Some investors might love biotech stocks for their lottery ticket-like returns when a company strikes medical gold. A lottery ticket, however, costs only a buck or two, while getting a biotech company wrong can hurt a lot more than that. Case in point: Aptinyx (APTX) shares are collapsing in early-morning trading on Wednesday, falling nearly 66%. The reason? The clinical-stage biopharmaceutical company disclosed disappointing results from its Phase 2 clinical study of NYX-2925 in subjects with painful diabetic peripheral neuropathy (DPN).
In the study, 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 (NRS) during the final treatment week compared to baseline. Of the three dose levels evaluated, 50 mg showed the most meaningful improvements across multiple measures. NYX-2925 was well tolerated in the study with no serious adverse events.
In the randomized, double-blind, placebo-controlled study, 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. Subjects were randomized in a 1:1:1:1 ratio. Baseline values for each endpoint were measured over the seven-day period prior to randomization. All subjects in the study had moderate to severe pain at baseline. The primary endpoint of the study was the mean change in average daily pain, as measured using the NRS (on which 0 represents no pain and 10 represents worst pain imaginable), at week four of treatment compared to baseline. Key secondary endpoints in the study included worst daily pain, pain on walking, and sleep interference.
In the study, the 50 mg and 200 mg dose levels of NYX-2925 showed 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, the largest such reduction among the dose levels evaluated. This improvement did not separate statistically (p=0.1586) from the 1.23-point reduction observed in the placebo group. No plateau in the effect of NYX-2925 at 50 mg was observed by the end of this four-week study, suggesting a longer treatment duration may result in a stronger analgesic effect. Subjects receiving NYX-2925 at 50 mg also had clinically meaningful trends of improvement on key secondary endpoints, including sleep and pain on walking.
In a pre-specified subset of subjects who were not taking a concomitant medication, those treated with NYX-2925 across all dose levels showed improvements relative to placebo on pain and other endpoints that were greater than those observed in the overall study population.
“This four-week proof-of-concept study of our novel NMDA receptor modulator, NYX-2925, in painful DPN was designed to evaluate a 20-fold dose range, determine whether efficacy and dose response could be observed on primary and secondary endpoints, and assess safety in a patient population,” said Norbert Riedel, Ph.D., president and CEO of Aptinyx. “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. 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. Our talented team also remains steadfastly focused on continued execution across our other pipeline programs, including NYX-783 for the treatment of post-traumatic stress disorder and NYX-458 for the treatment of Parkinson’s disease cognitive impairment. Our strong balance sheet will fund our execution and achievements on these programs in 2019 and 2020.”
“We are in the midst of a major societal and healthcare crisis in the treatment of pain and many patients currently lack therapeutic options that do not have significant side effects or abuse potential,” said John T. Farrar, M.D., Ph.D., Associate Professor of Epidemiology at the University of Pennsylvania. “The intriguing efficacy signals and favorable safety profile observed in this study merit further investigation and analysis in order to fully understand the potential of this drug.”
Aptinyx has a few disappointed bulls out today as the stock plummets. According to TipRanks, out of 3 analysts polled in the last 6 months, all 3 are bullish on the stock. The 12-month average price target stands at $36, marking a nearly 487% upside from where the stock is currently trading. (See APTX’s price targets and analyst ratings on TipRanks)