Experimental Sleep Drug, Suvorexant, Raises FDA Concerns

The U.S. Food and Drug Administration (FDA) says that experimental insomnia drug, suvorexant, manufactured by Merck & Co. Inc., may be associated with dangerous side effects.

The experimental insomnia medication was found to be effective at helping patients sleep; however, suvorexant was found to have some significant side effects, such as daytime drowsiness and suicidal ideation, the agency’s advisory committee warned, according to CBS/The Associated Press (CBS/AP). The FDA released a review of suvorexant this week, in advance of today’s public meeting.

The agency said that Merck trials showed that the sleep aid is better at helping people fall asleep, and stay asleep, when compared to a placebo. Regulators said suvorexant’s efficacy was consistent when tested by Merck across different doses, according CBS/AP. But, patients taking higher doses of suvorexant experienced an eight-fold increase in daytime drowsiness; in some cases, this drowsiness interfered with their driving the next morning, said CBS/AP. In fact, those patients who took 20 milligrams and 40 milligrams of suvorexant were challenged when attempting to remain in their driving lanes when tested by Merck researchers. According to the agency, four women involved in the study had to cease their part of the test due to extreme sleepiness.

The drug was also associated with suicidal ideation. In the course of one year, eight cases of suicidal thinking or behavior were reported in patients taking suvorexant; no cases were reported in the placebo group, said MedPage Today The data were pooled from three phase III studies, according to FDA briefing documents released earlier this week in advance of today’s FDA’s Peripheral and Central Nervous System Drugs Advisory Committee meeting.

“These data, taken together, suggest to us that all doses studied (down to, and including, 10 mg) are effective for both endpoints,” Russell Katz, MD, director of the FDA’s neurologic products division, wrote. “There is little evidence to suggest that the higher doses are substantially superior to 10 to 15 mg, at least for sleep maintenance, and likely for sleep latency as well.”

The Committee will discuss suvorexant’s dosing and will vote on recommending approval on the drug’s various strengths. If approved, suvorexant would be the first in a new class of insomnia drugs called orexin receptor antagonists, which work by blocking brain chemicals that keep people awake, MedPage Today explained.

The study involved 1,022 patients in, for the most part, Europe, Japan, and North America; participants were given either a low or high dose of suvorexant or a placebo, according to MedPage Today.

Women and obese participants faced more challenges clearing suvorexant from their bloodstreams, which made them more susceptible to adverse events and more likely to need a lower dose, according to agency reviewers, MedPage Today wrote.

In response to the findings, Merck proposed the higher dose be recommended in suvorexant’s labeling—30 mg for seniors, 40 mg for younger patients—and proposed producing suvorexant in 40 mg, 30 mg, 20 mg, and 15 mg tablets.