Full Press Release Details
NeuroRx Announces that ZYESAMI (Aviptadil) has Successfully
Demonstrated 10-Day Accelerated Recovery from Respiratory Failure
in Critically Ill Patients with Covid-19 Treated with High Flow
Nasal Oxygen at 28 Day Interim Endpoint
NeuroRx to File for Emergency Use Authorization in This Patient
Population if Positive Results Continue to be Demonstrated at
Day-60 Endpoint in Line with FDA's New Guidance
Pa., Feb. 23, 2021 NeuroRx, Inc. announced
today that the Phase 2b/3 trial1 of ZYESAMI
(aviptadil, previously RLF-100 ) for the treatment of
Respiratory Failure in critically ill patients with
has demonstrated multidimensional benefit around its prespecified
primary endpoint of Recovery from Respiratory Failure with
discharge from hospital and ICU (without relapse) by day 28 in
patients with critical Covid-19 who were treated with High Flow
Nasal Oxygen. Although not envisioned at the start of the clinical
trial, High Flow Nasal Oxygen has become the predominant form of
treatment in Covid-19 respiratory failure, with mechanical
ventilation reserved for those whose blood oxygen levels cannot be
maintained on this less invasive modality. The trial was conducted
at 10 U.S. hospitals under the direction of NeuroRx in
collaboration with RELIEF
THERAPEUTICS Holding AG (SIX: RLF;OTCQB: RLFTF).
NeuroRx has signed an agreement to complete a business combination
with Big Rock Partners Acquisition Corporation (NASDAQ:
The clinical trial was originally approved as a 28 day study at
FDA's direction. In December, NeuroRx added a 60 day
endpoint based on the recognition that the traditional
28-day endpoint adopted in the 1990s for trials in Acute
Respiratory Distress Syndrome is not appropriate for critically ill
patients with Covid-19, who are frequently maintained in the ICU
with advanced technologies well beyond this time point. NeuroRx and
other clinical trial sponsors alerted FDA to this trend
the FDA published formal guidance2 changing the required time
for measuring the prespecified endpoint of alive and free of
respiratory failure in critically ill patients to 60 days.
Interim data are being reported because they were unblinded as per
the original protocol and the last patient in the trial reached day
60 yesterday. Therefore, study conduct cannot be adversely
influenced by release of these interim
At 28 days, patients treated with ZYESAMI demonstrate 35%
higher likelihood of recovery from respiratory failure with
continued survival compared to patients treated with placebo
(Hazard Ratio 1.53; P=.08). In tertiary care hospitals,
ZYESAMI-treated patients were 46% more likely to recover and return
home before day 28 (Hazard Ratio controlling for age and severity
1.84; P=.058). Should these trends continue through day 60, they
have the potential to reach statistical significance. At day 28, a
highly significant 10-day difference in median time to recovery and
hospital discharge has emerged in ZYESAMI-treated patients compared
to those treated with placebo (P<.006).
Should the above trends continue through day 60, NeuroRx
anticipates filing a request for Emergency Use Authorization in
this population of critically-ill patients (i.e. those on High Flow
Nasal Oxygen) who have exhausted all currently approved treatments.
FDA decisions implement a benefit/risk framework. NeuroRx
previously announced the high degree of safety observed with use of
ZYESAMI. This safety has continued to be documented in the more
than 300 additional patients treated under the Expanded Access
Protocol and in patients who have filed requests under the federal
Yesterday's guidance emphasizes the importance of analyzing
patient outcomes by treatment subgroup and, in this case, the study
did not recruit enough patients treated with mechanical ventilation
to confirm the benefit seen in open-label studies. In the seven
months that have elapsed since the trial began, mechanical
ventilation has gone from first line therapy to treatment of last
resort for patients with Covid-19. Recognizing this, NeuroRx signed
clinical trial agreements with the I-SPY clinical trial platform
and the National Institutes of Health under which ZYESAMI will
continue to be evaluated in patients who require mechanical
The study's principal investigators, Dushyantha Jayaweera,
M.D., FACP (University of Miami), Professors J. Georges Youssef,
M.D. (Houston Methodist Hospital), and Richard Lee, M.D.
(University of California, Irvine) commented, We are excited to report that ZYESAMI
demonstrates a highly significant reduction in time to recovery
compared to patients treated with placebo in those treated with
High Flow Nasal Oxygen, together with increased likelihood of
recovery and excellent safety. We look forward to learning whether
this benefit can also be shown for patients treated with other
stages of Covid-19 with inhaled forms of ZYESAMI. We look
forward to working with the sponsor to secure emergency use
authorization for ZYESAMI in this population of
Jonathan C. Javitt, M.D., M.P.H., CEO of NeuroRx, added,
forward to reporting the final 60 day efficacy data shortly. We are
indebted to the researchers, patients, and families who have helped
us demonstrate this meaningful clinical benefit for ZYESAMI. We are
honored to name the drug in honor of the late Prof. Sami Said who
discovered its active ingredient, VIP. Additional efficacy data on
patients who require mechanical ventilation will be obtained from
ongoing research supported by BARDA and the National Institutes of
Health, in addition to our newly initiated study of inhaled use
ZYESAMI in hospitalized patients who have not yet developed
2 COVID-19: Developing Drugs and Biological
Products for Treatment or Prevention.
About VIP in COVID-19
Intestinal Polypeptide (VIP) was first discovered by the late Dr.
Sami Said in 1970, for whom ZYESAMI is named. Although first
identified in the intestinal tract, VIP is now known to be produced