Zyesami IV (aviptadil intravenous) / Relief Therap, NRx Pharma - LARVOL DELTA

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. (PubMed, Lancet Respir Med) - P3 | "Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy."

Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Relief Therapeutics Announces Positive 12-Month Stability Data for Inhaled and Intravenous Preparations of RLF-100 (Issuer Direct) - "RELIEF THERAPEUTICS...today announced positive 12-month stability data for the liquid and lyophilized preparations of RLF-100 ® , intended for intravenous (IV) and inhaled administration. RLF-100 ® is the company's proprietary, investigational formulation of aviptadil acetate....Relief Therapeutics intends to amend its previously filed provisional patent application for RLF-100 ® with the new findings. If granted, this patent could provide exclusivity for RLF-100 ® at least until 2042, without considering Hatch-Waxman extensions or other patent term adjustments. The Hatch-Waxman Act permits a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process."

Clinical data • Patent • Idiopathic Pulmonary Fibrosis

TESICO: ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=473 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | Trial completion date: Apr 2023 ➔ Nov 2022 | Trial primary completion date: Nov 2022 ➔ Aug 2022

Trial completion • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial. (PubMed, Trials) - P2 | "Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Critical care • Immune Modulation • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. (PubMed, Crit Care Med) - "The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL6

TESICO: ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=640 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Simultaneous Lung and Kidney Transplant in a Young Patient with COVID-19 (ATC 2022) - "Despite treatment with Remdesivir and dexamethasone, the patient developed hypoxemic respiratory failure with acute renal injury requiring ICU care and intubation, V-V ECMO, and dialysis. We propose that SLK transplantation should be considered for carefully selected patients with COVID-19 ARDS."

Clinical • Acute Kidney Injury • Acute Respiratory Distress Syndrome • Cough • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Solid Organ Transplantation • Transplantation

NRx Pharmaceuticals Files New Breakthrough Therapy Designation Request for ZYESAMI (aviptadil) in Subgroup of Patients with Critical COVID-19 with Respiratory Failure that were also treated with Remdesivir and continued to progress (PRNewswire) - "Breakthrough Therapy designation was requested based on data from post-hoc analysis of patients who in addition to Aviptadil or placebo were also treated with Remdesivir and whose respiratory failure due to Critical COVID-19 continued to progress....NRx Pharmaceuticals...today announced that it has filed a new Breakthrough Therapy designation request with the U.S. Food and Drug Administration (FDA) focused on a subgroup of patients with Critical COVID-19 that in addition to aviptadil or placebo were also treated with remdesivir."

Breakthrough therapy designation • Infectious Disease • Novel Coronavirus Disease

I-SPY COVID Trial Sponsored by Quantum Leap Healthcare Collaborative Suggests No Clinical Benefit with Addition of Nebulized ZYESAMI (aviptadil) When Given by Mouth Inhalation in Critically Ill Patients with COVID-19 (PRNewswire) - P3 | N=640 | ACTIV-3b (NCT04843761) | "The Data Monitoring Committee recommended concluding the open label Aviptadil arm of the I-SPY COVID Trial after 118 patients (51 on study drug and 67 on concurrent controls) were enrolled. Enrollment was stopped because the agent met the predefined futility criterion, with a greater than 90% probability that the hazard rate for recovery is less than 1.5 when compared to standard treatment (Pr(HR < 1.5) ≥ 0.9), and that the chance that the hazard rate for mortality being less than 1 is less than 50% (Pr(HRm<1.0) <0.5). The data from nebulized Aviptadil patients were compared to those from 67 patients concurrently randomized to the control arm, which included treatment with dexamethasone and remdesivir as backbone therapy....NRx previously concluded a study of intravenous Aviptadil in critically ill COVID-19 patients with positive results."

