CEO Update: Denial of Breakthrough Therapy Designation

The US Food and Drug Administration (FDA) denied NRx Pharmaceuticals’ (NRx) request for Breakthrough Therapy Designation (BTD) for ZYESAMI® (aviptadil). BTD is not required for drug approval or emergency use authorization, but can afford faster review times, the ability to submit a rolling application, and dedicated FDA review personnel who may interact more frequently with the sponsor. The FDA already granted the first two benefits (priority and rolling review) as part of the Fast Track Designation awarded in July 2020. This denial, therefore, does not impede NRx’s ability to seek drug approval, although it does identify areas where NRx needs to seek better scientific alignment with the FDA.

In denying BTD, the FDA noted that NRx did not distinguish the effects of ZYESAMI from the reported effects of remdesivir in critically-ill patients. In order to award BTD, the sponsor must present evidence that the candidate Breakthrough Therapy meets an unmet medical need for a serious medical condition. NRx did not review the reported efficacy of other medications in its BTD application largely because ZYESAMI was studied in patients who had already exhausted all approved therapy, including remdesivir.

NRx will comply with FDA’s instruction and will additionally augment its new BTD application with the recently-posted NIH guidelines that identify no benefit associated with the use of remdesivir in the categories of patients represented in NRx’s trial https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults–therapeutic-management/.  

The FDA additionally raised statistical methodology questions that prompted NRx to seek an independent reanalysis of the clinical trial data. NRx has been advised that this analysis confirms the statistical-significance of the survival advantage seen in patients treated with ZYESAMI and looks forward to sharing this new information with the FDA.

Enrollment in the NIH ACTIV-3b trial comparing aviptadil to remdesivir and to placebo continues and has passed the midpoint of the targeted 640 patients. The next meeting of the independent Data Safety and Monitoring Board is scheduled for December 13.