Development

Incannex advances IHL-42X development strategy following positive Phase 2 obstructive sleep apnea results

Edited by Robert McTiernan··3 min read

Incannex Healthcare, a Melbourne and New York-based clinical-stage biopharmaceutical company, announced an updated clinical development strategy for IHL-42X following Phase 2 data from the completed RePOSA trial in patients with obstructive sleep apnea. The results carry weight because no oral pharmacotherapy is currently approved by the US FDA to treat the underlying airway obstruction in OSA, a condition managed almost entirely through devices such as continuous positive airway pressure machines, which are limited by poor patient adherence.

Trial specifics

The RePOSA Phase 2 trial evaluated IHL-42X, a fixed-dose oral combination of dronabinol and acetazolamide, at two dose strengths in patients with OSA. According to the company, 33.3% of patients in the low-dose group and 41.2% in the high-dose group achieved greater than 30% reduction in apnea-hypopnea index (AHI), the standard objective measure of OSA severity. Reductions exceeding 50% were observed in 13.9% and 14.7% of patients in the low- and high-dose groups, respectively. Maximum individual AHI reductions reached 83% at high dose and 79% at low dose. The company reported that 58% of participants described their condition as improved, and among those, approximately 90% characterized the benefit as meaningful to daily life. No serious adverse events were reported. The company also stated that REM sleep was preserved, which it described as a differentiator from existing sleep medications. The company did not disclose the total number of patients enrolled, the trial's ClinicalTrials.gov identifier, or detailed statistical methodology. Incannex has stated that the results were statistically significant across both objective physiological measures and patient-reported outcomes, though full data have not yet been published in a peer-reviewed journal.

Following these results and discussions with the US FDA, Incannex said it will conduct a Phase 2 crossover dose-optimization study called DReAMzz, evaluating multiple ratios of dronabinol and acetazolamide to identify a formulation that delivers consistent efficacy across both endpoint categories. The company said it has appointed a contract research organization and expects to begin dosing patients in the coming months. Data from DReAMzz are intended to inform a streamlined Phase 3 program, which Incannex said may be conducted under a single master protocol with parallel studies. IHL-42X holds US FDA Fast Track Designation, which provides more frequent regulatory interaction but does not guarantee approval.

Research context

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IHL-42X combines two mechanisms. Dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, is a partial agonist at CB1 and CB2 cannabinoid receptors and is thought to stabilize upper airway muscle tone during sleep. Acetazolamide inhibits carbonic anhydrase enzymes, producing mild metabolic acidosis that stimulates respiratory drive. The combination is designed to act on complementary pathways contributing to airway collapse and reduced ventilatory effort in OSA. Current obstructive sleep apnea treatment relies on CPAP as the standard of care, supplemented by oral appliances and, in select patients, hypoglossal nerve stimulation via the Inspire device. Pharmacological agents such as solriamfetol (Jazz Pharmaceuticals), a dopamine and norepinephrine reuptake inhibitor, are approved for residual excessive daytime sleepiness associated with OSA but do not address the underlying obstruction. No oral drug currently targets the disease mechanism itself.

Key competitors include:

  • Inspire Medical Systems' hypoglossal nerve stimulation device, an implantable neurostimulator with US FDA approval for moderate-to-severe OSA, currently in expanded-indication trials.
  • Jazz Pharmaceuticals' solriamfetol, approved for excessive daytime sleepiness in OSA and narcolepsy, with ongoing Phase 2 studies in broader OSA populations.
  • Takeda's TAK-925, an orexin 2 receptor agonist in Phase 2 for excessive sleepiness associated with OSA and narcolepsy.

None of these targets the same dual mechanism as IHL-42X, and none is an oral therapy directed at the underlying airway obstruction.

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