DSMB • Enrollment status • P3 data • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Submits Emergency Use Authorization Application to US Food and Drug Administration for ZYESAMI (aviptadil) to Treat Patients at Immediate Risk of Death from COVID-19 Despite Treatment with Remdesivir and Other Approved Therapies (PRNewswire) - "NRx Pharmaceuticals...announced today that it has submitted an application for Emergency Use Authorization (EUA) to the US Food and Drug Administration (FDA) for the use of ZYESAMI® (aviptadil) in patients with Critical COVID-19 who are at immediate risk of death from Respiratory Failure despite treatment with approved therapy including remdesivir and who are ineligible for enrollment into the ongoing ACTIV-3b NIH-sponsored trial."

FDA event • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces US National Institutes of Health Study of ZYESAMI (aviptadil) in Critical COVID-19 is Cleared to Complete Full Enrollment (PRNewswire) - "ACTIV-3b Trial to commence enrollment in Brazil, EU, UK, and Scandinavia in the coming months....NRx Pharmaceuticals...today announced results of a review conducted by the Therapeutics and Prevention Data Safety and Monitoring Board (DSMB) of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) on February 14, 2022. The DSMB reviewed data on 448 ICU patients with Critical COVID-19 Respiratory Failure who were enrolled in the ACTIV-3b (TESICO) trial. The TESICO protocol was submitted by NIH and cleared by the US Food and Drug Administration (FDA) as a Phase 3 trial that, if positive, may be used in the submission of a New Drug Application for ZYESAMI®."

Clinical protocol • DSMB • Enrollment closed • Novel Coronavirus Disease

Relief Receives Trademark Registration for RLF-100(R) FroRelief Receives Trademark Registration for RLF-100(R) From the U.S. Patent and Trademark Officem the U.S. Patent and Trademark Office (PharmiWeb) - "RELIEF THERAPEUTICS...announced that, on March 22, 2022, it received the certificate of registration (Reg. No. 6,674,978) for a trademark for RLF-100(R), from the United States Patent and Trademark Office ('USPTO').The trademark covers RLF-100 when used for pharmaceutical preparations and substances for the treatment of viral, metabolic, endocrine, musculoskeletal, cardiovascular, cardiopulmonary, genitourinary, sexual dysfunction, oncological, hepatological, ophthalmic, respiratory, neurological, gastrointestinal, hormonal, dermatological, psychiatric and immune system related diseases and disorders; pharmaceutical preparations for the treatment of viral diseases and; pharmaceutical preparations for the treatment of viral infections. 'Receipt of this trademark registration certificate for RLF-100, currently in late-stage development for a number of COVID-19 and non-COVID-19 related respiratory conditions.'"

Patent • Idiopathic Pulmonary Fibrosis

RECOVERY AND SURVIVAL IN COVID-19 RESPIRATORY FAILURE‚ WHEN TREATED WITH AVIPTADIL (CROI 2022) - "Multiple organ dysfunction syndrome (6.9% vs 13.8%) and respiratory failure (12.2% vs 13.8%) occurred more commonly in placebo-treated patients. Treatment with aviptadil demonstrates efficacy in improving the likelihood of recovering from respiratory failure, surviving to 60 days, and reducing hospital stay in critically ill patients with respiratory failure caused by COVID-19."

Acute Kidney Injury • Atrial Fibrillation • Cardiovascular • Critical care • Hypotension • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases

Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide. (PubMed, Crit Care Explor) - P=N/A, P2/3 | "The rapid clinical improvement seen in this patient treated with IV vasoactive intestinal peptide is consistent with the theory that vasoactive intestinal peptide protects the alveolar type II cell, ameliorates cytokine storm, and improves oxygenation in acute lung injury. This specific role of vasoactive intestinal peptide in the lung may be vital to combating the lethal effects of severe acute respiratory syndrome coronavirus 2 infection. In addition, the role of vasoactive intestinal peptide in the human maternal-fetal interface suggests that vasoactive intestinal peptide is a safe treatment of severe coronavirus disease 2019 respiratory failure during pregnancy."

Clinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

NRx Pharmaceuticals Files Breakthrough Therapy Designation Request for ZYESAMI (aviptadil) in Patients at Immediate Risk of Death from COVID-19 Despite Treatment with Remdesivir and Other Approved Therapies (PRNewswire) - "NRx Pharmaceuticals...announced today that it has filed a new Breakthrough Therapy Designation (BTD) request with the US Food and Drug Administration (FDA) focused on patients with Critical COVID-19 and respiratory failure who are at immediate risk of death despite treatment with remdesivir and other approved therapies. NRx filed the request after the FDA's request for clinical data on ZYESAMI® vs. Remdesivir in these high risk patients....Based on the FDA's input, NRx has narrowed its BTD request to treatment of COVID-19 respiratory failure in patients who progress despite treatment with remdesivir and other approved therapies."

Breakthrough therapy designation • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces Second Favorable Safety Report for ZYESAMI (aviptadil) in NIH Sponsored ACTIV-3b Critical Care Study in Patients with Life-Threatening COVID-19 (PRNewswire) - P3, N=640; ACTIV-3b (NCT04843761); "NRx Pharmaceuticals...today provided a safety update on ZYESAMI™ (aviptadil) which is being tested in the ACTIV-3b Critical Care Phase 3 study sponsored by the National Institutes of Health. In its second scheduled analysis, the study's Independent Data Safety Monitoring Board found no new safety concerns, after reviewing a total of 231 patients, and recommended continued enrollment....ACTIV-3b is a randomized, placebo-controlled trial testing ZYESAMI™ and remdesivir (Veklury) -- alone and in combination -- in hospitalized patients with acute respiratory failure due to COVID-19..."

DSMB • P3 data • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces Positive Safety Report for ZYESAMI (aviptadil) in NIH Sponsored ACTIV-3 Critical Care Study in Patients with Life-Threatening COVID-19 (PRNewswire) - P3, N=640; ACTIV-3b (NCT04843761); "NRx Pharmaceuticals (NRx) (NASDAQ: NRXP), a clinical stage, biopharmaceutical company today provided a safety update on ZYESAMI™ (aviptadil) which is being tested in the ACTIV-3 Critical Care Phase 3 study sponsored by the National Institutes of Health. The study's Data Safety Monitoring Board found no new safety concerns in the trial and recommended continued enrollment."

DSMB • P3 data • Infectious Disease • Novel Coronavirus Disease

Why NRx Pharma Stock Is Trading Higher In Mid Day Session Wednesday? (Benzinga) - "NRx Pharmaceuticals Inc shares are up around 25% during mid-day session on mild volume, in reaction to safety update on Zyesami (aviptadil) ACTIV-3 Critical Care Phase 3 study in COVID-19 patients; The NIH-sponsored trial's Data Safety Monitoring Board found no new safety concerns and recommended continued enrollment....NRXP shares are up 27.6% at $15.91 during the market session on the last check Wednesday."

P3 data • Stock price • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals and Quantum Leap Announce Treatment of Severely Ill COVID-19 Patients with ZYESAMIÔ (Aviptadil) in the I-SPY COVID Trial (PRNewswire) - "NRx Pharmaceuticals, Inc....and Quantum Leap Healthcare Collaborative™ (Quantum Leap) have begun treating patients with inhaled ZYESAMIÔ (Aviptadil), in the I-SPY COVID Trial [NCT04488081]...The I-SPY COVID Trial utilizes Quantum Leap's adaptive platform trial design methodology...In the I-SPY COVID Trial, inhaled ZYESAMI will be given to critically ill patients in order to determine whether inhaled administration has the potential to achieve similar results."

Trial status • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces Initiation of Emergency Use Training and Extension of Phase 2/3 Inhaled ZYESAMI (Aviptadil-acetate) Trial in the Nation of Georgia (GlobeNewswire) - "Physicians in Georgia and Neighboring Countries will be Trained in Emergency Use of Intravenous ZYESAMI™ Under Agreement with Local Health Authorities....It is initiating clinical training of Nation of Georgia (Georgia) ICU physicians, in the use of...inhaled ZYESAMI™ for use in phase 2/3 clinical trials, for patients suffering with COVID-19. NRx also announced that the ongoing phase 2/3 trial for the use of inhaled ZYESAMI™ has extended to Georgia, with the potential to also extend to neighboring countries in the Caucasus region, in partnership with Cromos, LLC and Denk Pharma (Georgia), operating as BriLife, LLC. NRx expects to ship clinical drug supplies to Georgia within two weeks."

