Merck-Serono's FDA holdup with cladribine could be due to need for additional trial, industry sources speculate




2010-02-22 Pharmawire


Intelligence Details


Merck-Serono's hold-up with the FDA over oral multiple sclerosis drug cladribine's refuse-to-file letter could be due to the request for an additional trial, according to an industry source and neurologists.
According to a medical director at a competing company, the FDA and EMEA usually require two Phase III trials that test an agent over a two-year period. The EMEA also requires a trial that has an active comparator, he said. "The FDA would like two Phase III trials over a duration of two years," he noted.
The company's CLARITY trial was a randomized, double-blind, placebo-controlled Phase III trial that was conducted over a two-year period. The primary endpoint of the study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints, proportion of subjects qualifying relapse-free and disability progression at 96 weeks.
A spokesperson for Merck-Serono said it is company policy not to discuss the details of its interactions with health authorities.
An FDA spokesperson -- who said she consulted with Dr Russell Katz, the director of neurology at the FDA --noted in an e-mail that two studies would be the agency's "typical standard" for new drugs. "Unless there is a compelling reason to apply another standard (the law permits approval on the basis of a single well controlled trial and confirmatory evidence, a standard we have, but rarely, invoked) we would require two studies."
The spokesperson declined to comment on the cladribine situation specifically.
One neurologist said the refuse to file letter might not involve a simple issue, because the company did not disclose a timeline as to when it would respond to the FDA. He said when Acorda (NASDAQ:ACOR) received a refuse-to-file letter from the agency in March 2009 for Fampridine-SR, the company resubmitted its new drug application about three weeks later. Merck-Serono received its refuse-to-file letter on 1 December. The neurologist speculated that the delay is because the agency had a problem with the single trial.
"It’s becoming more and more clear that FTY720 will be out on the market before cladribine," the neurologist said, referring to Novartis' Phase III oral MS drug which he claimed may also need a second trial with a lower dose. A second neurologist concurred that the delay could be the request for an additional trial.

by Kimberly Ha in New York