Aptinyx’s approach to modulating the NMDA receptor to treat disorders of the central nervous system has hit a significant snag, as its lead experimental drug failed a mid-stage study in patients with diabetic peripheral neuropathy (DPN), obliterating the recently public company’s stock on Wednesday.
The drug — dubbed NYX-2925 — was developed by the Evanston, IL-based biotech that went public last July banking on its approach to modulate NMDA receptors, which are crucial to brain and nervous system function. The Phase II trial pitted three oral doses of the drug (10 mg, 50 mg, or 200 mg) versus a placebo in 300 patients over four weeks. The experimental treatment failed to confer a statistically significant improvement in average daily pain — as measured by a Numerical Rating Scale (NRS) — at week four, missing the primary endpoint of the study.
The company’s shares $APTX plummeted about 70% in early trading.
The company suggested its 50mg dose had the most promising impact. Patients treated with the dose showed a 1.61-point reduction in average daily pain on the NRS — the largest decrease among the dose levels evaluated — versus the 1.23-point fall in those given the placebo, resulting in a non-statistically significant improvement (p=0.1586). Patients on the 50 mg dose also showed improvement on key secondary endpoints, including sleep and pain on walking, Aptinyx added.
“While the study did not meet its primary endpoint…we believe the total body of clinical data indicates the potential of NYX-2925 to treat chronic pain,” Aptinyx chief Norbert Riedel said in a statement, adding that the company is now in process of finding a way forward for NYX-2925.
“It seems that at best that path forward may consist of another phase II trial in DPN, using the two doses that showed a numerical difference to placebo (50mg and 200mg) and incorporating longer duration of treatment (8 or 12 weeks). Such a study could begin in H2 2019 and produce a result in 2020. However, it is not clear yet whether the company’s board, investigators, advisors and investors will endorse the investment in that (costly) trial. 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 including cognitive impairment in Parkinson’s disease (NYX-458) and post-traumatic stress disorder (PTSD) (NYX-783),” Leerink’s Geoffrey Porges wrote in a note.
In a separate ongoing exploratory mid-stage study, NYX-2925 has shown encouraging results in a small group of patients with fibromyalgia, the company noted in an interim analysis posted last month. The full results of that study are expected in the first half of this year.
“We don’t regard the stock as “dead money” after today’s news, but do recognize that a significant part of its prior valuation is now impaired. Earlier this month the company provided positive biomarker data for NYX-2925 in its other indication of fibromyalgia; at this stage those biomarker effects are encouraging but insufficient,” Porges added.
Various drug developers are focusing on the NMDA receptor, developing compounds to activate or inhibit it to treat CNS disorders, but that strategy has seen a series of setbacks in part due to safety concerns. Aptinyx believes its approach — without ever fully turning the receptor “on” or “off” — will allow it to evade these challenges. Allergan has bought into this Aptinyx philosophy, having licensed their depression drug, which is now called AGN-241751. Aptinyx itself was was spun out of Allergan’s $1.7 billion buyout of Naurex which CEO Brent Saunders wanted for its lead NMDA drug — now dubbed rapastinel — for major depression.
In terms of pain, patients have few effective options other than highly addictive opioids, and therefore drug developers working on non-opioid options are keenly watched. This is likely one of the reasons the FDA granted NYX-2925 fast track status for neuropathic pain associated with DPN.
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