A sleeping pill that offers the snooze-inducing benefits of Ambien and Lunesta while avoiding next-day grogginess and disorientation has eluded drug heavyweights including GlaxoSmithKline (GSK) and Japan’s Takeda Pharmaceutical (TKPYY). Merck (MRK) thinks it may have found a solution.
The drugmaker is in final testing of an insomnia product, named suvorexant, that works differently from the market leaders. Rather than boosting the brain’s complex sleep system, suvorexant uses a more precise approach to block a tiny group of receptors that keep the body alert.
If approved by the Food and Drug Administration, the pill could generate $900 million annually for Merck, according to Barclays (BCS) analyst Tony Butler. “It’s not whether you put the patient to sleep, it’s how you feel the next day,” says Rafael Pelayo, a professor at the Stanford Center for Sleep Sciences and Medicine.
About 70 million American adults, or one-third, have trouble falling or staying asleep, according to the American Psychiatric Association. “That’s why I think the pharma industry and investors look at sleep as a good place to put their money,” Pelayo says.
History isn’t on Merck’s side. London-based Glaxo last year ended development of its most promising sleep drug, almorexant, during trials after agreeing to spend as much as 4 billion Swiss francs ($4.07 billion) to buy it from Actelion. The problem: Patients couldn’t tolerate its side effects, which remain undisclosed. Sanofi’s (SNY) bid to replace its own Ambien product, which faced generic competition for the first time in 2006, ended in 2009 when the Paris-based drugmaker failed to get U.S. approval for the treatment, called Ciltyri, after its risks were considered to outweigh its benefits.
Meanwhile, two recently regulatory-certified insomnia drugs have failed to take hold with consumers. Takeda’s Rozerem, approved in the U.S. in 2005, logged just $11.7 million in sales last year, while Somaxon Pharmaceuticals’ (SOMX) Silenor generated only $16.2 million. The newer therapies failed because they haven’t reduced side effects such as headaches or nausea, says Stanford’s Pelayo.
The failures have helped clear the field for Merck’s suvorexant, part of a potential new class of drugs known as orexin receptor antagonists. The medicines may provide the same or better effectiveness against insomnia with fewer side effects, says Thomas Roth, director of research at the Sleep Disorders and Research Center at Henry Ford Health System in Detroit who worked with Merck on the study and consults with other pharmaceutical companies. “The therapy of insomnia has changed from trying to augment the power of the sleep system to trying to inhibit the wake system,” says Roth.
Older sleep drugs including Ambien and Lunesta target billions of neuron receptors, affecting a wide range of body activities to achieve their goals. Orexin receptors targeted by the Merck drug are far fewer, with tens of thousands located in the brain’s hypothalamus. That makes for a more focused drug, says Darryle Schoepp, Merck’s head of neuroscience development. In a study sponsored by Merck, patients on suvorexant performed better at a driving test the next day, staying in their lane more than patients on eszopiclone, the generic name for Dainippon Sumitomo Pharma’s Lunesta. Merck’s clinical trial has lasted a year, longer than that of any other sleep drug, which the company says may mean it’s possible for patients to use the drug for longer than current therapies. Glaxo completed a 48-person trial of its own orexin drug in 2007, though it has yet to report data. Takeda is investigating orexin medicines as well, according to a scientific study describing the work. But Merck’s drug is the only one of the new class in the final of three stages of clinical trials usually required for regulatory approval. “There’s no second at this point,” says Roth.