Zyesami (Aviptadil) Therapeutic Description 2022
Zyesami® (Aviptadil, RLF-100) is a formulation of synthetic human Vasoactive Intestinal Peptide (VIP), which was first discovered in 1970. VIP is known to target the VPAC1 receptor of the alveolar type II (ATII) cell and protect that cell against all manner of injuries, including smoke inhalation, exposure to stomach acid, and exposure to infectious agents. In addition, 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 produced throughout the body, primarily concentrated in the lungs. In addition, VIP has been shown in more than hundreds of 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.
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.
NRx Pharmaceuticals was the first to formulate aviptadil for human intravenous and inhaled use under the "Good Manufacturing Practices" standards in 2020. Zyesami (Aviptadil) (RLF-100) COVID-19 therapeutic has received orphan drug designation from the U.S. Food and Drug Administration (FDA) in acute respiratory distress syndrome, chronic lung diseases, and the treatment of sarcoidosis. In June 2020, the FDA awarded Fast Track Designation to NRx for the use of aviptadil for the treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome associated with COVID-19.
Additionally, the U.S. FDA has approved an expanded access protocol for RLF-100 in patients with Critical COVID-19 and Respiratory Failure. Those respiratory conditions include Acute Respiratory Distress Syndrome, Chronic Obstructive Pulmonary Disease, acute smoke inhalation, sarcoidosis, and checkpoint inhibitor pneumonitis. On Jan. 18, 2022, the Company expanded its Right to Try programs. On Jan. 18, 2022, NRx expanded programs enabling patients with respiratory failure from COVID-19, who have tried all approved medicines, including remdesivir, and who cannot participate in a clinical study, to receive ZYESAMI upon a physician's prescription. NRx Pharmaceuticals announced on Jan. 26, 2022, a first safety report from the hospital indicated that of the first 19 patients treated by Dec. 31, 2021, three had died and 16 (84%) were reported to be alive by Jan. 22, 2021. This data regarding patients treated under the U.S. FDA's Right to Try law does not involve a control group and are not part of a research study designed to test efficacy.
The Company confirmed on Dec. 29, 2021; it filed a Breakthrough Therapy Designation request after the FDA requested clinical data on ZYESAMI® vs. Remdesivir in high-risk patients. Patients treated with ZYESAMI vs. placebo demonstrated a statistically significant (P=.03) 2.8-fold increased odds of being alive and free of respiratory failure at day 28 and day 60; A highly significant (P=.006) four-fold increased odds of survival is seen in these patients; Patients at the highest risk - those on ventilators at time of randomization - demonstrated a 10-fold increased odds of survival (P=.03).
Aviptadil [USAN:INN:BAN]; RN: 40077-57-4; UNII: A67JUW790C; InChIKey: VBUWHHLIZKOSMS-RIWXPGAOSA-N; ChemSpider ID: 17288959; ChEMBL Id: 2106041
Switzerland-based RELIEF THERAPEUTICS Holding AG, a biopharmaceutical company, developed the compound RLF-100™ (aviptadil). 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.
Radnor, PA-based NeuroRx, Inc. (Nasdaq: NRXP) 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 Indication
Zyesami (Aviptadil) COVID-19 Therapeutic is used to treat 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, noninvasive 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 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). In addition, 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 Dosage
Phase 2b/3 study Intervention: 3 successive 12-hour intravenous infusions of Aviptadil at 50/100/150 pmol/kg/hr.
Zyesami Side Effects
No unexpected side effects were identified as of February 9, 2021. 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. In addition, after a Review of 232 Enrolled Patients in ACTIV-3b Critical Care Study, No New Safety Concerns Raised by Independent Data Safety Monitoring Board as of September 29, 2021.
On October 14, 2021, a peer-reviewed study found no unexpected drug-related Serious Adverse Events (SAEs) were recorded. Hypotension was seen in two patients that were successfully managed, and treatment with aviptadil was continued. Diarrhea was observed in 4 aviptadil-treated patients compared to three control patients (19% vs. 10%; p=0.2). These adverse events are congruent with those seen in the Phase 2b/3 randomized clinical trial of aviptadil in Critical COVID-19 patients.
VAERS is a passive reporting system, meaning it relies on individuals to send in reports of their experiences. Anyone can submit a report to VAERS, including parents and patients. Furthermore, healthcare providers are required by law to report to VAERS.
Zyesami Production
NRx confirmed on August 16, 2021, the development of the first shelf-stable formulation of ZYESAMI, which was announced in early Q3'21, along with engagement in scaling up aviptadil drug substance from 100,000 doses per manufacturing batch to a projected three million doses per batch, combined with a 90% reduction in cost per gram of aviptadil drug substance.
On November 11, 2021, the Company confirmed the FDA responded to NRx's October 8, 2021, submission of updated manufacturing information for ZYESAMI® (aviptadil). The completion of this review, without the imposition of any clinical hold by the FDA, enables NRx to distribute ZYESAMI, produced at a commercial scale, under Good Manufacturing Practices for clinical trials and other future purposes approved in future regulatory actions. NRx looks forward to working with the FDA to complete the chemistry, manufacturing, and controls review that will ultimately be required for any potential drug approval.
