Fretting over the potential for serious side effects, the FDA has batted aside Merck's ($MRK) application to sell the new insomnia drug suvorexant, demanding that the pharma giant substitute a significantly weaker dose than the company had wanted to sell.
Merck says that the FDA rejected the 30 mg and 40 mg doses for suvorexant but believes that the 10 mg dose is the right starting point for most patients, with an option to bump that to 15 mg or 20 mg if the starting dose is not effective. And a 5 mg dose is being recommended for anyone also taking CYP3A4 inhibitors.
Based on the complete response letter, Merck R&D chief Roger Perlmutter concluded that the company shouldn't have to do another clinical study on the 10 mg dose, but will need to do some additional manufacturing work. Perlmutter says he plans to discuss whether a new study on the 5 mg dose is necessary ahead of any approval.
Merck pushed hard to avoid this scenario. The efficacy data on suvorexant is strongest at the highest doses and Merck officials bluntly told the FDA and its experts that they did not believe that a 10 mg dose would work. But in an internal FDA review and in discussions with the experts, agency staffers detailed serious concerns about the drug's safety and Merck lost a close panel vote on the high doses. Of particular concern for the FDA were the data demonstrating patients weren't really able to tell when they were alert enough to drive. The low dose wasn't tested in Phase III.
The FDA's decision won't improve the peak sales estimates that have been circulating. Most analysts think it's unlikely that suvorexant, which will eventually make its way into a shrinking market dominated by generics, will ever be the blockbuster that Merck had hoped for.
"We view the vote today as a positive (particularly after the tough briefing documents)," wrote ISI analyst Mark Schoenebaum minutes after the panel vote. "We believe consensus expectations entering the panel today were low. MRK thinks insomnia is a multi-billion dollar opportunity. We currently carry only ~$700M of risk adjusted peak sales and consensus currently estimates only ~$650M peak sales in 2018 (last year for which we have consensus sales)."
"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 for patients suffering from insomnia," said Perlmutter in a statement.
- here's the press release