Aptinyx’s Mid-Stage NMDA Receptor Fails to Hit Endpoints in Neuropathic Pain Study

Shares of Illinois-based Aptinyx have plunged more than 67 percent in premarket trading after the company announced its mid-stage treatment for painful diabetic peripheral neuropathy failed to show statistical significance.

Aptinyx’s NYX-2925 is a novel NMDA receptor, which earned Fast Track designation from the U.S. Food and Drug Administration for the treatment of neuropathic pain associated with DPN. People suffering from neuropathic pain are currently treated with a variety of therapies including antidepressants, anticonvulsants and opioids. The medications typically used do not provide the best relief and often are poorly tolerated due to side effects. In the Phase II trial, NYX-2925 did not demonstrate statistically significant separation from placebo on the primary endpoint, change in subjects' average daily pain scores on the Numerical Rating Scale.

The Phase II trial was evaluating three dose levels of NYX-2925, 10 mg, 50 mg or 200 mg. Of those three dose levels, Aptinyx said the 50 mg dose showed the most meaningful improvements across multiple measures. Patients in the trial were given one of the dose levels of NYX-295 or placebo for four weeks.  All subjects in the study had moderate to severe pain at baseline and the primary endpoint of the study was the mean change in average daily pain, as measured by the NRS.

Aptinyx said the 50 mg and 200 mg dose levels demonstrated the greatest improvements from baseline, with the 50 mg dose showing “numerical superiority.” The group treated with 50 mg of NYX-2925 showed a 1.61-point reduction from baseline in average daily pain on the NRS. However, the company noted that it was not a statistically significant improvement from the 1.23-point reduction observed in the placebo group. Subjects receiving NYX-2925 at 50 mg also had clinically meaningful trends of improvement on key secondary endpoints, including sleep and pain on walking, the company said.

Norbert Riedel, president and chief executive officer of Aptinyx, said that although the Phase II study did not meet endpoints, the company saw improvements on multiple measures with NYX-2925.

“Coupled with the positive evidence of biological activity relevant to central pain processing from our recently announced interim analysis of a fibromyalgia study, we believe the total body of clinical data indicates the potential of NYX-2925 to treat chronic pain. We will continue to interrogate the full dataset to determine the most appropriate path forward for NYX-2925 in development for chronic pain,” Riedel said in a statement.

While the Phase II trial failed, Aptinyx will continue to review the data in order to determine the most appropriate path forward for NYX-2925. Aptinyx plans to present detailed results from this study at an upcoming medical meeting. In addition to painful diabetic peripheral neuropathy, Aptinyx is also examining NYX-2925 in an exploratory Phase II study in subjects with fibromyalgia. An interim analysis of this study showed “promising evidence of activity on both objective and subjective measures.” The company said it anticipates announcing full data from this trial in the first half of 2019.

Additionally, Aptinyx has other programs in its pipeline, including NYX-783 for the treatment of post-traumatic stress disorder and NYX-458 for the treatment of Parkinson's disease cognitive impairment.