FDA Declines EUA Request for Zyesami for COVID-19

NRx Pharmaceuticals had been seeking emergency use for Zyesami for COVID-19 respiratory failure. The company will now focus on clinical research for its therapy for patients with bipolar disorder.

The FDA has declined to issue an emergency use authorization (EUA) for NRx Pharmaceuticals’ Zyesami (aviptadil) for COVID-19 respiratory failure in patients who had received remdesivir and continued to progress. The company had submitted this EUA application using data from a post-hoc subgroup analysis.

“Though disappointing, this decision by the FDA is not unexpected, given that they had already recently declined breakthrough therapy designation for Zyesami. We will evaluate the options for Zyesami in COVID-19 respiratory failure and other lung disorders once we receive the full data set from the National Institutes of Health (NIH),” Robert Besthof, interim CEO, NRx Pharmaceuticals, said in a press release.

Zyesami is a synthetic form of human vasoactive intestinal peptide (VIP) is a substance produced by the body that helps protect cells against inflammatory conditions. Early data had suggested that VIP binds to receptors on Alveolar Type II cells in the lung, the same cells that bind the SARS-CoV-2 virus, which inhibit the replication of the SARS-CoV2 virus.

NRx data from one hospital showed that 16 of 19 COVID-19 patients treated with Zyesami under the Right to Try program recovered. And while the data from an NIH-sponsored ACTIV-3b (TESICO) trial showed a mortality advantage, that study did not meet the primary endpoint. In May 2022, that trial was stopped because it didn’t meet its objectives.

The company indicated in a press release that it will now focus on its bipolar drug candidate, NRX-101. The drug, which is being developed specifically for patients with acute bipolar disorder (requiring hospitalization) and sub-acute (not requiring hospitalization), had been paused during the pandemic.

The company has begun a phase 2 study of NRX-101 in patients with bipolar depression and subacute suicidality. A phase 2b/3 study in patients with bipolar depression and acute suicidal ideation is expected to begin later this year.

NRX-101 is an oral fixed-dose combination of two FDA-approved drugs: d-cycloserine, an NMDA receptor modulator; and Latuda (lurasidone), a 5-HT2a receptor antagonist. D-cycloserine is an antibiotic used to treat patients with tuberculosis but it has also been studied to treat patients with anxiety because it is thought to affect certain receptors in the brain. Latuda, developed by Sunovion, is used to treat patients with schizophrenia.

The FDA has granted the combination therapy a breakthrough therapy designation (BTD) for the treatment of severe depression and acute suicidal ideation and behavior in patients with bipolar depression.