NRx Pharmaceuticals’ NRX-101 shows efficacy in Phase 2b/3 depression trial

NRx Pharmaceuticals’ Breakthrough Therapy designated investigational drug NRX-101 vs lurasidone demonstrated a promising, though not yet statistically significant 33% reduction in suicidality together with a 70% reduction reduction in symptoms of akathisia – a side effect of antidepressants that is closely linked to suicide and considered a medical emergency. In the company’s previous trial, NRX-101 was demonstrated to be superior to lurasidone in reducing both depression and suicidality after ketamine while showing a trend towards reducing akathisia. In this trial, without prior use of ketamine, NRX-101 and lurasidone were comparable in their effect on depression, each reducing depression – the primary endpoint – by about 50% from baseline. Analysis of suicidality demonstrated a sustained 33% advantage in remission from suicidality favoring NRX-101. This difference was not statistically significant at the phase 2 sample size but met the study’s original promising zone criteria and, if sustained in a registration trial of 300 or more patients, would be powered to yield a statistically significant result. The reduction in suicidality is comparable to that demonstrated after ketamine. A meaningful remission in suicidality has not been demonstrated with any prior oral antidepressant drug. While reduction in akathisia is not proposed as a primary labeled indication, continued finding of a statistically significant reduction in this side effect would be highly supportive of a demonstrated primary endpoint of reduced suicidality and would provide clinical corroboration. The FDA recently affirmed to the company that the Special Protocol Agreement for this indication remains in place, subject to the company filing a New Drug Approval for ketamine, which is expected by July.