IN-ACTIV: NRx tanks as peptide fails NIH trial in severe COVID-19 patients

There goes another one. After a who’s who of biopharmas failed the National Institutes of Health's (NIH’s) inpatient COVID-19 study, NRx Pharmaceuticals has now flunked a related trial in severely ill patients, sending its share price down to the basement.

The National Institute of Allergy and Infectious Diseases set up ACTIV-3b to determine the effect of drugs in patients hospitalized with life-threatening cases of COVID-19. In the first, and to date only, ACTIV-3b sub-study, the institute tested a combination of aviptadil, Gilead’s remdesivir and a corticosteroid. In the control arm, patients received aviptadil, a corticosteroid and placebo. Aviptadil is a synthetic formulation of human vasoactive intestinal peptide that is also known as Zyesami.

After seeing data on around 460 patients, the monitoring board recommended the sponsor stop the trial because aviptadil failed to meet the futility guidelines. The study was on track to miss its primary goal, which looked at patient status at Day 90 on a six-point scale that ran from death to at home and off supplemental oxygen for 77 or more consecutive days. The p-value at the interim analysis was 0.56.

Aviptadil also failed to beat placebo on a key secondary endpoint. The mortality rate in the aviptadil arm was 37% at the time of the interim analysis, compared to 36% in the placebo group. Robert Besthof, interim CEO of NRx, set out the next steps. 

“We will continue to work closely with [the NIH and the trial leadership] to better understand the data over the coming months.  This will also enable us to evaluate the options for Zyesami in protecting the lung in other respiratory disorders, as well as its potential in other therapeutic areas,” Besthof said in a statement. 

The one positive so far for NRx is that no safety concerns emerged in the trial. NRx said the known side effects of aviptadil, principally diarrhea and low blood pressure, “were managed well with the protocols in place.” 

Shares in NRx crashed by around 40% in premarket trading, dragging the stock price below $1. NRx was trading at above $20 a share one year ago. The biotech ended March with $40.2 million in cash, a sum it expects to support operations for at least the next 12 months. 

The latest hit to NRx’s share price happened on the back of news of the clinical flop and the resignations of its chief corporate and financial officers, Alessandra Daigneault and Ira Strassberg, respectively. The executives both tendered their resignations May 19 and are set to leave the company by July 18 “to pursue other personal and professional interests.”