– Primary and secondary endpoints showed promising results for the treatment of OSA as compared to placebo
– Both candidates demonstrated a favorable safety profile
CAMBRIDGE, Mass. November 16, 2021 – Apnimed, a clinical-stage pharmaceutical company focused on developing oral pharmacologic treatments to address obstructive sleep apnea (OSA) and related disorders, today announced positive topline results from a proof-of-concept randomized, controlled, double-blind, single-dose, three-period crossover study (protocol APX-001) in patients with OSA evaluating AD504 and AD182.
Patients treated with AD504 (atomoxetine plus trazodone) showed a strong trend in the reduction in apnea hypopnea index (AHI) from placebo, which was the study’s primary endpoint. AHI is the number of apneas (cessations of breathing) or hypopneas (shallow breathing) per hour of sleep. Additionally, the study’s secondary endpoint was met with a significant reduction of sleep apnea specific hypoxic burden (HB) following treatment with AD504. HB is a measure of the total amount of respiratory event-related hypoxemia and a growing body of evidence supports HB as the most meaningful predictor of adverse cardiovascular outcomes in patients with OSA. A second drug, AD182 (atomoxetine and an orexin antagonist) was also studied and demonstrated a positive trend in the reduction of HB.
“We’re pleased with the reduction in HB demonstrated by AD504 in this small, proof-of-concept, Phase 2 study,” said Larry Miller, M.D., Chief Executive Officer of Apnimed. “In our pursuit to deliver breakthrough oral medications to patients with OSA, we are exploring multiple drug combinations and patient subpopulations. This drug combination involving a medication commonly prescribed for sleep problems could particularly benefit OSA patients with disturbed sleep – difficulty initiating and maintaining sleep – which we believe represents an important sub-population of OSA patients.”
Dr. Miller continued by saying, “On the heels of positive data across two Phase 2 studies with our lead program, AD109 (atomoxetine and aroxybutynin), we are initiating a Phase 2 confirmatory study, called MARIPOSA, in the coming weeks. While AD109 will be the focus of MARIPOSA, we also have the opportunity in this study to further explore the potential of AD504.”
Study APX-001 Data Summary: A Phase 2 Clinical Trial Exploring AD504 and AD182 in OSA Patients (NCT04645524)
This was a proof-of-concept, randomized, controlled, double-blind, single-dose, three-period crossover study of 15 patients who met eligibility criteria. Each patient received one night of AD504 (atomoxetine and trazodone), one night of AD182 (atomoxetine and an orexin antagonist), and one night of placebo. Doses were given immediately prior to bedtime.
AD504 showed a strong trend in reduction of AHI from placebo (from 18.2[11.8-31.3] events/hour to 7.4[5.4-16.1] events/hour, p=0.06) and a significant reduction in HB from placebo (from 48.2[31.2-79.6] to 18.7[14.9-43.5] %min/hour, p<0.001). AD182 also demonstrated a trend towards reduction in HB relative to placebo. Both combination drugs also demonstrated a favorable safety profile.
An investigational, oral pharmacologic combination dosed once daily at bedtime, AD504 may be beneficial for OSA patients who also experience sleep disturbance. AD504 is Apnimed’s second core program and is a combination of atomoxetine and trazodone. Additional Phase 2 development of AD504 will be incorporated in the MARIPOSA study. Apnimed is developing proprietary formulations of the AD504 combination.
About Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA) is one of the most common and serious sleep disorders and is estimated to affect more than 25 million Americans, though underdiagnosis continues to be a serious problem. OSA is characterized by partial or complete upper airway closure that occurs during sleep, which often leads to poor sleep, and in the long-term has been shown to exacerbate hypertension, diabetes, cardiovascular disease, and stroke. Additionally, OSA can impair work productivity, reduce functional ability, and lower quality of life.
Sleep-related muscular relaxation driven by the central nervous system is the key neurologic mechanism leading to OSA. In patients with OSA, sleep onset leads to a reduction in neuromuscular control of the upper airway and a corresponding relaxation of the upper airway dilator muscles. The vast majority of diagnosed patients are prescribed positive air pressure therapy devices such as continuous positive airway pressure, or CPAP, but many patients are dissatisfied with these mechanical nighttime devices and fewer than half are compliant long-term, leaving a significant population untreated, undertreated, and at risk.
Apnimed is a clinical-stage pharmaceutical company working to transform the treatment of sleep apnea based on a simple idea – patients with obstructive sleep apnea will benefit from treatment with a safe and effective oral medication. Apnimed’s lead development program targets the neurologic control of upper airway muscles to maintain an open airway during sleep. The drug is delivered as a convenient once-daily oral pill that can be taken at bedtime. Based in Cambridge, Mass., the company is developing a portfolio of novel pharmacologic therapies for sleep apnea and related disorders. Learn more at apnimed.com.