Incannex Healthcare Completes Phase 2 Enrollment in RePOSA Phase 2/3 Trial of an Oral Once-Daily Treatment for Obstructive Sleep Apnea

Incannex Healthcare Inc recently announced it has completed Phase 2 patient enrollment in the global Phase 2/3 RePOSA study of IHL-42X for the treatment of Obstructive Sleep Apnea (OSA). IHL-42X is an oral fixed dose combination medicine designed to reduce the incidence of interruptions to breathing during sleep and improve sleep quality.

“We are excited to have achieved this milestone and deeply grateful to our investigators, site coordinators, and, especially to the sleep apnea patient community for its support. The pace at which we fully enrolled the Phase 2 portion of the RePOSA Phase 2/3 study strengthens our confidence in this program. OSA is a serious, chronic, and life-threatening condition, and we believe our once-daily oral medication – designed to target underlying causes of OSA – could offer meaningful benefits to patients,” Lou Barbato, M.D., Chief Medical Officer of Incannex.

“What makes IHL-42X truly unique is that it’s the first new therapeutic in its class to target physiological pathways directly tied to the airway obstruction and CO₂ accumulation, both of which are characteristic of OSA. We are eager to report topline clinical data from Phase 2 portion of the study and progress to the larger Phase 3 as swiftly as possible,” said Mark Bleackley, Ph.D., Chief Scientific Officer of Incannex.

“We are pleased to have completed Phase 2 recruitment in the IHL-42X RePOSA clinical trial. The speed at which patients enrolled in the study was impressive, surpassing typical recruitment timelines for trials of this nature. This strong interest underscores the pressing need for more effective pharmaceutical options to manage OSA,” said Mira Baron, M.D., a lead investigator for the RePOSA Phase 2/3 trial, Palm Beach Research Center. “Despite the widespread global prevalence of obstructive sleep apnea, there is still no approved pharmaceutical therapy specifically for the treatment of OSA. The positive response from both clinicians and patients reflects the real-world demand for a well-tolerated and effective therapeutic option. IHL-42X represents an exciting and novel approach for filling this longstanding treatment gap. I look forward to seeing the progress we are making in partnership with Incannex to further advance this program and address a critical need in sleep medicine.”

The RePOSA Phase 2/3 is a randomized, double-blind clinical trial designed to evaluate the safety and efficacy of IHL-42X in patients with mild to severe OSA, who are intolerant, non-compliant, or naïve to positive airway pressure (PAP) therapy. At least 560 patients will be recruited, with a total of 355 patients receiving IHL-42X over the course of the study.

The Phase 2 study is a four-week, dose-finding study comparing two dose strengths of IHL-42X (2.5 mg dronabinol/125 mg acetazolamide and 5 mg dronabinol/250 mg acetazolamide) to placebo. More than 120 patients were enrolled across 11 study sites in the U.S. Phase 2 results will determine the optimal dose strength to advance into the larger Phase 3 trial.

The Phase 3 expansion study will evaluate the selected IHL-42X dose over 52 weeks, comparing it to its individual active pharmaceutical ingredients, dronabinol and acetazolamide, at equivalent doses, and to placebo. This pivotal study will enroll approximately 440 patients across four treatment arms, with the goal of supporting future regulatory submission and providing a potential new treatment option for patients with OSA who are underserved by current therapies. Phase 2 trials sites will be rolled over into the Phase 3 expansion study, allowing for an efficient transition and minimizing downtime between study phases.

The Phase 2/3 study follows a recently completed successful pharmacokinetic (PK) study designed to support a future FDA 505(b)(2) new drug application (NDA) and aid in the analysis of the global Phase 2/3 RePOSA study data, in addition to an earlier Phase 2 clinical proof-of-concept trial. Additional information about the RePOSA study can be found at www.clinicaltrials.gov under trial identifier NCT06146101.

Obstructive sleep apnea is a chronic, serious, and life-threatening condition characterized by frequent interruptions in breathing. Individuals with OSA experience apneic episodes, waking up gasping for air 15 to 30 times per hour. During apneic episodes, collapse and obstruction of the upper airway lead to intermittent cessation of breathing, hypoxia (low oxygen levels), and hypercapnia (inadequate expulsion of carbon dioxide). This results in poor quality of sleep, severe and daytime fatigue, insomnia, difficulty concentrating, and irritability. OSA is also linked to serious medical conditions, including high blood pressure, heart disease, Type 2 diabetes, metabolic syndrome, liver disease, and complications with medicines and during surgery.

More than 54 million adults in the U.S. and 936 million worldwide suffer from OSA, with prevalence on the rise due to aging populations, obesity, metabolic syndrome, and sedentary lifestyles. Public awareness is increasing, along with advancements in professional and consumer diagnostic technologies, contributing to earlier diagnosis and treatment. Notably, approximately 20% of adults with OSA are non-obese, and they are four times more likely to develop hypertension compared to obese individuals without OSA.

Current treatment options for moderate-to-severe OSA, such as continuous positive airway pressure (CPAP) devices and an injectable GIP/GLP-1 agonist for patients with obesity, have significant drawbacks in terms of long-term use and patient compliance. CPAP devices, which deliver pressurized air through a fitted mask worn during sleep, and current pharmacotherapy often face challenges with adherence and discontinuation. For patients who fail to comply with, or are intolerant of these treatments, surgical removal of excess throat tissue to widen the airway may be considered. However, success rates vary, and there are potential risks of surgical, as well as long-term post-surgical complications.

IHL-42X is designed to treat OSA by targeting its underlying pathophysiology. An oral fixed-dose combination of dronabinol and acetazolamide, IHL-42X is currently advancing through the RePOSA Phase 2/3 clinical trial, which is expected to enroll more 560 patients at sites worldwide.

Designed to act synergistically, IHL-42X uniquely targets two physiological pathways associated with the intermittent hypoxia (IH) and hypercapnia that characterize OSA. In a prior Australian Phase 2 clinical trial, IHL-42X was shown to reduce the Apnea-Hypopnea Index (AHI) in all dosage strengths, with the lowest dose reducing AHI by an average of 51 percent relative to baseline. RePOSA, a global Phase 2/3 clinical trial is underway, evaluating IHL-42X in individuals with OSA who are either non-compliant, intolerant, or naïve to positive airway pressure devices, including CPAP, with the Phase 2 portion conducted in the United States. A topline readout from the U.S. Phase 2 portion is anticipated in the first half of 2025.

Incannex is leading the way in developing combination medicines that target the underlying biological pathways associated with chronic conditions, including obstructive sleep apnea, rheumatoid arthritis and generalized anxiety disorder. The company is advancing three clinical-stage product candidates based on evidence-based innovation, and supported by streamlined operations. Incannex’s lead clinical program, IHL-42X, is an oral fixed-dose combination of dronabinol and acetazolamide designed to target underlying mechanisms and act synergistically in the treatment of obstructive sleep apnea. In a Phase 2 development program, IHL-675A is an oral fixed-dose combination of cannabidiol and hydroxychloroquine sulfate designed to act synergistically to alleviate inflammatory conditions, such as rheumatoid arthritis. Approved for Phase 2 clinical development, PSX-001 is an oral synthetic psilocybin treatment for the treatment of generalized anxiety disorder. Incannex’s programs target disorders that have limited, inadequate, or no approved pharmaceutical treatment options. For additional information on Incannex, please visit our website at www.incannex.com.