Apnimed, a clinical-stage pharmaceutical company focused on developing oral pharmacologic treatments to address obstructive sleep apnea (OSA) and related disorders, reports positive data across multiple endpoints from a Phase 2 randomized, double-blind, placebo-controlled, four-period, single-dose crossover factorial clinical trial (APC-003), and a 28-day open-label extension study, evaluating AD109 as a treatment in patients with mild to severe OSA.

AD109 is Apnimed’s investigational, oral pharmacologic combination dosed once daily at bedtime, designed to treat OSA patients across a broad spectrum of disease severity. AD109 targets key neurological pathways in OSA that cause pathological upper airway closure during sleep. AD109 combines a selective norepinephrine reuptake inhibitor (atomoxetine) with Apnimed’s novel new chemical entity—a selective antimuscarinic (aroxybutynin).

The randomized, placebo-controlled segment of the study showed that AD109 had a statistically significant and clinically meaningful difference from placebo after a single dose in the patients’ hypoxic burden (HB), which was the study’s primary endpoint. Hypoxic burden is a measure of the total amount of respiratory event-related hypoxemia, or low blood oxygen during sleep. The apnea-hypopnea Index (AHI), which was a secondary endpoint, which indicates the number of apnea (cessation of breathing) and hypopnea (shallow breathing) events per hour of sleep, demonstrated a similar reduction for AD109 relative to placebo. Additionally, during the open-label extension phase of this clinical trial, AD109 was shown to have a durability-of-effect when patients took AD109 for 28 days. Patients also experienced improvements in quality-of-life, nighttime breathing, and sleep across both objective and subjective measures.

“Today, we announced the findings from two key studies with our lead program AD109, which looked at two different populations of patients with OSA and different parameters of efficacy,” says Larry Miller, MD, Apnimed CEO, in a release. “Both of these studies demonstrate the potential of this oral pharmaceutical option to have a positive impact for patients in need of safe and easy-to-use solutions to address their disease. The results of Study APC-003 and its open-label extension provide strong evidence of durability-of-effect over 28 nights of treatment with AD109 and demonstrate improvements in the quality of the patients’ sleep across several key measures.

“Importantly, the open-label extension also looked at the impact of AD109 on the patient’s quality-of-life, using a gold standard assessment, the OSA-Specific Quality of Life Index (SAQLI), where patients reported statistically significant improvements in quality of life that suggest meaningful improvement in symptoms with chronic treatment. We look forward to confirming these findings and those of Study APC-004 in our planned Phase 2 MARIPOSA clinical trial, which will begin later this year.”

“The results from Study APC-003 are incredibly promising,” says James Maynard MD, a principal investigator on the study from CTI Clinical Research Center. “With AD109 we are seeing clinically meaningful improvement in oxygenation and breathing during sleep as well as indications that these measures are improving over time, signaling the potential to see greater benefit the longer patients are on an oral treatment approach.”

Apnimed also reports results from a second Phase 2 study, APC-004, which explores the safety and efficacy of AD109 in patients with mild to moderate OSA.

This Phase 2 randomized, double-blind, placebo-controlled, crossover clinical trial shows positive data across multiple endpoints.

Patients treated with both the high and low doses of AD109 had a large, statistically significant, and clinically meaningful difference from placebo after a single dose in their hypoxic burden. AHI, a secondary endpoint, demonstrated a similar reduction on both high and low doses of AD109. Treatment with AD109 was safe and well tolerated at both doses studied.

“We are extremely encouraged by these results which continue to reinforce the potential of AD109 to have a clinically meaningful benefit for patients with mild to moderate OSA,” Miller says. “Both doses studied in this clinical trial led to statistically significant improvements across multiple measures of disease severity and demonstrated clear evidence of a dose-response.

“These data, combined with that of our Phase 2 study, APC-003, in a patient population with more severe disease, support the further advancement of AD109 as the first pharmacologic treatment for patients with a range of OSA severity. We plan to initiate a third Phase 2 confirmatory study, called MARIPOSA, which is slated to start later this year. MARIPOSA will help us finalize the trial design and the doses for our Phase 3 program, which we anticipate initiating at the end of 2022.”

Russell Rosenberg, MD, the principal investigator on the study from Neurotrials Research, says in a release, “Many OSA patients go untreated because the currently available treatment options can be uncomfortable and cumbersome, leaving patients at risk for potentially debilitating adverse health outcomes. These AD109 data are the first evidence of a clinically meaningful benefit from a pharmacologic approach to treating OSA, which if successful could be a revolution in the way we treat this highly burdensome disease which can have a major impact on the health of afflicted individuals.”

Photo 135525590 © motortion | Dreamstime.com