– Data show favorable safety and pharmacokinetic profile for key component of AD109 –
– Lead program AD109 advancing into a Phase 2 study before year end –
CAMBRIDGE, Mass. September 17, 2020 – (BUSINESSWIRE) – Apnimed, a clinical-stage pharmaceutical company focused on developing medicines to treat sleep apnea and related disorders, today announced the results of a Phase 1 study for a component of the company’s lead combination drug candidate, AD109, which is being explored as a pharmacologic treatment for Obstructive Sleep Apnea (OSA). In this healthy volunteer study, R-oxybutynin, a key component of AD109, demonstrated a favorable pharmacokinetic (PK) profile and was well tolerated with no adverse events related to the study drug.
“Obstructive Sleep Apnea represents a significant public health problem in the U.S. and around the globe and current treatment options do not meet the needs of patients,” said Larry Miller, M.D., chief executive officer of Apnimed. “We believe that AD109, an oral drug candidate dosed once-daily at bedtime, could be a significant breakthrough for these patients by giving them a simple, safe, and effective solution that does not require a CPAP device or surgery. The results from this study support our advancement of this program.”
Miller continued by saying, “we look forward to initiating a Phase 2 study with AD109 in Q4 of this year.”
About the study and results
AD109 consists of the norepinephrine reuptake inhibitor (NRI) atomoxetine combined with the antimuscarinic R-oxybutynin. The study, called APC-001, was a Phase 1, randomized, single-dose, open-label, two-way crossover study conducted to evaluate the safety, tolerability, and PK of 2.5 mg of R-oxybutynin compared to 5 mg of racemic (R,S) oxybutynin in 24 healthy adult volunteers. While S-oxybutynin has been studied as a bladder antispasmodic, most of the antimuscarinic activity of racemic oxybutynin necessary to activate the upper airway muscles and maintain an open airway during sleep is thought to be mediated by R-oxybutynin. By purifying the R-oxybutynin and removing the S-oxybutynin, unwanted bladder effects can potentially be reduced and a lower dose of R-oxybutynin alone, relative to racemic oxybutynin, may be effective to treat OSA.
Study participants received treatments in random order, administered as a single oral dose, with a washout period between treatments of at least 7 days. The results indicated that R-oxybutynin was well-tolerated and that there were no adverse events related to the study drug. The blood plasma concentrations of the 2.5 mg dose of R-oxybutynin, when administered alone, closely matched the profile of R-oxybutynin when dosed as 5 mg of racemic oxybutynin.
Additionally, no interconversion to S-oxybutynin was observed following administration of 2.5 mg R-oxybutynin.
Apnimed’s lead product candidate, AD109, targets neurotransmitter levels in the central nervous system to activate upper airway muscles and maintain an open airway during sleep. AD109 is a first-in-class, oral pharmaceutical combination dosed once-daily at bedtime, designed to treat OSA patients across a broad spectrum of disease severity. The drug is designed to be safe, effective, and convenient, addressing the key limitations of the current standard of care treatments.
Apnimed has successfully completed its first Phase 1 study with AD109 and Phase 2 clinical trials are planned for 4Q 2020. Proof of concept for the AD109 program was demonstrated in Apnimed study APN-002, a Phase 2, parallel group dose-finding study of the combination of atomoxetine and racemic oxybutynin. That study provided evidence of safety and efficacy of a norepinephrine reuptake inhibitor (NRI) + antimuscarinic combination in 140 patients.
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, hypertension, diabetes, cardiovascular disease, strokes, and early mortality. The vast majority of diagnosed patients are prescribed positive air pressure therapy devices such as continuous positive airway pressure, or CPAP, but 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 nighttime neurotransmitter levels in the central nervous system to activate upper airway muscles and maintain an open airway during sleep. The drug is delivered as a convenient once-daily 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