The biopharmaceutical company will initiate a phase 2 dose-optimization study for its oral OSA therapy before advancing to a streamlined phase 3 program.

Key takeaways:

Incannex Healthcare is advancing IHL-42X, an oral combination therapy for obstructive sleep apnea, following positive phase 2 outcomes and FDA Fast Track Designation.
A new phase 2 crossover study, DReAMzz, will evaluate different ratios of dronabinol and acetazolamide to optimize the drug’s efficacy and safety profile.
Results from the dose-optimization study are expected to support a streamlined phase 3 clinical program, potentially shortening the timeline to registration.

Incannex Healthcare Inc has announced an updated clinical development strategy for IHL-42X, its lead oral drug candidate for the treatment of obstructive sleep apnea (OSA), following statistically significant outcomes in its completed phase 2 program.

The drug, an oral fixed-dose combination of dronabinol and acetazolamide, has been granted Fast Track Designation by the US Food and Drug Administration (FDA), which enables more frequent interaction with the agency as the program advances. The updated development strategy includes a phase 2 crossover dose-optimization study, dubbed DReAMzz, followed by a streamlined phase 3 clinical program.

“Following the strong, statistically significant outcomes from our phase 2 RePOSA trial, we believe IHL-42X is emerging as one of the most promising oral therapies in development for obstructive sleep apnea,” says Joel Latham, president and CEO of Incannex Healthcare, in a release. “The optimization study we are initiating is designed to further refine the drug’s efficacy while strengthening the clinical package ahead of phase 3. We believe the optimized study design provides a pathway that could accelerate development timelines, potentially shorten time to registration if successful, and allow us to progress efficiently through the end of phase 3 development.”

Data from the completed RePOSA Phase 2 trial demonstrated that IHL-42X achieved statistically significant and clinically meaningful improvements across both objective physiological measures and patient-reported outcomes. The study showed efficacy across both dose strengths, with differentiated performance observed between objective and subjective endpoints.

Following a review of the RePOSA data and discussions with the FDA, Incannex elected to conduct the phase 2 crossover study to evaluate alternative ratios of the two active pharmaceutical ingredients. FDA feedback emphasized the importance of demonstrating benefits across both physiological endpoints and patient-reported outcomes in chronic diseases such as OSA.

The DReAMzz study will evaluate multiple ratios of dronabinol and acetazolamide to identify the optimal formulation that delivers consistent improvements across objective sleep and respiratory endpoints while maintaining patient-reported benefits and a favorable safety profile. The study design was developed with input from the company’s Obstructive Sleep Apnea Clinical Advisory Board and has been reviewed by the FDA. Incannex has appointed a contract research organization and expects to begin dosing patients in the coming months.

Results from the DReAMzz study are expected to enable Incannex to advance into a highly efficient phase 3 development program, potentially conducted under a single master protocol comprising parallel studies. By refining the optimal dose before phase 3, the company aims to reduce overall development costs and maximize the probability of clinical and regulatory success.