Minerva Neurosciences’ seltorexant helped patients fall asleep more quickly and stay asleep for longer, beating placebo and Sanofi’s insomnia med Ambien in a phase 2b study. The company’s stock leapt as high as 86% Monday morning to $7.85 a share before settling down around the $6.00 mark.
The Waltham, Massachusetts-based biotech is developing seltorexant with Janssen as an add-on treatment for major depressive disorder and insomnia disorder. While Ambien (zolpidem) activates the GABAA receptor to treat insomnia, seltorexant works by blocking the orexin-2 receptor. The orexin system promotes wakefulness and is believed to have a hand in excessive arousal in patients with insomnia as well as some patients with mood disorders.
“Unlike existing therapies, seltorexant is designed to mimic the natural sleep process by inhibiting the brain mechanisms that promote excessive wakefulness rather than by sedating patients through the activation of the neurotransmitters that promote sleep,” said Minerva CEO Remy Luthringer, Ph.D., in a statement.
The phase 2b study enrolled 365 patients, randomizing them into five groups. Three of the groups received a 5 mg, 10 mg or 20 mg dose of seltorexant, with the remaining groups receiving either placebo or Ambien. The investigators measured the patients’ responses on the first night and the thirteenth night of treatment using polysomnography, a test that measures brain waves, blood oxygen levels, heart rate, breathing and eye and leg movements.
On night one, patients on placebo saw a 15-minute improvement in latency to persistent sleep (LPS), meaning they fell asleep in 15 minutes less time than baseline. All three dose levels of seltorexant outperformed placebo, meeting the study’s primary endpoint. The 20 mg dose worked best, with a 37-minute improvement over placebo, while the 10 mg and 5 mg doses logged 32-minute and 16-minute boosts, respectively. On night 13, these figures got closer together, but there was “a significant separation from placebo of the 10 mg and 20 mg dose groups,” Minerva said in the statement.
To gauge sleep duration, the study used WASO-6, which records periods of wakefulness after the patient has fallen asleep, over the course of six hours.
“WASO-6 was selected as the key secondary endpoint since seltorexant has a short half-life, and in previous studies some subjects awoke after 6-7 hours and did not feel the need for additional sleep,” the company said in the statement. “Moreover, WASO-6 is often considered to be a clinically relevant measure in sleep trials, since working adults commonly do not elect to remain in bed asleep for an entire 8-hour period.”
All three doses of seltorexant beat placebo at improving WASO-6, with the 10 mg and 20 mg doses coming out tops. They both posted an improvement of 28.6 minutes over placebo on night one and a 16-minute and 22-minute boost on night 13, respectively.
As for how Minerva’s drug fared over Ambien, the 20 mg dose did the best, helping patients fall asleep 12 minutes faster than placebo and cutting down on wakeful periods by 12 minutes on night 13. The study used immediate-release Ambien, which bested placebo for both sleep onset and duration on night one, but not on night 13, “demonstrating a known decrease of effect of zolpidem over time,” Minerva said.
David Kupfer, M.D., distinguished professor emeritus of psychiatry at the University of Pittsburgh School of Medicine and board member of Minerva, said in the statement: “Based on these results and those from the recent MDD2001 study, observations of seltorexant include a clinically meaningful improvement in symptoms of depression in patients not responding adequately to first line therapies (SSRIs and SNRIs) and a clinically meaningful effect on insomnia in a wide age range of patients.
“The demonstration of a significant benefit across a broad spectrum of patients who suffer with depression and/or insomnia and who have not responded adequately to existing therapies points to a differentiated clinical profile and a new way to address an underserved patient population” Kupfer said.
On a conference call discussing the data, Minerva "suggested it could move all three doses forward into Phase III where it has optionality to evaluate the 5 mg in elderly or adolescent patients," Jefferies analysts wrote in a note. "Furthermore, the Phase III studies will likely evaluate patients out to month 3 (vs night 13 in the Phase Ib) for efficacy. One of the key experts on the call suggested efficacy tends to diminish with most insomnia drugs in the first 1-2 weeks, and therefore night 13 appears to be a strong reference of what one can expect at month 3 in a Phase III trial."