If Merck’s new pill is as safe and effective as the FDA advisers are saying, physicians could prescribe it for people who simply can’t tolerate standard drugs.
A separate committee will meet Wednesday to discuss whether to recommend the use of the drug as a treatment for narcolepsy, a disorder that causes people to drift wildly and lose their sleep.
The FDA advisory panel convened on Tuesday — one day before the scheduled final vote on whether to approve the drug for that use — recommended approval for “adverse cardiovascular effects,” including an increased risk of stroke, heart attack and heart failure, possibly related to prolonged dosing.
Still, researchers with Merck’s medicinemaking division, led by chief medical officer of neuroscience Dr. Karen Midthun, say the drug is safe and provides fewer side effects than other similar products. It was previously known as tezepelumab, but Merck removed that name from the drug in September because of patient confusion over the previous trademark.
Doctors in other countries have not yet approved the drug for use as a prescription sleep aid.
Researchers found that its effectiveness remained strong, especially in people with narcolepsy who have become totally unresponsive to anything that would disrupt their sleep.
There were no deaths in patients taking the drug over several months, according to studies presented at the meeting in Washington. These included some people with an inherited form of narcolepsy, where its effectiveness is somewhat more variable.
“This drug is safe and well tolerated,” Midthun said in an interview Monday. The company conducted an extensive safety trial in adults with narcolepsy and “really studied this drug very closely.”
While the new drug has been shown to be safe, study chair Dr. Sibdabat Shah-Khan, an associate professor of neurology at Duke University Medical Center, said its ability to effectively treat narcolepsy patients remains limited.
She said that the study “showed that, on average, we have a 30% reduction in the occurrence of significant (sleep) disturbance with narcolepsy related to both drugs (pharmacotherapy and those with [sleep] apnea”) but … can only report an overall reduction of … 4% [of these] patients with a ‘reasonable certainty’ of magnitude.”
Midthun defended that fact, saying the study only includes patients who had failed to respond to at least one treatment. “The total treated population was only 30 people and each patient really needed to have failed on the first and second treatments to be treated with this combination of therapies,” she said. “This is a very complex disorder … you need to have multiple doses on patients to get a response.”
“This medicine works best in patients who have failed on a minimum of four prior doses,” Shah-Khan said. “It does work in some patients who do not have very severe sleep complaints.”
But she also raised concerns about the side effects, including the development of arterial stiffness in 40% of patients, and the increased risk of stroke, heart attack and heart failure that were reported. She pointed out that in seven patients treated for more than five years, there were 10 fatal events.
An agency spokeswoman said, “It is difficult to predict whether an expanded approval will provide additional benefit for patients in the setting of chronic insomnia.”
Dr. Robert Altschuler, who said he is not affiliated with any of the companies involved, said the small number of patients and long time exposure are significant hurdles to ensuring the success of an application like this. “It’s very tricky to get through this process,” he said.