Sleep apnea in the pill: FDA submission phase of Apnimed Drug's Phase 3 Dataset Phase
Standard treatment for respiratory problems caused by obstructive sleep apnea is a medical device. But many find it uncomfortable to wear masks of continuous positive airway pressure (CPAP) machines. Apnimed's experimental drug could provide an easier alternative, and the pill is now a key research-generated by startups that said FDA submitted support plans. It could end up challenging a big pharmaceutical giant.
Apnimed's approach to obstructive sleep apnea (OSA) is targeted at muscles you may not realize. This situation affects an estimated 80 million people in the United States, causing repeated collapse of the upper airway during sleep, resulting in a period of interruption of breathing and intermittent periods of oxygen deprivation. Anatomic abnormalities contribute to the operation and surgery provides a (albeit invasive) approach to the disease. Another reason for OSA is muscle dysfunction that controls the airway.
The APNIMED drug AD109 combines two compounds: the company's new anti-toxic small molecule called Aroxybutynin, and the old attention deficit/ADHD drug atomoxetine (Brand Name Strattera). This pairing is a single pill taken every night before going to bed. According to Cambridge, Massachusetts, the synergy between the two drug components of AD109 is a nervous system pathway that activates muscles in the upper airway to keep it open during sleep. APNIMED co-founder and CEO Larry Miller said in an email that AD109 was found from Brigham & Women's Hospital (BWH) and this combination works for treating OSA. This finding is consistent with previous studies showing that these drug categories can regulate the activity of the brain portion that controls the upper respiratory tract muscle.
“In early studies of BWH that place electrodes in tongue muscles during sleep, researchers were able to directly demonstrate that these drug categories can increase muscle tone on the respiratory tract and reduce airway obstruction,” Miller said.
The results of the trial announced Monday came from a Phase 3 test that recruited 646 adults in the U.S. and Canada who had mild, moderate or severe OSA and could not tolerate CPAP treatment or rejection. Participants were randomly assigned to receive study medication or placebo and taken nightly. The main goal is to measure changes in the apnea index over a six-month period, which is used to measure the scale of decreased or interrupted breathing during sleep (higher scores, the more severe OSA).
APNIMED reported that the average reduction in the apnea index scores in the study drug group was 55.6%, “significantly improving oxygenation and reduced disease severity.” For the placebo group, the average reduction in scores was 19%. The company said AD109 has good tolerance and adverse events are consistent with earlier tests. The most common adverse events reported by the four-week phase 2 study were dry mouth, insomnia, and urine hesitation.
Apnimed said the full-stage results will be presented at a medical conference later this year and will be published in a peer-reviewed journal. AD109 development plans include a Phase 2 trial, which tests drugs for one year in OSA patients. APNIMED is expected to obtain preliminary data from this study in the third quarter of 2025. Through data from two studies, the company plans to submit an FDA submission of AD109 in early 2026. Miller notes that OSA has affected more than 1 billion people in the world. He said the APNIMED program also explores ways to make AD109 available for these patients.
In the second half of last year, there was already a sleep apnea drug in the United States, and Eli Lilly's blockbuster obesity drug Zepbough expanded its label to become the first FDA-approved drug for moderate to severe OSA. The once weekly injection of peptides was designed to bind to two intestinal receptors to stimulate metabolic effects, such as weight loss. How Zepbound works in treating OSA is not known, but obesity is a risk factor for the disease. The results of the Zepbound OSA trial showed that the patient lost weight. Weight loss is believed to improve sleep apnea.
Although Zepbound is the first drug to push into the OSA market, it still faces obstacles in this sign. Making peptide drugs is expensive. Furthermore, many patients prefer pills over injections. As a small molecule, AD109 is less expensive to manufacture and can be used as a more patient-friendly pill. But Apnimed is not the only company developing OSA drugs.
Incannex Healthcare has conducted a phase 2/3 test with IHL-42X, a combination of two older drugs: acetazolamide, a carbonic anhydrase inhibitor whose FDA-approved uses include the treatment of Glaucoma and epilepsy and epilepsy, as well as Nausea and Nausea and vomiting and vomiting and vomiting nausition, and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting and vomiting. The company believes that Dronabinol's activity on cannabinoid receptors can lead to airway expansion. At the same time, acetazolamide signal indicates excessive carbon dioxide in the blood, which has the effect of increasing respiration.
“By combining the two reagents with known reduction mechanisms [apnea-hypopnea index] In one pharmaceutical formula, we believe that IHL-42X may have therapeutic benefits in lower doses of each constituent drug that are safe to bear. ” the company said in its annual report.
Melbourne, Australia-based Incannex is conducting the Phase 2 part of the IHL-42X clinical trial in the United States; the expanded Phase 3 part will include the UK and the EU. The company expects preliminary phase two data in the first half of this year.
Apnimed has a carbonic anhydrase inhibitor of OSA. Last month, it acquired global rights to Sulthiame from German company Desitin Arzneimittel, which has completed a Phase 2 testing of the drug in OSA. Sulthiame can be provided as epilepsy medication in some countries. Miller said the oral small molecule gave an OSA drug candidate different from AD109. The company will develop drugs for OSA and other sleep disorders through a joint venture with Shionogi.
Apnimed's final funding was in 2023, when it raised nearly $80 million to expand its Series C to $142.2 million to fund Phase 3 development of AD109. The company said it has raised $270 million so far.
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