IHL-42X to Enter Phase 3 Trials for Obstructive Sleep Apnea Following Positive Phase 2 Data

Joel Latham

Newly announced findings from the phase 2 RePOSA trial (NCT06146101) showed that IHL-42X (Incannex), an investigational therapy for obstructive sleep apnea (OSA), led to clinically meaningful improvements in key end points, including both objective and subjective aspects of OSA. Based on these findings, preparations for an End-of-Phase 2 meeting with the FDA are underway, with the goal to optimize a phase 3 trial design and regulatory strategy.¹

RePOSA included 121 adult patients with moderate to severe OSA who were randomly assigned to either high- or low-dose IHL-42X, or placebo, for a 28-day treatment period. At the conclusion of that period, investigators observed statistically significant reductions in percent change of Apnoea-Hypopnea Index (AHI), the primary end point, in both the low- and high-dose IHL-42X groups relative to placebo (P <.05).

Overall, the greatest reductions in AHI reached up to 83% in the high-dose group and up to 79% in the low-dose group. In the low-dose group, 33.3% of patients achieved more than a 30% reduction in AHI, while 13.9% experienced reductions over 50%. Similarly, in the high-dose group, 41.2% saw reductions greater than 30%, and 14.7% exceeded the 50% threshold–highlighting a strong therapeutic response in a meaningful portion of patients.

"We are extremely pleased with the RePOSA trial results. The combination of statistically significant improvements across multiple endpoints and an outstanding safety profile positions IHL-42X as one of the most compelling drug candidates in the global race to bring a pharmaceutical treatment for OSA to market,” Joel Latham, chief executive officer and president of Incannex, said in a statement.¹ "The depth of response seen in a defined subset of patients further reinforces our belief in its clinical and commercial potential. These results are a clear signal of the strength of our development strategy and a critical step forward in building long-term shareholder value. We continue to facilitate commercial discussions and look forward to providing shareholders with an update in this regard soon."

IHL-42X is an oral fixed-dose combination of dronabinol (synthetic THC) and acetazolamide, developed for patients with OSA, including those unable or unwilling to use CPAP devices. The belief is that by targeting multiple pathophysiological mechanisms of OSA (i.e. ventilatory stability and upper airway dilator muscles), that IHL-42X may promote a greater reduction in OSA severity.

In RePOSA, those in the low-dose IHL-42X group demonstrated statistically significant improvement (P <.05) in Patient Global Impression of Change (PGI-C)-Sleep, as well as PGI-C Fatigue. Both dosed groups revealed statistically significant improvements in oxygen desaturation index, indicating better oxygenation during sleep.

IHL-42X-treated patients in both groups showed several clinically significant improvements in a number of patient-reported outcome measures, including the Functional Outcomes of Sleep Questionnaire-10, PROMIS Sleep-Related Impairment 8a, PROMISE Fatigue 7a, and Epworth Sleepiness Scale. In the high-dose arm, IHL-42X significantly improved polysomnography metrics, reducing wake after sleep onset by 29.8% and apnea-hypopnea index during supine sleep by 30.3%, indicating meaningful gains in objective sleep quality.

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Throughout the study, the investigational agent was considered well tolerated, with no serious adverse events (AEs) reported. Overall, all treatment-emergent AEs were infrequent, with the majority being mild or moderate in severity.

"These findings highlight the statistically significant treatment effects observed across multiple measures of disease severity and patient experience," Mark Bleackley, chief scientific officer at Incannex, said in a statement.¹ "Combined with an excellent safety and tolerability profile, the results provide strong validation of IHL-42X’s potential as an innovative and impactful therapy for obstructive sleep apnea."

Prior to RePOSA, the combination of dronabinol and acetazolamide was studied in a small-scale, double-blind, placebo-controlled, crossover trial, published in Sleep earlier this year. The trial featured 11 patients with OSA who received 1 week of IHL-42X at east of 3 doses and placebo, each separated by a 1-week washout.²

At the conclusion of the treatment period, results showed that IHL-42X led to greater reductions in AHI vs placebo (low, –19.7 [±27.1]; medium, –17.5 [±23.3]; high, –16.4 [±23.8]; vs placebo, –2.8 [±21.0] events/hour; all P <.05). In addition, the change in oxygen desaturation index was greater for the medium IHL-42X dose when compared with placebo (–15.4 [±19.0] vs placebo, –2.8 [±21.0] events/hour; P <.05), but not the low or high doses (low, –15.2 [±24.8]; high, –8.3 [±13.2] events/hour). In the trial, IHL-42X showed no impact on Epworth Sleepiness Scale or mood.

REFERENCES
1. Incannex Reports Positive Topline Results from RePOSA Phase 2 Trial of IHL-42X. News release. Incannex. July 30, 2025. Accessed July 31, 2025. https://www.globenewswire.com/news-release/2025/07/30/3124000/0/en/Incannex-Reports-Positive-Topline-Results-from-RePOSA-Phase-2-Trial-of-IHL-42X.html
2. Walsh J, Rankin T, Mehra S, et al. A randomized dose finding study of combination dronabinol and acetazolamide for the treatment of obstructive sleep apnea. SLEEP. 2025;48(4):zsae276. doi:10.1093/sleep/zsae276.