By Toni Clarke
WASHINGTON, July 16 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
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
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
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
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
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
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