Aptinyx Inc. shares (NASDAQ:APTX) fell 66.5 percent to $5.98 on Wednesday after the company's most advanced candidate, NYX-2925, failed to perform much better than a placebo in reducing pain associated with diabetic peripheral neuropathy (DPN) for most patients, missing the primary endpoint of a phase II study. Aptinyx President and CEO Norbert Riedel told BioWorld a deeper analysis of the trial's data is needed before deciding the program's future but that testing the drug in a longer study of DPN patients not on concomitant pain medication might be one potential path forward.

Of three doses tested in the study, a 50-mg dose showed the most meaningful improvements across multiple measures, prompting a 1.61-point reduction from baseline in average daily pain on a numerical rating scale of trial participants' average daily pain scores. The change failed to show a statistically significant separation from the 1.23-point reduction observed in the placebo group (p=0.1586).

The 50-mg dose did, however, demonstrate "a very linear progression of alleviating pain" week after week in the four-week study, Riedel said. "Had I done more of a traditional 12-week study, it is quite likely that the treatment benefit of the 50-mg dose would have continued to provide me with a better delta between the treatment and placebo groups."

Patients in the 50-mg active arm of the study not taking another pain medicine also fared better, in terms of reduced pain, than those taking a concomitant drug — usually gabapentin.

Riedel's other goals for the study, proving the N-methyl-D-aspartate (NMDA) receptor modulator's safety and its secondary benefits, appeared to be met. No drug-related serious adverse events were reported and worst daily pain scores, incidences of pain on walking and sleep interference, all seemed to improve in the 50-mg and 200-mg dose arms, he said.

Evanston, Ill.-based Aptinyx is also testing NYX-2925 in an ongoing phase II fibromyalgia study. An interim analysis of that study yielded evidence of activity on both objective and subjective measures, the company has said.

Aptinyx plans to present detailed results from the study at an upcoming medical meeting.

Analysts down on near-term prospects

Founded in 2015 as a spinout of Allergan plc-acquired Naurex Inc., Aptinyx joined the public market in June 2018. It had $165.5 million in cash and cash equivalents as of Sept. 30. Despite its capacity to carry the program ahead, analysts did not express optimism for the company's near-term prospects. (See BioWorld, May 23, 2018, and June 22, 2018.)

"Given this phase II readout represented the first opportunity to establish POC for '2925 in chronic pain, in addition to the potentially large market opportunity, we view this as a meaningful setback," said J.P. Morgan analyst Jessica Fye. Though maintaining an "overweight" rating on the company's shares, she said that "we believe it would take a positive POC study to reverse the negative sentiment on the stock."

Leerink Partners LLC analyst Geoffrey Porges also voiced disappointment. "Investors are likely to eliminate all value for this program from the company's stock today and thus leave the stock reliant upon earlier programs targeting more challenging disease indications," he said. Those programs include one for cognitive impairment in Parkinson's disease, NYX-458, and NYX-783 for post-traumatic stress disorder.

Meanwhile, competition in diabetic neuropathy marches ahead. Among the most advanced programs in the pipeline according to Cortellis are Yuhan Corp.'s phase III YHD-1119, a sustained-release formulation of the GABA alpha-2-delta subunit agonist pregabalin; Mitsubishi Tanabe Pharma Corp.'s phase II MT-8554; and Celularity Inc.'s human placenta-derived mesenchymal stem cell therapy candidate, cenplacel, also in phase II.