By Toni Clarke
WASHINGTON, May 22 (Reuters) - 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 advocacy groups.
"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 effective.
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."
Also on HuffPost:
Start A Worry Journal
Before you get into bed, spend 10 minutes or so writing down what's really troubling you in a journal or on a piece of paper -- anything from work and family concerns to some issue or question that's really bugging you, Ojile says. "The reality is that writing it down in a worry journal isn't going to solve the problem," he says. But what it can do is give you a place to put down your thoughts and let them go until tomorrow.
Take A Bath
The benefits here are twofold. First, water tends to be soothing psychologically, Ojile says, which can help ease built-up stress from the day. But it can also benefit our sleep: The act of cooling the body, like that which happens when you get out of a warm tub, makes us feel tired. Don't want the fuss of taking a bath? Sipping a cup of warm, non-caffeinated green tea can trigger that same cooling response in the body, Ojile explains.
Say A Prayer (Or Meditate!)
If your mom told you to say your prayers before bed, she was on to something. No matter what you believe in, the act itself can help quiet your brain. "In order to pray or to meditate in a very effective way, you've got to let go of those things in life that are the same ones that keep you from sleeping," Ojile says. Both prayer and <a href="http://www.huffingtonpost.com/2011/07/15/7-fascinating-facts-about_n_899482.html#s309243&title=It_Makes_Your">meditation</a> can quiet the brain, which will ultimately keep you from tossing and turning in bed. And the act of repetition, like saying the rosary prayers in order, for instance, seems to be especially powerful, he adds.
Take A Walk
While some might find that strenuous exercise too close to bedtime only makes sleep more elusive, taking a leisurely walk a couple of hours before turning in can actually help. "An evening walk is a really helpful to help get rid of some of those stresses and strains from the day," Ojile says. "You always feel better after a walk."
Relax Your Muscles
One old-fashioned technique that can trigger sleep is called progressive muscle relaxation, which Ojile describes as almost a form of meditation and yoga. Here's how it works: Start down at your feet and work your way up the body, focusing on relaxing each part, one at a time. When you get to your core, take some deep breaths. "As you get to the deep breathing, you're by nature going to be ready for sleep," he says. "You're naturally feeling more calm and relaxed."
Spending some time cuddling with a partner before bed stimulates the kind of emotions that are, by nature, calming, Ojile explains. And that means better sleep. Having sex can also help (we bet you won't say no to that assignment). "It may prevent sleep immediately," he says, "but ultimately it promotes sleep and relaxation.