Pivotal data suggest clean safety profile, potency could set Idorsia's sleeping pill apart
Swiss biotech Idorsia, spun out of Actelion after J&J wrapped up its $30 billion takeover in 2017, is one step closer to the finish line with a positive late-stage study of its insomnia drug.
The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was being tested in 930 adult and elderly patients with insomnia. Both doses (25 and 50 mg) of the therapy improved sleep onset and sleep maintenance, as well as subjective total sleep time at the end of month 1 and month 3, the company said, without disclosing specifics.
In addition, daridorexant improved daytime performance, as measured by patients feeling less physically and mentally tired, less sleepy and more energetic during the day.
The drug’s side-effect profile was also largely benign, with more serious adverse events on the placebo arm. There were also no next-morning residual effects, rebound insomnia, or withdrawal symptoms upon discontinuation, and no suicide, suicidal ideation or self-injury observed.
H.C. Wainwright analyst Raghuram Selvaraju suggested its favorable safety profile pits daridorexant as a “best-in-class drug” with the potential for broad penetration versus earlier-generation orexin receptor modulators, such as Merck’s Belsomra and Eisai’s recently approved Dayvigo.
“While we designed daridorexant to have the optimal profile for a sleep medicine, I am none-the-less stunned by the results,” said chief Jean-Paul Clozel in a statement. “Once approved, by providing daridorexant to the millions of patients with insomnia, Idorsia will have a major impact on this medical, social, and economic problem. It has struck me particularly in these times of confinement that we are living through, that sleep problems are a major issue and require an extremely safe and effective drug that can be used by many.”
A separate pivotal trial testing 10 mg and 25 mg doses over three months is expected to read out in the third quarter.
The insomnia market is underserved, with multiple options that carry serious safety concerns such as sleepwalking and sleep-driving — the best-known examples include zolpidem (originally marketed as Ambien), eszopiclone (originally marketed as Lunesta) and zaleplon (formerly marketed as Sonata), as well as benzodiazepines such as diazepam, flurazepam and temazepam, Selvaraju said.
“From our vantage point, daridorexant appears much safer than all of these and could potentially be positioned as the safest-ever insomnia drug, if approved,” he said.
He estimated peak sales of nearly $1.3 billion in the United States and Europe by 2030.
Back in 2008, Idorsia parent Actelion inked a deal worth up to $3.25 billion with GSK for another DORA, almorexant. At first, almorexant was tagged with sky-high expectations in the region of $6 billion in annual sales, but by 2011, a pivotal study testing the drug was halted due to an undisclosed tolerability issue.
Merck, meanwhile, did get a DORA on to the market — Belsomra — albeit with a label that highlights the potential for abuse and day-after effects, which limited its uptake.
Orexins, also called hypocretins, are naturally produced by the hypothalamus. As some people with narcolepsy experience a loss of orexin-producing neurons, orexins are understood to play a role in wakefulness and arousal.