FDA reviewers question safety of Merck's suvorexant

FDA reviewers said insomnia candidate suvorexant from Merck & Co. Inc. (NYSE:MRK) is effective at promoting sleep, but questioned the product's safety profile as well as the pharma's proposed dosing levels. In briefing documents released ahead of Wednesday's Pulmonary-Allergy Drugs Advisory Committee meeting to discuss an NDA for the dual orexin receptor antagonist, the reviewers said suvorexant doses that are lower than those proposed by Merck may offer similar efficacy and better safety. The reviewers noted that fewer patients received the lower doses in clinical trials.

The reviewers also outlined their suvorexant safety concerns, including daytime somnolence, narcolepsy-like syndrome and suicidal ideation. The lowest dose of suvorexant for which Merck is seeking approval is 15 mg, but the reviewers note that, "if a dosage strength lower than 15 mg 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." FDA is asking the committee to discuss whether a 10 mg dose would be an "appropriate recommendation as a starting dose." The questions also note that FDA believes the 15 mg dose "results in excessive suvorexant exposure" in some populations, including obese women and patients taking metabolic inhibitors. ...