Zyesami (Aviptadil) COVID-19 Therapeutic Description
Zyesami (Aviptadil) is a formulation of synthetic human Vasoactive Intestinal Peptide (VIP), which the late Dr. Sami first discovered Said in 1970, for whom ZYESAMI™ is named. Because of its lack of toxicity and low cost of manufacture compared to proprietary biologics, VIP may be uniquely attractive to those focused on global countermeasures against COVID-19, says the company.
VIP is known to target the VPAC1 receptor of the alveolar type II cell (ATII) cell and protect that cell against all manner of injuries, including smoke inhalation, exposure to stomach acid, and exposure to infectious agents. VIP prevents apoptosis, blocks cytokines, lowers TNFα levels, reverses CD4/CD8 ratio, and reduces cough and dyspnea in nonclinical and clinical studies.
Although first identified in the intestinal tract, VIP is now known to be produced throughout the body and primarily concentrated in the lungs. VIP has been shown in more than 500 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury, and inflammation, says the company.
Zyesami (Aviptadil) COVID-19 Therapeutic has received orphan drug designation from the US Food and Drug Administration in acute respiratory distress syndrome and chronic lung diseases.
The U.S. FDA has approved an expanded access protocol for the use of RLF-100 in patients with Critical COVID-19 and Respiratory Failure. RLF-100 remains an investigational drug in clinical trials. The purpose of this expanded access program is to serve patients with a life-threatening need who don’t qualify for or cannot access the FDA phase 2/3 clinical trials currently underway. Patients will be treated with 12-hour infusions of RLF-100 at ascending doses of 50/100/150 pmol/kg/hr on 3 successive days.
"The patients enrolled in our study were in the ICU, having exhausted all approved treatments for COVID-19," said Jonathan Javitt, M.D, MPH, CEO and Chairman of the Board, of NRx, in a press statement issued on June 1, 2021. "We look forward to working as quickly as possible with the FDA in hopes of providing critically ill patients with a new medicine that will increase their chances of recovery and survival, enabling them to leave the hospital and return to their families significantly sooner."
Switzerland-based RELIEF THERAPEUTICS Holding AG, a biopharmaceutical company, developed the compound RLF-100™ (aviptadil).
Radnor, PA-based NeuroRx, Inc. is developing innovative therapies for high-mortality unmet needs. NeuroRx has signed an agreement to complete a business combination with Big Rock Partners Acquisition Corporation.
Zyesami (Aviptadil) COVID-19 Therapeutic Indication
Zyesami (Aviptadil) COVID-19 Therapeutic is used to treat SARS-CoV-2 infections known to cause Respiratory Failure, which is the hallmark of Acute COVID-19, as defined by the new NIH/FDA classification. Approximately 50% of those who develop Critical COVID-19 die, despite intensive care and mechanical ventilation. Patients with Critical COVID-19 and respiratory failure, currently treated with high flow nasal oxygen, non-invasive ventilation, or mechanical ventilation, will be treated with RLF-100 (Aviptadil). The ability to deliver VIP directly to the lung via inhalation could have important therapeutic implications and potentially broaden the application of the drug to patients less severely affected with COVID-19, says the company.
Separately, the National Institutes of Health conducts a confirmatory trial that randomizes patients with COVID-19 respiratory failure to ZYESAMI vs. Veklury® (remdesivir) and placebo in a factorial design trial (NCT04843761). A second nationwide trial to determine if similar benefits may be achieved in critically ill patients with inhaled ZYESAMI™ is being conducted on the I-SPY platform, maintained by the Quantum Leap Healthcare Collaborative.
Zyesami (Aviptadil) COVID-19 Therapeutic News
June 2, 2021 – RELIEF THERAPEUTICS Holding AG, a biopharmaceutical company with its lead compound RLF-100™ (aviptadil), reported today that its collaboration partner, NRx Pharmaceuticals, Inc. has announced that it has submitted an application to the U.S. Food and Drug Administration seeking Emergency Use Authorization (EUA) for the use of aviptadil in the treatment of critical COVID-19 in patients with respiratory failure.
June 1, 2021 - NRx Pharmaceuticals announced it had 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 from respiratory failure. Consistent with previously announced top-line data, the study identified a statistically significant increase in the likelihood that patients treated with ZYESAMI™ would be alive and free of respiratory failure at 60 days, compared to those treated with placebo, and identified a significantly shorter median hospital stay. The clinical study report filed with FDA further documents statistically significant advantages for ZYESAMI™ on all major secondary endpoints.
April 26, 2021 - Dosing of the first patient in a phase 3 clinical trial of ZYESAMI (aviptadil acetate) was announced by the National Institutes of Health (NIH). Dr. Anthony Fauci elaborated on the need for new COVID-19 therapeutics and discussed this trial in a White House press briefing on April 23, 2021.
April 6, 2021 - NeuroRx, Inc. reported that Aviptadil, supplied by NeuroRx, was identified by the National Institutes of Health for inclusion in phase III clinical trial in the USA and multiple foreign countries.
