Phase 2 trials of Idorsia’s insomnia candidate ACT-541468 have met their primary endpoints. The top-line data link the dual orexin receptor antagonist (DORA) to significant decreases in the time subjects were awake in the night, sparking a rise in the Actelion spinout’s stock price and talk of partnering up to enter phase 3.
Investigators enrolled 360 adults in the larger of the two phase 2 trials and randomized them to receive either one of three doses of ACT-541468, placebo or zolpidem, a drug better known by the brand name Ambien. The trial dosed subjects for four weeks but was primarily interested in the effect of ACT-541468 on wake after sleep onset (WASO) in the two days after starting treatment.
Idorsia said the trial identified a significant, dose-dependent decrease in WASO. The trial also hit a secondary endpoint that assessed how long it took participants to get to sleep, a measure known as latency to persistent sleep (LPS).
A smaller trial in patients aged 65 years and older also linked ACT-541468 to significant declines in WASO and LPS.
The top-line data triggered a 9% rise in Idorsia’s CHF 2 billion ($2 billion) market cap as investors assessed the chances of ACT-541468 becoming a blockbuster. But people working at and investing in Idorsia don’t have to look far for an example of how a promising DORA can falter after showing promise in a mid-phase trial.
Idorsia’s parent company Actelion landed a deal worth up to $3.25 billion with GlaxoSmithKline for another DORA, almorexant, in 2008. Almorexant was spoken of as a $6 billion-a-year drug. But the wheels came off the program in 2011 when Actelion and GSK halted a phase 3 trial in response to an undisclosed tolerability issue.
Merck did succeed in bringing a DORA—Belsomra—to market but has failed to turn it into a major product. Hindered by a label that warns of the potential for abuse and day-after effects, Belsomra is yet to get anywhere near the sort of sales figures once foreseen for almorexant.
It is unclear from the scant phase 2 results shared by Idorsia whether ACT-541468 can fare better than other DORAs. Idorsia is yet to share data showing how ACT-541468 performed against the active comparator or information on its safety beyond that it was generally well tolerated. These details will dictate how likely ACT-541468 is to outperform the competition in terms of how quickly it gets people to sleep, how long they stay asleep and how little it impairs them the next day.
Idorsia plans to share more data at upcoming scientific congresses. But whatever management has seen is compelling enough for it to talk up advancing the program into phase 3. Some people think Idorsia will strike a deal before taking the next step.
“We expect a partner is likely preferred to co-fund these costly trials,” Jefferies analyst Peter Welford wrote in a note to investors.
Idorsia is partnered with Johnson & Johnson on hypertension drug aprocitentan, but ACT-541468 is unattached.