OSA pharmacotherapy reduces disease severity

Key takeaways:

• A combination of dronabinol and acetazolamide lowered obstructive sleep apnea severity vs. placebo.
• Further studies are planned to find the optimal dose of the combination for patients.

A combination pharmacotherapy for obstructive sleep apnea led to greater reductions in disease severity compared with placebo, according to results from a proof-of-concept phase 2 trial.

According to a press release, IHL-42X (Incannex Healthcare) comprises two ingredients that have been proven to lower apnea hypopnea index (AHI): dronabinol, or synthetic tetrahydrocannabinol (THC), and acetazolamide.

Mark Bleackley

“Incannex’s discovery that dronabinol and acetazolamide act synergistically to treat OSA, reducing AHI and improving patient-reported sleep quality, are the foundations of the IHL-42X development program,” Mark Bleackley, PhD, chief scientific officer at Incannex Healthcare Limited, told Healio. “The company is continuing to develop the IHL-42X drug product with the upcoming global RePOSA clinical trial. Incannex is also constantly assessing data from the program to identify opportunities to expand the already robust intellectual property portfolio for IHL-42X.”

In a phase 2 trial, researchers assessed patients with OSA to determine the safety of IHL-42X and changes in baseline AHI after receiving the treatment against placebo.

Researchers evaluated three different doses of IHL-42X — low (2.5 mg dronabinol and 125 mg acetazolamide), medium (5 mg dronabinol and 250 mg acetazolamide) and high (10 mg dronabinol and 500 mg acetazolamide) — given for four periods of 7 days, each separated by 7-day washout periods.

Patients receiving the IHL-42X doses had lower AHI scores after treatment compared with baseline (average reduction: low, 50.7%; medium, 48.1%; high, 35.2%). Notably, patients in the placebo group did not show a large change in AHI from baseline (average reduction, 6.4%).

According to the release, researchers found a statistically significant difference in AHI between the placebo and IHL-42X dosage groups.

Improvement in AHI was widely apparent in those who received the low dose of IHL-42X. More than half of these patients (62.5%) achieved a drop of more than 50% compared with baseline and a quarter of patients achieved a drop of more than 80%.

“Although we were confident in our hypothesis that IHL-42X would be an effective treatment for OSA, the observation that the lowest dose of IHL-42X led to the greatest reduction in AHI was surprising,” Bleackley told Healio. “It was an exciting result, as using lower doses will reduce the risk of side effects with the drug.”

In addition to better measures of AHI, those receiving the combination treatment also demonstrated improvements in oxygen desaturation index, sleep efficiency and patient-reported sleep quality, according to the release.

“It was encouraging, although, not unexpected, that patients reported better sleep satisfaction and sleep efficiency while receiving IHL-42X than placebo,” Bleackley said. These results indicated that the reduction in AHI was having a meaningful impact on patient’s sleep quality, he continued.

“This provides an important potential treatment option for the substantial proportion of OSA patients who are noncompliant and/or intolerant to positive airway pressure therapy, which is the standard of care for OSA,” Bleackley added. “OSA is associated with an increased risk of cardiac disease and mental health disorders. Reducing AHI is a critical component of decreasing these risks.”

Researchers further noted that the drug appears safe; none of the participating patients reported a serious treatment-emergent adverse event.

The next step in this research is a phase 2/3 (RePOSA) trial that will continue to analyze the safety and efficacy of the low and medium doses of IHL-42X in patients with OSA located in the U.S., Europe and other countries. The FDA cleared the investigational new drug application submitted by Incannex in August 2023.

“The upcoming RePOSA study will extend the treatment period from the 7 days used in the proof-of-concept study to 4 weeks in the phase 2 component and 52 weeks in the phase 3 component,” Bleackley told Healio.

Phase 2 of the RePOSA study will continue to compare IHL-42X doses, Bleackley said. Phase 3 will take the dose that performed best during phase 2 and compare IHL-42X to the component active pharmaceutical ingredients dronabinol and acetazolamide, at equivalent dosages.

“We have also included an expanded set of patient-reported outcomes in the RePOSA study to better capture how patients feel and function in response to IHL-42X,” Bleackley said.

The company “anticipates greatly improved treatment compliance and outcomes from a pharmaceutical product, such as IHL-42X,” according to its webpage for the drug,

Reference:

• IHL-42X Obstructive Sleep Apnoea (OSA). https://www.incannex.com/clinical-trail/ihl-42x-osa/. Accessed Jan. 3, 2024.