WASHINGTON U.S. health regulators need more time to review Merck & Co's application to sell sugammadex, an injection designed to reverse the effects of muscle relaxants used during surgery, the company said on Tuesday.
The announcement came after the U.S. Food and Drug Administration canceled a meeting of outside advisers who were scheduled to vote Thursday on whether to recommend the drug be approved. The FDA declined to give an explanation for its unusual last-minute cancellation.
Merck said the FDA needs additional time to assess the results of its recently completed inspection of a clinical trial site that was involved in a study of whether the drug increases the risk of allergic reactions.
In 2008 the FDA declined to approve sugammadex, citing concerns about its possible association with allergic reactions and bleeding. The advisory panel scheduled for this week was supposed to discuss Merck's revised application, which included new clinical data showing a slight increase in the risk of allergic reactions but no increase the risk of bleeding.
The study was conducted in the United States, the Netherlands, the United Kingdom and Germany.
The sudden delay surprised analysts and clinicians alike.
"I'm surprised to hear about this last-minute issue," said Dr. Glenn Murphy, an anesthesiologist and director of clinical research at North Shore University Health System in Evanston, Illinois, who was an adviser to Merck on sugammadex. "I thought everything was moving along towards getting this drug approved."
Sugammadex is already approved in more than 50 countries, where it is sold under the brand name Bridion. It generated worldwide sales of $261 million in 2012.
Analysts on average forecast U.S. sales of sugammadex, if approved, to reach $663 million annually by 2018, according to Reuters data. It would compete with Valeant Pharmaceuticals International Inc's Prostigmin, known generically as neostigmine, and Tensilon, also known as edrophonium.
"Given the success it's had outside the United States and the clinical data I've seen, I'm optimistic," said Damien Conover, an analyst at Morningstar.
Muscle relaxants are typically used as part of the anesthesia process at the beginning of an operation to help doctors insert a breathing tube. They can also be used during surgery to prevent muscle movements that could complicate a procedure.
After surgery physicians use reversal agents to undo the effects of these muscle relaxants so that patients can breathe, eat and swallow on their own. Sugammadex is the first in a new class of drugs designed to reverse the effect of the muscle relaxants rocuronium and vecuronium.
Sugammadex's path toward approval has been far from smooth. The product was originally developed by Organon BioSciences, which was acquired by Schering-Plough in 2007 for $14.4 billion. Merck acquired the drug when it bought Schering-Plough for $41 billion in 2009.
Organon also developed Raplon, a muscle relaxant that was withdrawn from the U.S. market in 2001 after being associated with fatal episodes of airway constriction known as bronchospasms.
In March, the FDA said it would not complete its review of sugammadex until Merck provided more clinical data on allergic reactions, though Merck said at the time it had completed the necessary trials and that the FDA had accepted its resubmitted marketing application.
The delay is the latest in a number of setbacks for Merck, coming just two weeks after the FDA rejected the company's insomnia drug suvorexant, though it left the door open for the company to submit a lower-dose version for approval. In February Merck said it would delay its marketing application for odanacatib, an experimental osteoporosis drug, and in March it replaced its research chief.
Merck said it is "engaged in discussions with the FDA" to identify the steps necessary to enable the agency to complete its review of sugammadex, which the company believes offers significant advantages over its competitors, particularly in the speed with which it takes effect.
Patients taking sugammadex to reverse deep paralysis caused by rocuronium emerged, on average, in 2.2 minutes, according to pooled data from late-stage clinical trials conducted by Merck and submitted to the FDA. Patients taking neostigmine emerged in 19 minutes, while those taking a placebo emerged in 92.9 minutes.
In patients given sugammadex to reverse the effects of vecuronium, patients emerged in 3.8 minutes on average compared with 67.6 minutes for those taking neostigmine, the company said.
David Michelson, Merck's head of neuroscientific research, said that in a trial of 448 patients who received 16 milligrams of sugammadex per kilogram of body weight - an amount given only on an emergency basis - one patient experienced a clear anaphylactic reaction, characterized by a drop in blood pressure, hives, increased heart rate and difficulty breathing.
Two other patients had reactions that were not clearly anaphylactic but shared some symptoms, while seven or eight more had milder allergic reactions such as nausea and rash, he said.
In patients taking the normal dose used in routine surgeries - 4 milligrams per 1 kilogram of body weight - there were no clearly anaphylactic reactions and only one mild reaction, Michelson said, adding that in a trial of nearly 1,200 patients undergoing hip or knee surgery, those who were given sugammadex were no more likely than those who were not given it to have episodes of bleeding.
In 2012, nearly 5 million surgeries in the U.S. included the use of rocuronium and vecuronium. About 60 percent of those also involved the use of a reversal agent, according to IMS Health.
Merck's shares fell 0.6 percent to $48.23on the New York Stock Exchange.
(Additional reporting by Ransdell Pierson in New York; Editing by Carol Bishopric and Prudence Crowther)