Strike 3: Aptinyx's pain prospect flunks 3rd midphase trial, sending stock to the basement

The prospects for Aptinyx’s NYX-2925 keep getting bleaker. Having flunked a phase 2b painful diabetic peripheral neuropathy (DPN) clinical trial in April, the therapy has now missed the mark in a fibromyalgia study.

Investigators randomized 305 fibromyalgia patients to receive placebo or one of two doses of NYX-2925, an oral NMDA receptor positive allosteric modulator. After 12 weeks of daily dosing, Aptinyx compared the change on an assessment of average pain intensity in the past 24 hours in the three cohorts. Neither dose of NYX-2925 outperformed placebo, causing the study to miss its primary endpoint.

At Week 4, Aptinyx saw “a trend toward clinically meaningful improvement in pain, as well as in some secondary endpoints” versus placebo. However, placebo caught up over the following weeks. By Week 12, NYX-2925 was numerically better than placebo, but the difference was neither statistically significant nor clinically meaningful.  

“We are very disappointed that, despite the evidence of activity observed in a prior biomarker study in fibromyalgia patients, in this follow-up phase 2b study NYX-2925 did not achieve statistical separation from placebo,” Aptinyx CEO Andy Kidd, M.D., said in a statement. “The results of this study highlight the challenges of developing novel therapies for pain.”

Aptinyx is now well versed in those challenges. In 2019, NYX-2925 failed a phase 2 painful DPN trial, but Aptinyx kept going, kicking off a second midphase trial in the same indication and the fibromyalgia trial. The second DPN trial failed in April. Now, with NYX-2925 failing in fibromyalgia, the drug candidate may have reached the end of the road, although Aptinyx is still evaluating the data. 

Whatever happens to NYX-2925, Aptinyx has chances to improve its fortunes in the coming months. Data from an exploratory phase 2 study of NYX-458 in patients with cognitive impairment are due in the first quarter of next year, with results from a phase 2b PTSD trial of NYX-783 scheduled to follow in the back half of 2023. 

Aptinyx calculates its $85 million cash reserve will keep it going into 2024. While the biotech has funding to take it beyond the clinical readouts, the earlier setbacks have weakened its ability to raise more cash from public investors. Aptinyx's shares dropped 35% after the news broke, reaching below 40 cents in premarket trading Friday compared to a close of 60 cents.