FDA raises concerns about experimental sleep aid suvorexant

WASHINGTON While an experimental insomnia drug from Merck was effective at helping patients sleep, it also had dangerous side effects including daytime drowsiness and suicidal thinking, a Food and Drug Administration (FDA) advisory committee warned.

The Food and Drug Administration on Monday released a review of the company's sleep aid, suvorexant, ahead of a public meeting on Wednesday. The pill works by temporarily blocking chemical messengers that keep people awake.

The FDA said company trials show suvorexant is better than placebo at helping people fall asleep and stay asleep. And regulators said the drug's effectiveness was consistent across several doses tested by Merck & Co. Inc.

But patients taking the higher doses of the drug showed an eight-fold increase in daytime drowsiness, which sometimes interfered with driving the next morning. Patients taking 20 milligrams and 40 milligrams of suvorexant had trouble staying in their driving lanes when tested by company researchers. FDA notes that four women actually had to stop the driving test due to excessive sleepiness.

The FDA review also notes that suvorexant was associated with increased risk of suicidal thinking. Over 12 months, there were eight cases of suicidal thinking or behavior reported among patients taking the drug, compared with no cases among patients given placebo.

Merck has proposed a starting dose of 15 milligrams for seniors and 20 milligrams for non-seniors. Doctors would gradually raise these doses to 30 milligrams and 40 milligrams, respectively, or until the patient's insomnia has been successfully treated.

On Wednesday the FDA will ask a panel of outside experts to vote on questions of the drug's safety and effectiveness. The agency appears to favor eliminating most of the higher doses of the drug tested by Merck.

The FDA says Merck data suggest that a 10 milligram dose may be safer, while still being effective.

"Indeed, if a dosage strength lower than 15 milligrams is unavailable, we would need to consider if the drug could be marketed safely at all, if we believe that a substantial proportion of the indicated population needs a lower dose," the agency states in its review.

The agency plans to ask its advisers whether there is enough data to support a 10 milligram dose, according to draft questions posted online.

ISI Group analyst Mark Schoenebaum called the FDA's review "tough."

"The high dose is deemed unsafe, and the FDA wonders if there is enough data at the safer low dose to draw firm safety conclusions," Schoenebaum said in a note to investors. He says it could take Merck 18 months to resubmit its drug, if FDA requires another study of low-dose suvorexant. The potential impact on Merck's revenue is relatively small, since the drug is only expected to generate peak sales of $650 million by 2018.

The FDA has also been monitoring other sleep drugs that are currently on the market.

In January, the FDA asked drugmakers of Ambien and similar sleeping pills to lower the dosage of their drugs, based on studies suggesting an increased risk for drowsiness-related injuries. The agency cited research showing that the drugs remain in the bloodstream at levels high enough to interfere with driving.

Regulators mandated that the dose of the medications be halved for women, who process the drug more slowly for unknown reasons. Doses will be lowered from 10 milligrams to 5 milligrams for regular products, and 12.5 milligrams to 6.25 milligrams for extended-release formulations.

The number of emergency room visits caused by zolpidem -- the active ingredient in sleeping aids like Ambien, Ambien CR, Eldular and Zolpimist -- rose 220 percent from 2005 to 2010, Substance Abuse and Mental Health Services Administration (SAMHSA) reported in May.

"Although short-term sleeping medications can help patients, it is exceedingly important that they be carefully used and monitored," SAMHSA Administrator Pamela S. Hyde said in a press release at the time. "Physicians and patients need to be aware of the potential adverse reactions associated with any medication, and work closely together to prevent or quickly address any problems that may arise."

In midday trading, shares of Whitehouse Station, N.J.-based Merck slipped 52 cents to $45.48.