Clinical • Trial status • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces Positive Data Results from ZYESAMI (Aviptadil) Expanded Access Protocol (PRNewswire) - P=NA; N=240; "NRx Pharmaceuticals...announced positive data from its ZYESAMI™ (Aviptadil) Expanded Access Protocol (EAP). Overall, patients receiving at least one dose of ZYESAMI™ in addition to intensive care were alive at 28 days....The enrollment included 240 patients dosed by March 19, 2021, of whom 196 received maximal intensive care. Fifty-six patients received palliative care (withdrawal of life support) as determined by their families and treating physicians. Among patients receiving maximal intensive (i.e. non-palliative) care, 76% of those treated with HFNC were discharged from the hospital or were alive and in the hospital at day 28, compared to 54% of those treated with mechanical ventilation."

Clinical data • Infectious Disease • Novel Coronavirus Disease

NRx Pharmaceuticals Announces Positive Results for ZYESAMI (Aviptadil-acetate) and Submits Emergency Use Authorization Application to US Food and Drug Administration to Treat Critical COVID-19 in Patients Suffering from Respiratory Failure (PRNewswire) - "NRx Pharmaceuticals...has filed an application with U.S. Food and Drug Administration (FDA) requesting Emergency Use Authorization (EUA) for ZYESAMI™ (Aviptadil-acetate), to treat Critically Ill COVID-19 patients suffering with respiratory failure....ZYESAMI™ is the first reported medicine to demonstrate increased recovery and survival in patients who have already progressed to respiratory failure....NRx previously requested limited EUA for highly co-morbid COVID-19 patients. FDA further requested randomized, prospective data regarding ZYESAMI™, which are represented in this filing."

FDA event • Infectious Disease • Novel Coronavirus Disease

Increased Recovery and Survival in Patients With COVID-19 Respiratory Failure Following Treatment with Aviptadil: Report #1 of the ZYESAMI COVID-19 Research Group - P2/3, N=196; COVID-AIV (NCT04311697); Sponsor: NeuroRx, Inc.; "Treatment with aviptadil demonstrates multi-dimensional efficacy in improving the likelihood of recovery from respiratory failure and survival to 60 days, and markedly reduced hospital stay in critically ill patients with respiratory failure caused by COVID-19."

P2/3 data • Novel Coronavirus Disease

[VIRTUAL] VIP in the Treatment of Critical COVID-19 Respiratory Failure in Patients with Severe Comorbidities (ATS 2021) - "Nineteen of 21 patients survived to day 28 in the aviptadil-treated group compared to 4 of 24 control patients (90% vs 17%; P<.0001). Kaplan-Meier analysis demonstrates a 9-fold advantage in probability of survival (Hazard Ratio 0.113; 95% CL 0.037, 0.343). A similar 9-fold advantage was seen in cumulative probability of Recovery from Respiratory Failure (Hazard ratio: 0.115; 95% CL: 0.0254, 0.5219)."

Clinical • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL6

[VIRTUAL] Rapid Recovery from COVID-19 Respiratory Failure with Comorbidity in 21 Patients Treated with Vasoactive Intestinal Peptide (ATS 2021) - "RLF-100™ (aviptadil), a synthetic form of VIP has been granted Fast Track Designation for treating Critical COVID-19 with Respiratory Failure and is currently in phase 2/3 placebo-controlled trials. Twenty of 21 patients demonstrated improvement inblood oxygenation. The improvement in patients on ECOM was similar to that seen in patients treated with conventional mechanical ventilation. Available data from blood gases showed stark increases in PaO2:FiO2 ratio after the 2nd dose (Median increase = 92.5, IQR = 74) and at 24 hours after the 3rd dose (Median increase over baseline 84.5, IQR = 110)."

Clinical • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CRP • IL6