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The approval of suvorexant, a novel insomnia drug, has been delayed because of issues related to the recommended doses of the drug, according to the manufacturer, Merck Research Laboratories.
The Food and Drug Administration has issued a complete response letter stating that the efficacy of doses from 10 mg to 40 mg have been established in elderly and nonelderly adults, but that the safety data do not support the approval of the 30-mg and 40-mg doses, the company said in a statement issued July 1.
In the letter, the FDA also advised Merck that 10 mg "should be the starting dose for most patients, and must be available before suvorexant can be approved," the Merck statement said. In addition, the letter states that that the 15-mg and 20-mg doses "would be appropriate" for people "in whom the 10-mg dose is well tolerated but not effective," and that a 5-mg dose would be necessary for people taking concomitant moderate CYP3A4 inhibitors.
The company had filed for approval of suvorexant, an orexin receptor antagonist, at doses of 20 mg (starting dose) up to 40 mg taken at bedtime for adults younger than 65 years, and 15 mg (starting dose) up to 30 mg for people aged 65 years and older. The company has data on the 10-mg dose, but did not file for approval of that dose.
However, at an FDA advisory panel meeting in May 2013, FDA reviewers concluded that the drug was effective, but were concerned about the potential serious side effects associated with the higher doses. Most of the panelists agreed that the drug was effective and that the starting doses were acceptably safe, but were divided on the safety of the higher doses.
The Merck statement says that an initial review of the letter indicates that clinical studies of the 10 mg dose would not be necessary, but manufacturing studies of the 10-mg dosage form would be needed. "We will evaluate the requests outlined in the complete response letter, and expect thereafter to work expeditiously with the FDA to make suvorexant available as a new treatment option," Dr. Roger M. Perlmutter, president of Merck, said in the statement.
The FDA does not announce when they send a company a complete response letter, which is issued for a drug when there are outstanding issues that need to be resolved before approval, but manufacturers can make these announcements.
Suvorexant blocks the binding of orexin A and B neuropeptides to orexin receptors, presumably inhibiting activation of neurons to the arousal system; if approved, it would be the first drug in this class to be approved.