Ian Parker reports at length on Suvorexant, an insomnia medication, and Merck’s efforts to get it FDA-approved:
The central nervous system is in an ever-adjusting balance between inhibition and excitation. Ambien, like alcohol or an anesthetic, triggers the brain’s main inhibitory system, which depends on binding between gaba—gamma-aminobutyric acid, a neurotransmitter—and gaba receptors on the surface of billions of neurons. gaba receptors can be found throughout the brain, and when they’re activated the brain slows. Ambien encourages the process by sticking to the receptors, holding open the door to the neurotransmitter.
Suvorexant, which Merck describes as “rationally designed”—rather than stumbled upon, like most drugs—influences a more precise set of neurotransmitters and receptors. Orexin neurotransmitters, first identified fifteen years ago, promote wakefulness. When suvorexant is in the brain, orexin is less likely to reach orexin receptors. Instead of promoting general, stupefying brain inactivity, suvorexant aims at standing in the way of a keep-awake signal. This difference may or may not come to mean a lot to insomniacs, but Merck’s marketing is likely to encourage the perception that suvorexant ends the dance by turning off the music, whereas a drug like Ambien knocks the dancer senseless.
But the FDA wants the drug’s recommended dosage to be lowered significantly:
The F.D.A.’s decision left Merck facing an unusual challenge. In the Phase II trial, this dose of suvorexant had helped to turn off the orexin system in the brains of insomniacs, and it had extended sleep, but its impact didn’t register with users. It worked, but who would notice? Still, suvorexant had a good story—the brain was being targeted in a genuinely innovative way—and pharmaceutical companies are very skilled at selling stories.
Merck has told investors that it intends to seek approval for the new doses next year. I recently asked John Renger how everyday insomniacs would respond to ten milligrams of suvorexant. He responded, “This is a great question.” After the approval process is finished, the marketing division of Merck—a company whose worldwide sales last year totalled forty-seven billion dollars—will conduct a different kind of public trial. The study will address this question: How successfully can a pharmaceutical giant—through advertising and sales visits to doctors’ offices—sell a drug at a dose that has been repeatedly described as ineffective by the scientists who developed it?
The Dish 