Aptinyx said today it will weigh its next steps in developing its lead candidate NYX-2925 after it failed a Phase II trial in people with painful diabetic peripheral neuropathy (DPN)—news that caused the company’s stock to lose more than two-thirds of its value in premarket trading.
The company acknowledged that NYX-2925 missed its primary endpoint in the Phase II study (NCT03219320), based on topline results.
NYX-2925 failed to show statistically significant improvement compared to placebo when it came to a change in participants’ average daily pain scores on the Numerical Rating Scale (NRS) at week four of treatment compared to baseline, Aptinyx said.
Of the three dose levels evaluated, the 50 mg dose showed the most meaningful improvements across multiple measures, Aptinyx said—including a 1.61-point reduction from baseline in average daily pain on the NRS, the largest such reduction among the dose levels evaluated. However, the reduction was not statistically significant from the 1.23-point reduction observed in the placebo group.
Participants receiving NYX-2925 at 50 mg also had clinically meaningful trends of improvement on key secondary endpoints, including sleep and pain on walking, Aptinyx said. No plateau in the effect of NYX-2925 at 50 mg was observed by the end of the four-week study, which according to the company suggested that a longer treatment duration may result in a stronger analgesic effect.
The next-greatest improvement was seen in participants receiving the 200 mg dose. NYX-2925 was well tolerated among patients and showed no serious adverse effects, Aptinyx added.
The Phase II trial was a randomized, double-blind, placebo-controlled study in which 300 subjects with painful DPN received daily oral doses of placebo or NYX-2925 at 10 mg, 50 mg, or 200 mg over the course of four weeks. All subjects in the study had moderate to severe pain at baseline.
Key secondary endpoints in the study included worst daily pain, pain on walking, and sleep interference. The company plans to present detailed results from the study at an unspecified upcoming medical meeting.
71% stock plunge
“We will continue to interrogate the full dataset to determine the most appropriate path forward for NYX-2925 in development for chronic pain,” said Aptinyx president and CEO Norbert Riedel, PhD. “While the study did not meet its primary endpoint, we observed improvements on multiple measures, differential activity across dose levels, and a very favorable safety profile.”
Investors responded to Aptinyx’ clinical trial failure, with a stock selloff that sent the company’s shares on the NASDAQ Global Select Market plunging 71% in premarket trading from yesterday’s closing price of $17.83 a share, to $5.11 as of 10:23 a.m.
NYX-2925 is a novel NMDA receptor (NMDAr) modulator that the company said has shown robust activity in preclinical models of numerous neuropathic pain conditions with a favorable tolerability profile. In a Phase I trial in healthy human participants (NCT02834741), NYX-2925 was well tolerated across a wide dose range, including dose levels well in excess of the expected therapeutic levels, Aptinyx said.
Last month, Aptinyx trumpeted positive interim data from the first 11 subjects who completed an exploratory Phase II study in fibromyalgia (NCT03249103). The company said that administration of NYX-2925 resulted in statistically significant effects on the primary endpoint—changes in markers of central pain processing as measured by advanced imaging techniques—including changes in combined glutamate and glutamine (Glx) levels in brain regions that were pre-specified and selected for analysis based on their known involvement in processing pain.
Aptinyx said it expects to announce data from the full analysis of that Phase II study in the first half of 2019.
“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,” Riedel said.