Second PhIII study for Idorsia's sleep drug returns positive results, but also raises new questions
Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.
The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.
Idorsia also tested 10 mg doses of daridorexant in the study and found positive response across all four efficacy measures, but all fell short of being statistically significant.
The new study measured daridorexant’s effects in 924 adult and elderly patients. Side effects from the tests remained low, as with the first study, with serious instances remaining balanced across dosage amounts and placebos, according to the biotech.
Results from the two studies regarding the 25 mg doses and placebos will now be pooled, and some analysts expect this will offer a promising profile to take to regulators. Questions will likely remain, however, given the caution that regulators usually take when approving insomnia treatments.
Peter Welford at Jefferies sees the poor results for the low dose as a good thing, as it removes any temptation the FDA may have to forgo the high dose and go with the less threatening lower dose — as they did with Merck. But its success is still no sure thing.
Importantly the lower 10mg dose showed smaller non-significant benefits, removing the risk regulators endorse a suboptimal dose to err on the side of caution, in our view. Commercial uncertainties remain.
Insomnia drugs generally are slow to become available and are difficult to produce. The drugs are also heavily regulated, as the FDA demonstrated when it imposed black box warnings last year on a slew of more commonly-known drugs like Lunesta, Ambien and Sonata.
Where DORAs differ from traditional insomnia drugs is in the inhibition of orexin signaling. Orexins, discovered in 1998, are hormones produced by the hypothalamus that regulate sleep, arousal and appetite.
Only two DORAs have hit the market in the US, but they also faced uphill climbs. Merck’s Belsomra (chemically known as suvorexant), released in 2014, required warning labels regarding next-day residual effects and abuse potential, among other safety risks.
Additionally, Eisai’s DORA Dayvigo (lemborexant) scored an FDA approval in December and launched last month but also needed similar warnings.
Idorsia spun off of Swiss pharma company Actelion after a $30 billion acquisition by Johnson & Johnson in early 2017. Idorsia had been Actelion’s old research and development department and is headed up by Actelion’s founder and CEO, Jean-Paul Clozel. Daridorexant is one of four developmental drugs currently in Idorsia’s pipeline that has reached the Phase III stage.