Full Press Release Details
reports Initial Phase 2b/3 Study Results Demonstrating Significant
Benefit of ZYESAMI (aviptadil) in
Hospital Stay among Patients with Respiratory Failure due to
If Authorized for Use, ZYESAMI Would be First Treatment
Specifically for Critically Ill Patients with Respiratory
RADNOR, Pa. Feb. 9, 2021 0730 NeuroRx, Inc. today
reported preliminary results from their Phase 2b/3 trial of
ZYESAMI (aviptadil, previously RLF-100) performed in
collaboration with Relief Therapeutics Holdings, AG (SIX:RLF;
OTCQB:RLFTF) in patients with respiratory failure due to Critical
COVID-19. The study showed that patients who were treated
with the maximal standard of care plus ZYESAMI were discharged
sooner from the hospital compared to those treated with placebo
plus maximal standard of care (SOC). If authorized for use, ZYESAMI
would be the first drug indicated specifically for COVID-19
patients who are critically ill with respiratory
Javitt, M.D., M.P.H., CEO of NeuroRx, said: We are greatly
encouraged by these preliminary findings and believe they are
indicative of a biologic effect of aviptadil in hastening recovery
from Critical COVID-19. We expect to discuss with the Food and Drug
Administration and other regulatory authorities the submission of
an Emergency Use Authorization (EUA) so that ZYESAMI can be
available for treating this population that is at immediate risk of
death and for which there is no approved
the improvement in survival since the start of the pandemic,
differences in patient survival were not seen at day 28, and
patients are now being followed through day 60. The study has not
identified an overall difference in the stated primary endpoint of
recovery from respiratory failure from summary data. However,
investigators are in the process of confirming the timing of each
case of recovery from medical records, following which the
study's investigators' committee will review each case
prior to patient-level unblinding of this endpoint. Those data are
expected within a few weeks and will provide further insight into
the benefits of ZYESAMI. A blinded substudy of radiographic
improvement is similarly underway.
the secondary efficacy endpoints evaluated in patients treated with
High Flow Nasal Cannula (HFNC) therapy and with Mechanical
Ventilation, ZYESAMI showed an advantage in 15 of 16 comparisons
and demonstrated a 40% or better advantage (hazard ratio <0.7).
The likelihood of this magnitude of advantage being seen by chance
alone is about 1 in 2,000 (P=.0005). This difference includes at
least a five-day median reduction in hospital stay. (P=.043). The
largest difference observed was among those treated with HFNC who
experienced a median of 11 fewer days in hospital (15 vs.
Javitt said: The data provide preliminary support for
ZYESAMI as a drug that may help get critically-ill patients home to
their families sooner. The hospitalization data further suggest
that patients treated at an earlier stage of illness (i.e., those
who can be managed with HFNC) may have a better response to
treatment. We have launched a phase 2/3 trial to explore
ZYESAMI's inhaled use in patients who are not yet in
respiratory failure.
study of ZYESAMI's role in critical COVID-19 will be
conducted under the BARDA and DOD Medical Countermeasures-funded
Javitt added: To our knowledge this is the first
demonstration of clinically and statistically-significant benefit
by any therapeutic agent in patients with COVID-19 respiratory
failure in a randomized, double blind, prospective trial. Other
COVID-19 therapeutics have demonstrated clinical advantage in
patients with non-critical COVID-19 (ordinal scale 4 and 5) but
have not demonstrated benefit in those with Critical COVID-19
(ordinal scale 6 and 7). Steroids have demonstrated benefit in open
label studies. However, no randomized controlled trial to
date has shown efficacy when patients are in respiratory failure
and require High Flow Nasal Cannula, Non-invasive ventilation, or
Mechanical Ventilation to maintain blood oxygenation. ZYESAMI, if
authorized, would be the first drug for such critically ill
patients. Of note, the patients who received either drug or placebo
in this trial also received all approved and standard of care
treatments including Remdesivir, anti-cytokine drugs, steroids, and
Javitt added: We are forever indebted to the study
coordinators, nurses, respiratory therapists, and doctors who
carried out this study in the midst of a public health calamity
that so far has claimed the lives of nearly half a million
Americans and millions worldwide. Our study teams kept the effort
going despite contracting COVID themselves, losing family members,
and dealing with an unimaginable daily reality.
data were generated in multicenter clinical trial whose subjects
were COVID-19 patients with respiratory failure being treated with
the maximal standard of care that included anti-coagulants,
steroids, convalescent plasma and antiviral drugs. The
primary endpoint was the resolution of respiratory failure within
28 days after treatment started. The secondary endpoints were
patient survival, time to ICU discharge, time to hospital
discharge, time to return to NIAID score of 6-8, and
of 203 patients were screened and consented to participate in the
study; 136 were given ZYESAMI. while 67 received the standard of
care. All patients were evaluated through Day 28 with planned
long-term follow-up through day 60. A total of 138 patients (91
ZYESAMI, 47 SOC) survived through Day 28. Ninety-six patients (65
ZYESAMI, 31 SOC) were discharged from the hospital by Day 28. Data
analysis per protocol is ongoing.
study, conducted in 10 medical centers, also showed the safety of
the drug when administered by intravenous infusion in the ICU. No
unexpected side effects identified. The most common side effects of ZYESAMI in the
clinical trial were mild to moderate diarrhea (seen in 30% of
ZYESAMI-treated vs. 1.5% of placebo-treated patients) and systemic
hypotension (low blood pressure) seen in 31 ZYESAMI-treated
patients vs. 25 placebo patients. There were two deaths in the