* FDA panel says suvorexant safe, effective at lower doses
* Merck drug is first in new class of sedatives
By Toni Clarke
WASHINGTON, May 22 Merck & Co's
experimental insomnia drug moved a step closer to U.S. approval
on Wednesday after a panel of medical experts said it is
effective and safe at lower doses.
The advisory panel was convened to help the U.S. Food and
Drug Administration decide whether to approve the drug,
suvorexant, which would be the first in a new class of sedatives
that block chemicals in the brain called orexins that help keep
people awake. The drugs are designed to help people fall asleep
and stay asleep.
On Monday, the FDA's internal reviewers published a report
expressing concern about suvorexant's potential to cause
next-day sleepiness and impaired driving. They asked the
committee to consider whether patients should be started at a
lower dose than that recommended by Merck.
Merck proposed that elderly patients start by taking 15
milligrams of the drug and increase that to 30 if necessary. The
company recommended non-elderly adults start on 20 milligrams
and increase to 40 milligrams if needed.
On Wednesday, the FDA reiterated its opinion that there was
little evidence in Merck's data to show that the higher dose was
more effective than the lower dose, and considerable evidence to
show it was less safe.
The FDA's reviewers pointed to an increase in the risk -
especially at the higher doses - of suicidal thoughts and
behaviors, impaired driving, and severe sleep disturbances.
Speaking for the FDA, Dr. Ronald Farkas noted cases in which
patients had reported sleep paralysis and terrifying
hallucinations. He also expressed the agency's concern about the
drug's impact on driving.
"What we are trying to prevent is criminal prosecution of
patients taking their drug as prescribed," he said.
The FDA's views were echoed by those of several patient
"Like its predecessors, suvorexant's marginal benefit in
extending overnight sleep time by a few minutes is achieved at
the expense of prolonged, next-day drowsiness, with potentially
fatal consequences," said Dr. Sammy Almashat, a researcher with
Public Citizen's Health Research Group who noted that suvorexant
stays in the body longer than all but one other sleep drug.
Still, the panel voted 13 to 3, with one abstention, that
the drug could be used safely at the 15 and 20 milligram doses.
It voted 8-7, with two abstentions, that the drug is not safe at
30 and 40 milligrams.
Merck celebrated the vote, saying in a statement that it was
"excited about the potential of suvorexant as a new and
different approach to treating insomnia."
The FDA is not bound to follow the advice of its advisory
panels but typically does so.
The FDA had asked the panel to consider whether patients
should start with a 10 milligram dose, saying data from a
smaller trial showed that amount might work for some people.
Merck disputed that, saying 10 milligrams would not be
The FDA also asked the panel if Merck should conduct an
additional trial to further evaluate a 10 milligram dose. The
panel voted against that. Some agreed that 10 milligrams would
not be effective. Others agreed in principal with a lower
starting dose, but most said a new trial would not add
meaningfully to the information already in hand.
"When you have something new you don't know everything you
would like to know," said Dr. Christian Guilleminault, a
professor at Stanford University School of Medicine. However, he
added: "I'm not sure that doing another study is going to bring
us much more."
The FDA's concerns come amid a broader review of the safety
of sleeping pills following hundreds of reports of driving
accidents involving people taking zolpidem, the active
ingredient in Sanofi SA's Ambien.
About 60 million prescriptions for these drugs were written
in the United States in 2011, according to healthcare research
firm I.M.S. Of those, roughly 40 million contained zolpidem.
In January, the FDA told drugmakers they should lower the
recommended dose of zolpidem in women to 5 milligrams from 10
for immediate-release products including Ambien, Edluar and
Zolpimist. The agency said doses for extended-release products
should also be cut in half.
Dr. Jason Todd, a panel member and staff neurologist at
NorthEast Neurology in Concord, North Carolina, said patients
are adjusting to the lower dosing recommendations for Ambien.
"Before the recent changes I almost never saw a patient who
would take 5 milligrams and stay with it," he said. "Now that 5
milligrams is recommended people are OK with 5 milligrams."
The panel's ultimate recommendation surprised some analysts
who had expected, based on the FDA's review, that the meeting
would be more contentious.
"Based on the overall discussion today and the voting of the
panel, we believe that the probability of FDA approval for
suvorexant has gone up meaningfully," Mark Schoenebaum, an
analyst at ISI Group, said in a research note.
Having said that, he said: "We admit that predicting a final
FDA decision is difficult."