Suvorexant’s adverse effects, including sense of looming doom, failed to keep FDA up at night
According to the New Yorker magazine, in May of 2013 a team from the pharmaceutical company Merck “hoped to persuade [an FDA] committee of seventeen, composed largely of neurologists, that suvorexant was safe and effective” as a sleep medication.
The committee, which would also hear from FDA scientists, would deliver a recommendation to the agency. If approved, suvorexant—whose mechanism, inspired partly by research into narcoleptic dogs, is unlike anything on the market—would be launched within a year. “Some industry analysts had described it as a possible blockbuster, a term usually reserved for drugs with annual earnings of a billion dollars,” said the magazine. “Merck had not created a blockbuster since 2007, when it launched Januvia, a diabetes drug.”
“The Merck team was frustrated,” the New Yorker said. This was due to the FDA’s draft of a presentation to be delivered by an FDA neuroscientist who had reviewed thousands of pages of Merck data. Of particular concern were the side effects described in the scientist’s report.
In it, the magazine said, “he noted suicidal thoughts among trial participants, and the risk of next-day sleepiness,” and quoted from Merck’s patient notes: “Shortly after sleep onset, the patient had a dream that something dark approached her. The patient woke up several times and felt unable to move her arms and legs and unable to speak. Several hours later, she found herself standing at the window without knowing how she got there.” A woman of sixty-eight lay down to sleep “and had a feeling as if shocked, then felt paralyzed and heard vivid sounds of people coming up the stairs, with a sense of violent intent.” A middle-aged man had a “feeling of shadow falling over his body, hunted by enemies, hearing extremely loud screams.”
To say the least, an FDA presentation that “focuses on individual ‘adverse events’—and draws attention to patients feeling ‘hunted by enemies’—is discouraging to a drug’s sponsor,” as the New Yorker piece points out.
Suvorexant, which Merck describes as “rationally designed”—rather than stumbled upon, like most drugs—influences a more precise set of neurotransmitters and receptors. Ambien, one of America’s most popular pharmaceuticals, targets GABA (gamma-aminobutyric acid), the primary inhibitory neurotransmitter, which is present throughout the central nervous system.
Now available generically as zolpidem, Ambien is “the cheap drug that suvorexant had to take on, if not unseat, in order to succeed in the sleep-medication market,” said the New Yorker. “In addition, rising public worry about risks associated with taking Ambien—ranging from amnesiac devouring of Pop-Tarts to premature death—had reduced the FDA’s tolerance for side effects in sleep medications.”
Despite its harrowing adverse effects, and the fact that it was repeatedly found to be ineffective—even by Merck’s own scientists—the FDA approved suvorexant (branded as Belsomra) in August 2014, but at lower doses than those in Merck’s original application.