Déjà vu: FDA rejects NRx filing for emergency use in COVID-19

Aviptadil has gone 0 for 2 on emergency use authorization filings at the FDA. The new rejection is the latest in a series of blows to the COVID-19 candidate, driving NRx Pharmaceuticals to shift focus to its bipolar depression prospect. 

NRx first sought an EUA for aviptadil in critical COVID-19 patients suffering from respiratory failure one year ago, only for the FDA to reject the request months later because of a lack of safety and efficacy data. Two months after the rejection, NRx filed again, zeroing in on COVID-19 patients who are at immediate risk of death from respiratory failure despite treatment with approved therapies including Gilead Sciences' Veklury. 

The second attempt ended the same way as the first. Friday morning, NRx revealed the FDA declined to issue an EUA. NRx and its investors were forewarned of the chance of rejection when the FDA knocked back a request for breakthrough designation last month. With expectations low, NRx’s share price, which has fallen 88% this year, barely moved after the latest FDA rejection, sliding 2% in premarket trading to $0.59.

NRx began shifting its attention away from aviptadil before the FDA rejected the breakthrough filing, with the failure of the candidate in the National Institutes of Health's (NIH’s) ACTIV-3b clinical trial serving as the trigger for a rethink of pipeline priorities. The NIH trial stopped its aviptadil arm in May after the drug failed to beat placebo at an interim analysis. Aviptadil, also known as Zyesami, is a synthetic formulation of human vasoactive intestinal peptide.

Success in the NIH study would have positioned aviptadil to join Veklury in the toolkit for treating severe COVID-19. While pursuing that population through the NIH trial, NRx sought to win an EUA for aviptadil in a narrower indication on the strength of a post hoc subgroup analysis.

The back-to-back elimination of both possible paths to market for aviptadil in COVID-19 leaves the future of the program in doubt. NRx plans to evaluate its options once full data from the NIH are received, but for now the focus has shifted elsewhere.

Specifically, NRx is working to get NRX-101 to market in bipolar depression patients with suicidal ideation and behavior. A phase 2 clinical trial of the oral fixed-dose combination of D-cycloserine and lurasidone in patients with sub-acute suicidal ideation and behavior started in May, with a registrational phase 2b/3 study in acute patients set to follow in the second half of the year.

NRx is looking to the studies to reset the narrative after its bruising experience in COVID-19. Data from the phase 2 are due by the end of the year. NRx ended March with $40 million, a sum it expects to fund operations for at least 12 months.