NeuroRx plans pivotal trial after seeing hints of efficacy in suicidal patients

NeuroRx is planning to move NRX-101 into phase 2b/3 after detecting signs of efficacy in a feasibility trial in patients with suicidal bipolar depression. The small phase 2 feasibility study linked fixed-dose combination NRX-101 to improved scores on a depression rating scale. 

Delaware-based NeuroRx primarily designed the trial to assess blood level exposure of D-cycloserine and lurasidone, the NMDA antagonist and 5-HT2a receptor antagonist it has combined in NRX-101. NeuroRx thinks the combination may reduce suicidal thoughts by increasing levels of glutamate and glutamine, allowing it to fill a niche that is poorly served by existing serotonin-focused drugs. 

That hypothesis remains unproven. But having included depression as a secondary endpoint in the feasibility study, NeuroRx thinks it has the data to support testing the idea in larger, phase 2b/3 clinical trial that is powered for efficacy.

The supporting evidence comes from an assessment of the effect of NRX-101 on the Montgomery Åsberg Depression Rating Scale (MADRS) scores of people with severe bipolar depression. After being stabilized by a single ketamine infusion, patients who took NRX-101 for two weeks scored 11 points better on MADRS than their counterparts who received the antipsychotic lurasidone.

With the MADRS difference translating into a p value of 0.03 in trial that wasn’t powered for efficacy, NeuroRx is encouraged by the data and is gearing up to run a pivotal phase 2b/3 clinical trial. The case for advancing the drug is strengthened by the unmet needs of the target population. 

"The sad truth is that if you know two people with bipolar depression, on average, one will attempt suicide. If you know five people with bipolar depression, one is likely to succeed," Daniel Javitt, the inventor of NRX-101, said in a statement. "For too long, the only FDA-approved therapy for suicidal depression has been electroconvulsive therapy, which appears to work by raising Glx in the brain." 

There remains considerable scope to doubt how NRX-101 will fare in the phase 2b/3 trial, though. While NeuroRx saw a statistically significant divergence between the treatment and control groups after two weeks, by six weeks the p value had increased to 0.059. 

NeuroRx said separation between the groups was maintained, though, and none of the 10 patients who received NRX-101 suffered from a relapse, a term defined by a 50% or more increase in MADRS over baseline and other factors. Two of the five patients in the control arm relapsed.

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