Apnimed, a clinical-stage pharmaceutical company focused on developing oral pharmacologic treatments to address obstructive sleep apnea (OSA) and related disorders, today announced 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.
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. HB 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,” said Larry Miller, M.D., Chief Executive Officer of Apnimed. “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.”
Dr. Miller continued by saying, “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.”
Apnimed also issued a press release today showcasing results from a second Phase 2 study, APC-004, exploring the safety and efficacy of AD109 in patients with mild to moderate OSA. For more information on that announcement, click here.
Study APC-003 and Open Label Extension Data Summary: A Phase 2 Clinical Trial in Patients with Mild to Severe OSA (NCT04580394)
This Phase 2 study was a randomized, double-blind, placebo-controlled, four-period, single-dose crossover factorial study in patients with mild to severe OSA. A total of 60 participants were enrolled. At bedtime during four overnight periods, each participant received one night of AD109, one night of each of the individual components that make up AD109 (aroxybutynin and atomoxetine), and one night of placebo.
Patients treated with AD109 had a large, statistically significant, and clinically meaningful difference from placebo in their HB (p<0.001). HB was the primary endpoint of the study and measures the total amount of respiratory event-related hypoxemia during sleep. A growing body of evidence supports HB as the most meaningful predictor of adverse cardiovascular outcomes in patients with OSA. Similar results were seen for AHI (p=0.002), which indicates the number of apnea and hypopnea events per hour of sleep. AD109 was found to be safe and well-tolerated. In a post-hoc analysis, a subgroup of patients with baseline AHI≤45 (excluding participants with very severe OSA) was identified that demonstrated even larger objective effects on HB and AHI. This subgroup will be studied further in an upcoming Phase 2 study, called MARIPOSA.
In addition, a four-week open-label extension was conducted that confirmed the efficacy and safety findings from the first segment of the study. Over four weeks of treatment with AD109, patients (n=37) had statistically significant and clinically meaningful reductions in HB (p<0.05 vs. baseline) and AHI (p<0.05 vs. baseline). Additionally, the open-label extension portion of the study showed improvement across measures of sleep quality with a statistically significant decrease in the patients’ arousal index at day 28 as compared to baseline (p<0.05). The arousal index represents the number of sleep disturbances per hour.
“The results from Study APC-003 are incredibly promising,” said James Maynard M.D., a principal investigator on the study from CTI Clinical Research Center (Cincinnati, OH). “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.”
The study also demonstrated a statistically significant (p<0.01) four-point improvement in patient-reported outcomes as measured by the OSA-Specific Quality of Life Index (SAQLI), which is a 14-item scale that measures quality-of-life in OSA patients. The SAQLI, along with other patient-reported outcomes, will continue to be studied in upcoming Phase 2 trials.