March 29, 2021 - NeuroRx, Inc. reported 60-day results of the Phase 2b/3 trial of intravenously administered ZYESAMI™ (aviptadil acetate) to treat respiratory failure in critically ill patients with COVID-19, which is being developed in collaboration with Relief Therapeutics Holding AG (RLFTF). Across all patients and sites, ZYESAMI™ met the primary endpoint for a successful recovery from respiratory failure at days 28 (P = .014) and 60 (P = .013) and also demonstrated a meaningful benefit in survival (P = < .001) after controlling for ventilation status and treatment site.
March 9, 2021 - NeuroRx, Inc. and TFF Pharmaceuticals, Inc. announced that the companies have entered into a feasibility and material transfer agreement (Feasibility Agreement). Under the Feasibility Agreement, NeuroRx is delivering ZYESAMI™ (aviptadil, synthetic VIP) materials to TFF to perform feasibility formulation work and testing. This feasibility work aims to formulate and identify an optimal, long-term stable formulation of ZYESAMI™ into a dry powder form with superior aerosol properties for delivery directly to the lungs. “The work being done by the NeuroRx team with ZYESAMI on behalf of critically ill patients with COVID-19 respiratory failure is both remarkable and gratifying,” said Glenn Mattes, President & CEO of TFF Pharmaceuticals. “The potential opportunity to bring this important new therapy for patients earlier in the treatment cycle is exciting."
February 23, 2021 - NeuroRx, Inc. announced that the Phase 2b/3 trial* of ZYESAMI™ (aviptadil, previously RLF-100™) for the treatment of Respiratory Failure in critically ill patients with Covid-19 had 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. Mechanical ventilation is 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.
February 23, 2021 - Big Rock Partners Acquisition Corp. filed Form 8-K.
February 9, 2021 - NeuroRx, Inc. reported preliminary results from their Phase 2b/3 trial of ZYESAMI™ (aviptadil, previously RLF-100) in collaboration with Relief Therapeutics Holdings, AG in patients with respiratory failure due to Critical COVID-19. The study showed that patients treated with the maximal standard of care plus ZYESAMI were discharged sooner from the hospital than those treated with placebo plus maximal standard of care. If authorized for use, ZYESAMI would be the first drug indicated specifically for COVID-19 patients critically ill with respiratory failure.
January 18, 2021 - The Government of India's Subject Expert Committee (SEC) meeting examined COVID-19 related proposals under accelerated approval process made in its 140th meeting held on 18.01.2021 & 19.01.2021 at CDSCO, HQ New Delhi.
December 10, 2020 - Last update: Patients with Critical COVID-19 and respiratory failure who are ineligible for enrollment in NCT04311697, who live more than 50 miles from an existing collaborating research center, or who are already hospitalized and cannot safely be transferred to a collaborating research facility may be considered for expanded access by the sponsor. Treating physicians must complete FDA Form 3396 and receive a letter of authorization from NeuroRx, along with local IRB authorization.
January 11, 2021- NeuroRx, Relief, and Quantum Leap announce the inclusion of ZYESAMI™ (RLF-100™: aviptadil) in the I-SPY COVID-19 Trial. "We at NeuroRx, together with our partners at Relief, are honored to have been selected by Quantum Leap for inclusion in the I-SPY trials platform. This will enable us to gather data on the use of inhaled aviptadil to treat Critical COVID-19 as a complement to data on intravenous aviptadil in the phase 2b/3 trial we are just concluding. We also hope to demonstrate in a second phase 2b/3 trial that aviptadil can be given in a more convenient mode of administration and show benefit in patients who can self-administer inhaled medications," said Jonathan C. Javitt, MD, MPH, CEO and Chairman of NeuroRx.
December 30, 2020 - FDA rejects COVID-19 emergency approval. “The FDA did not agree to grant (emergency use authorization), as applied for in September,” said Jonathan Javitt, the chief executive officer of U.S.-based NeuroRx, Inc., which has partnered with Relief on aviptadil, an older drug that the companies are seeking to repurpose during the pandemic. The company is now calling the drug Zyesami in its formulation against COVID-19.
November 24, 2020 - NeuroRx and Relief announce initial successful results from expanded access use of RLF-100™ (aviptadil) in patients with Critical COVID-19 and Severe Comorbidity: 72% survival seen in ICU patients. All patients had severe comorbidities (such as organ transplant, recent heart attack, and cancer) that rendered them ineligible for the ongoing randomized, controlled phase 2b/3 trial to ascertain the safety and efficacy of RLF-100™, and all patients were deteriorating despite treatment with approved therapies for COVID-19. Of the 90 patients who have reached 28 days of follow-up, 72% survived today 28.
August 3, 2020 - According to the companies, the first report of rapid clinical recovery under emergency use was from Houston Methodist Hospital doctors.
August 2, 2020 - Critically ill COVID-19 patients recovered rapidly from respiratory failure after three days of treatment with RLF-100, a therapy granted fast-track designation in the United States, two drug companies said Sunday.
June 9, 2020 - Relief Therapeutics and NeuroRx have expanded the Phase II/III clinical trial of RLF-100 (Aviptadil) to include Covid-19 patients on ventilators, high flow oxygen, and noninvasive ventilation (CPAP).
Zyesami (Aviptadil) COVID-19 Therapeutic Clinical Trials
Zyesami (Aviptadil) COVID-19 Therapeutic continues to be tested in clinical trials.