtrada and the drug it was compared with are administered.
Bo Piela, a Genyzme spokesman, said the company also sought the FDA’s advice on how to set up the studies.
“There are, of course, issues that will be considered by the advisory committee and we look forward to our discussion with them,” Piela said in a statement.
But some industry analysts wonder whether Sanofi and Genzyme can overcome such serious questions.
Former Genyzme stockholders will be closely watching next week’s advisory panel session. Under terms of the sale agreement that brought the local pillar of the biotechnology industry into the Sanofi fold, they are to receive the first of several potential milestone payments if the medicine is approved for sale in the United States by the end of this year.
Sanofi Chief executive Christopher A. Viehbacher earlier noted he had promised former Genzyme leader Henri Termeer a bottle of French wine if the milestone payments turned out to be especially generous.
“The way Lemtrada’s developing,” he said at the time, “it may cost me a very good bottle of wine.”
Viehbacher also said then that Genzyme has been among the fastest-growing divisions of the global drug maker, with sales up by more than 25 percent in the first half of 2013.
European approval of the drug was especially significant because regulators said Lemtrada could be taken by patients newly diagnosed with MS, not just those who had tried other treatments. The company is hoping for such a finding in the United States.
Lemtrada’s European competition includes Tysabri, made by another Massachusetts biotech mainstay, Cambridge-based Biogen Idec Inc. In Europe, Tysabri can only be used by patients whose MS symptoms continued to progress even after other treatments, which gives Lemtrada an advantage.
In August, European regulators signed off another MS drug, Aubagio, a pill that was developed by Sanofi but turned over to the Genzyme division. Aubagio was approved by the FDA for US sale last September, giving Genzyme its first entry into the MS market.
The company is best known for developing expensive drugs to combat rare genetic disorders such as Gaucher and Fabry diseases, which affect a small number of people worldwide.