Idorsia adds insomnia to its pipeline successes

Daridorexant scores in the first of two phase III insomnia studies, but attention will fall on a secondary endpoint measuring daytime performance.

When Idorsia was created in the wake of Johnson & Johnson’s takeover of Actelion, and then licensed its lead to J&J, its fate looked to be sealed. But instead of also being taken over Idorsia has set about developing its own pipeline, and today reported a positive pivotal study hit with daridorexant, a separate lead asset.

Daridorexant, a dual orexin receptor antagonist in development for insomnia, looks to have aced all four primary endpoints in the first of its two phase III trials, at both doses tested. While the data have yet to be scrutinised in detail, what looks to be an absence of sleep-inducing drugs’ typical side effects could give Idorsia’s immunology/cardiology pipeline an added focus.

However, analysts will likely zero in on one key secondary endpoint, namely patients’ daytime performance. This was measured using IDSIQ, a patient-reported questionnaire developed by Idorsia and validated by the US FDA.

According to this metric daridorexant 50mg, but not 25mg, hit statistical significance versus placebo. This is important because Idorsia’s second pivotal trial tests 10mg and 25mg, so if this result is consistent the company might see no benefit on daytime performance in the second study.

Nevertheless, on an analyst call today executives said the trial that just read out marked the first time an insomnia product had improved performance during the day in addition to improving sleep quality at night.

Daridorexant enables patients to “sleep faster, sleep longer and function better the next day”, said Idorsia’s chief executive, Jean-Paul Clozel. Whether a single trial backing just one dose of a product is sufficient to make such a claim will remain a key focus as the markets await full data and readout of the second pivotal study, due later this year.

As for the primary endpoints, there seems little doubt about daridorexant’s efficacy. Both doses beat placebo in one and three-month sleep maintenance and sleep onset.

WASO = wake after sleep onset (measure of sleep maintenance); LPS = latency to persistent sleep (sleep onset); sTST = subjective total sleep time; IDSIQ = insomnia daytime symptoms and impacts questionnaire. Source: Idorsia presentation.

Perhaps even more importantly, adverse events looked balanced across the three cohorts; numerically there were more falls and fainting with placebo than active drug, and none of the adverse events listed were more prevalent with 50mg than with 25mg.

Safety is a vital consideration for insomnia drugs, because of their propensity to cause sleepiness during the day. Two other orexin receptor antagonists are approved – Merck & Co’s Belsomra and Eisai’s Dayvigo – but both carry warnings of daytime impairment and possible effects on driving performance.

With Idorsia trading up 16% today, clearly the hope is that daridorexant could revolutionise insomnia treatment; sellside forecasts see 2024 revenue of $190m at present, according to EvaluatePharma, so an upgrade looks likely should the full data retain their lustre.

Daridorexant’s development also owes much to persistence in R&D; when Mr Clozel was running Actelion that company had been developing an earlier version of the orexin approach, almorexant, but this project was pulled because of drug-drug interactions (Actelion re-awakens research on sleep medicine, July 7, 2016).

Today’s daridorexant data back the decision to press on. Three years after Mr Clozel got J&J to pay $30bn for Actelion and $230m for an Idorsia asset, the Midas touch has not deserted him.

Daridorexant's pivotal programme
Study Design Data
NCT03545191 25mg & 50mg vs placebo All primary endpoints met; secondary performance endpoint (IDSIQ) stat sig only for 50mg
NCT03575104 10mg & 25mg vs placebo Study ends Apr 2020

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