Apnimed sees positives in midstage data for its attempt at drugging the sleep apnea problem

Just a few months after a modest $25 million raise, little Apnimed has released some broadly positive data for its experimental sleep apnea drug.

In obstructive sleep apnea (OSA) patients, muscles that normally keep the upper airway open collapse repeatedly during sleep, causing intermittent low oxygen levels and leading to long-term morbidity and mortality.

Continuous positive air pressure is effective in OSA, but poor adherence to the treatment, which entails wearing a mask during sleep, is suboptimal. Neurostimulation implants are also effective, but some patients are ineligible for the devices and other people are reluctant to undergo the surgical procedure.

Apnimed is betting there is a market for a pharmacological alternative for the estimated 25 million Americans with the disorder, and there are hints that the bet is paying off.

Its drug, AD109, combines a selective norepinephrine reuptake inhibitor (atomoxetine) with Apnimed’s new chemical entity (NCE), a selective antimuscarinic (aroxybutynin), to activate the upper airway dilator muscles and maintain an open airway during sleep.

In data released from a small, 32-patient placebo-controlled crossover phase 2, each patient received low-dose AD109, high-dose AD109 and placebo at bedtime across three overnight periods in randomized order.

The results from the so-called Study APC-004 showed patients treated with both the high and low doses of AD109 saw a “statistically significant and clinically meaningful difference from placebo” after a single dose in their hypoxic burden (HB), which is a measure of the total amount of respiratory event-related hypoxemia, or low blood oxygen during sleep, and was the study’s primary endpoint.

The apnea-hypopnea index (AHI), was a secondary endpoint indicating the number of apnea (cessation of breathing) and hypopnea (shallow breathing) events per hour of sleep, and showed “a similar reduction” on both high and low doses of AD109. The biotech added that the drug was “safe and well tolerated at both doses studied.”

Digging down more into the details, the median HB for participants on placebo was “significantly higher” than for patients on the high dose (p < 0.001) and on the low dose (p < 0.01), Apnimed said.

HB measures the total amount of respiratory event-related hypoxemia during sleep, and the biotech contends that “a growing body of evidence supports HB as the most meaningful predictor of adverse cardiovascular outcomes in patients with OSA.” 

The data also showed a statistically significant and clinically meaningful median reduction in AHI [Median AHI of 13.2 events/h on placebo reduced to a median of 5.5 events/h on the high dose (p < 0.001) and to a median of 7.8 on the low dose (p < 0.05)]. AHI indicates the number of apnea and hypopnea events per hour of sleep.

Caveats remains as full safety and efficacy data have not been shared as yet, a biomarker chosen by the company as a key endpoint can always be risky and it’s only in a handful of patients. As ever, a larger test will be needed to prove its worth.

Apnimed raised a $25 million series B round back in the spring to help finish off its midstage work. The future will see another phase 2, which will run as a confirmatory study, called MARIPOSA, which is slated to start later this year.

MARIPOSA will in turn help the biotech finalize the trial design and the doses for its phase 3 program, which is planned for the end of next year.

“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,” said Russell Rosenberg, M.D., the principal investigator on the study from Neurotrials Research.

“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.”