TRENTON, N.J. - Drugmaker Merck & Co. said Monday that federal regulators have ruled they won't approve high doses of its experimental insomnia medication due to concerns about patient safety. However, the Food and Drug Administration indicated it would approve lower doses of the drug, suvorexant, after Merck does some new studies.
The agency's response likely will push back approval of suvorexant by at least several months.
"We're in ongoing discussions with the FDA" to determine exactly what studies are needed to develop "a clear pathway forward," Merck spokesman Steve Cragle said in an interview.
Merck had applied for permission to sell the sleeping pill in doses of 15, 20, 30 and 40 milligrams.
FDA staff and a panel of outside experts reviewed detailed data on patient testing by Merck at those doses. While both groups of experts determined suvorexant pills were effective at each dose, there were significant safety concerns with the 30- and 40-milligram doses.
Those included daytime drowsiness, trouble staying alert while driving and suicidal thinking. Those problems, hallucinations and traffic accidents all have been linked to other prescription sleep medicines, although Merck had been telling investors that suvorexant would cause less next-morning grogginess.
Roughly a third of adults have trouble falling or staying asleep and many are unsatisfied with existing insomnia medicines. Merck's drug would be the first in a new class of sleep medicines that work by blocking chemical messengers in the brain that help keep people awake.
The FDA notified Merck "very recently" that it wants 10 milligrams to be the starting suvorexant dose for most patients and also wants a 5-milligram dose available, Cragle said. The agency indicated the 15- and 20-milligram doses would be appropriate for patients who didn't get enough help from the 10-milligram dose and did not have serious side effects with it.
Cragle said that Merck, based in Whitehouse Station, N.J., has data showing the 10-milligram dose, but not the 5-milligram dose, is effective and safe.
That means patient studies may have to be done on the 5-milligram dose, and at the least, Merck will have to do manufacturing studies on the 10-milligram dose.
Merck will have to repeatedly produce batches at that dose to show it can consistently produce pills meeting strict specifications. That includes proving that the pills have the correct level of the active ingredient, dissolve properly and remain stable over time. Such studies are required before a company can begin selling any dosage of a new prescription drug.
"We can't put any timeframe on that," Cragle said.
Meanwhile, the FDA said it wants Merck to provide the 5-milligram dose for use in patients also taking medicines in a group called CYP3A4 inhibitors. Those drugs include nonsedating antihistamines and infection-fighting drugs from antifungal medications and antibiotics to HIV medications.
CYP3A4 inhibitors block an enzyme involved in breaking down many medications so they can be eliminated from the body. When that enzyme is slowed or shut down, levels of other drugs a patient is taking can build up too high in the bloodstream, causing dangerous interactions and side effects.