In a major blow to Cambridge drug maker Genzyme, the Food and Drug Administration formally rejected a key multiple sclerosis treatment, Lemtrada, calling into question the integrity of clinical trials and citing the risk of potentially serious side effects.
A Genzyme executive said the company plans on appealing the FDA ruling and is considering steps that could include meeting with federal regulators prior to a formal appeal.
"We are extremely disappointed by and disagree with the FDA's conclusion," said Bill Sibold, Genzyme senior vice president and head of the MS business. "Multiple sclerosis is a devastating disease and MS patients need options."
The decision Monday essentially codifies weeks of unfavorable reviews from the US regulator, including an alarming report in November from an FDA panel of medical advisers that warned of rashes, bleeding, and even thyroid cancer as possible side effects.
Even so, Lemtrada has been approved in the European Union, Australia, and Canada, leaving Genzyme puzzled by how the FDA could rule so differently, Sibold said.
"We've had positive outcomes with other regulatory agencies around the world that looked at the exact same results and came to different conclusions."
While the drug has been approved for use in 30 other countries, concerns about Lemtrada first surfaced in November in the United States when regulators raised safety questions. Until then, it was widely accepted that the FDA would follow Europe's lead and approve Lemtrada, giving Genzyme's parent company, French drug maker Sanofi SA, a major foothold in the American drug market.
But Genzyme and Sanofi revealed Monday that the FDA said Lemtrada was "not ready for approval" because the companies had "not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects."
The FDA would not comment on the decision or the appeal process.
It's unusual for the FDA to reverse decisions on drug approvals, meaning that Genzyme might have to conduct new trials of Lemtrada in patients. That could delay the drug's arrival on the American market for at least two years, said Damien Conover, an analyst at Morningstar.
Conover said that Sanofi is big enough to absorb the extra cost. And the delay does not appear to have hurt its stock Monday. Shares were up 0.17 percent, closing at $52.89.
Investors should have expected this, Conover said, given the red flags from the advisory panel in November. At the time a drug reviewer also said that Lemtrada tests "were not well controlled."
Genzyme has defended the drug against concerns of risks. MS patient groups have also advocated for its approval.
Genzyme has been in development of Lemtrada for the treatment of MS, a disease that affects the central nervous system, for more than a decade. Approximately 1,700 patients have been involved in the trials. Globally, more than 2.3 million people have been diagnosed with multiple sclerosis, including about 400,000 in the United States.
The potential of that market, and the promise of Lemtrada's approval in the United States, was a major attraction for Sanofi, which paid $20.1 billion to acquire Genzyme in 2011. As part of that deal, Sanofi agreed to reward former Genzyme stockholders if the drug achieved certain milestones in the US market regarding approval and sales.
Sanofi said on Monday it does not expect to meet a March 31 milestone that it set for Lemtrada's US approval.
Michael B. Farrell can be reached at email@example.com.