Insomnia Drug Dosage Too High for Approval, FDA Says


July 01, 2013

Merck announced today that the US Food and Drug Administration (FDA) has informed it that the agency will not approve its new first-in-class insomnia drug called suvorexant until it is available — for safety's sake — in a starting dose of 10 mg for most patients.

Suvorexant blocks the action of neurotransmitters called orexins that regulate wakefulness and sleep.

Merck stated in a news release that it had learned of the FDA's negative decision on its insomnia drug in a complete response letter from the agency. The letter, as described by Merck, reflects the concerns over patient safety that were raised by the agency's Peripheral and Central Nervous System Drugs Advisory Committee in May when it recommended suvorexant for approval at higher doses.

The committee decided that the proposed doses of 15 and 30 mg for elderly patients and 20 and 40 mg for nonelderly patients were effective for both sleep onset and sleep maintenance. An overwhelming majority also agreed that the starting doses of 15 and 20 mg for elderly and nonelderly patients, respectively, were safe. However, the committee narrowly disagreed in a 7 to 8 vote that the safety of the upper-limit doses of 30 and 40 mg was acceptable, given a significant jump in next-day somnolence at those levels.

According to Merck, the FDA advised the company in its CRL that

  • the efficacy of suvorexant has been established at doses of 10 to 40 mg in elderly and nonelderly adult patients;

  • safety data do not support approval of doses at 30 and 40 mg;

  • when the recommended starting dose of 10 mg is well tolerated but not effective, clinicians could prescribe doses of 15 and 20 mg; and

  • the starting dose should drop down to 5 mg for patients who are also taking moderate CYP3A4 inhibitors.

Roger Perlmutter, MD, PhD, president of Merck Research Laboratories, said in the company news release that Merck expects "to work expeditiously with the FDA to make suvorexant available as the new treatment option for patients from insomnia."

Neither Merck nor the FDA would make a copy of the complete response letter available to Medscape Medical News.


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