Zyesami Availability
NRx confirmed on January 18, 2022, that it will continue to provide ZYESAMI to hospitals enrolled in NRx's Expanded Access Protocol under U.S. FDA guidelines. And NRx is also making ZYESAMI available as an investigational medicine under the Federal Right to Try Act. NRx finalized and announced its logistics and drug distribution contract with Cardinal Health, Inc., and a drug launch and commercialization support agreement with IQVIA, Inc. Cardinal Health Specialty Pharmaceutical Distribution will serve as the exclusive distributor for ZYESAMI. Cardinal Health services more than 90% of hospitals in the USA.
Nasal Spray Sentinox
The Company reported positive interim results from its clinical trial of nasal spray Sentinox in SARS-CoV-2 infected patients, confirming its safety and tolerability. Relief also reported that data from the study suggest that Sentinox could effectively reduce the SARS-CoV-2 viral load at the level of the nasal mucosa.
NRx Pharmaceuticals Financial News (Nasdaq: NRXP)
April 5, 2022 - RELIEF THERAPEUTICS Holding SA reported that it has entered into a stipulation to stay the proceedings in its pending litigation with NeuroRx, Inc. and Jonathan Javitt to allow the parties to attempt to seek to mediate their dispute.
March 31, 2022 - Net loss for the year ended December 31, 2021, was $93.1 million, or $1.98 per share, compared with a net loss of $51.8 million, or $1.51 per share for the year ended December 31, 2020.
March 8, 2022 - The Company announced that Jonathan Javitt, MD, MPH, has retired as CEO immediately. The Board of Directors appointed Robert Besthof as Interim CEO.
February 2, 2022 - NRx announced that it closed its previously announced private placement. - NRx Pharmaceuticals announced that it has entered into definitive agreements with investors to purchase 7,824,727 shares of common stock in a private placement priced at a premium to market under Nasdaq rules. The purchase price for one share of common stock and one investment option to purchase one share of common stock is $3.195. The investment options have an exercise price of $3.07 per share.
December 15, 2021 - NRx Pharmaceuticals announced that Nasdaq added the Company to the Nasdaq Biotechnology Index effective December 20, 2021.
November 16, 2021 - NRx Pharmaceuticals provided financial results for the quarter ended September 30, 2021. NRx completed a $30 million private placement in August by selling 2,727,273 shares of common stock and Preferred Investment Options. Net loss for the three months ended September 30, 2021, was $20.8 million, or $0.40 per share, compared with a net loss of $5.2 million, or $0.15 per share, for the three months ended September 30, 2020.
Zyesami (Aviptadil) Therapeutic News For 2021 - 2022
July 1, 2022 - NRx Pharmaceuticals announced the U.S. FDA declined to issue emergency use authorization for Zyesami for a sub-group of patients with critical Covid-19.
June 10, 2022 - NRx Pharmaceuticals, Inc. announced that the U.S. FDA denied the Breakthrough Therapy designation request for ZYESAMI®.
April 22, 2022 - RELIEF THERAPEUTICS Holding SA reported that NRx Pharmaceuticals, Inc. announced that it filed a new Breakthrough Therapy Designation request with the U.S. FDA. The request was based on a post-hoc analysis focused on a subgroup of patients with Critical COVID-19 that, in addition to aviptadil or placebo, were also treated with remdesivir and whose respiratory failure due to Critical COVID-19 continued to progress. NRx also reported that the request includes cumulative safety data on approximately 750 patients treated with intravenous aviptadil for Critical COVID-19.
April 1, 2022 - RELIEF THERAPEUTICS Holding SA reported today that the Swiss Patent Office IPI had issued a patent WO2020/225246 entitled, "Vasoactive Intestinal Peptide (VIP) for the Use in the Treatment of Drug-induced Pneumonitis," to Relief's subsidiary, AdVita Lifescience GmbH. The patent will provide intellectual property protection for RLF-100(R) (aviptadil) 's inhaled formulation into 2039.
March 31, 2022 - The Company confirmed it is now geographically focused primarily in the U.S. on Phase III clinical trial for which it has Fast Track and Breakthrough Therapy designation, respectively: intravenous ZYESAMI® for Critical COVID-19.
March 31, 2022 - Quantum Leap Healthcare Collaborative announced in collaboration with NRx Pharmaceuticals, Inc., that the nebulized form of ZYESAMI in the I-SPY COVID Trial of Critical COVID-19 patients had been stopped.
February 15, 2022 - The Company announced the results of a review conducted by the Therapeutics and Prevention Data Safety and Monitoring Board 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 cleared by the U.S. FDA as a Phase 3 trial that, if positive, may be used in the submission of a New Drug Application for ZYESAMI.
January 26, 2022 - NRx Pharmaceuticals announced it received a first safety report where physicians administered ZYESAMI® (Aviptadil) to patients with COVID-19 respiratory failure. The safety update report received from the hospital indicated that of the first 19 patients treated by Dec. 31, 2021, three had died and 16 (84%) were reported to be alive by Jan. 22, 2021. At the time of the report, 14 of these 16 patients had been discharged to a rehabilitation center or home and two remained in the hospital.
January 18, 2022 - NRx Pharmaceuticals announced enhancements to its Expanded Access and Right to Try programs which enable patients with respiratory failure from COVID-19, who have tried all approved medicines, including remdesivir, and who are not able to participate in a clinical study, to receive ZYESAMI® (aviptadil) upon a physician's prescription. The U.S. NIH is currently studying ZYESAMI as part of its ACTIV-3b (TESICO) trial, which has enrolled approximately two-thirds of patients and has not identified unexpected safety concerns.
January 3, 2022 - NRx announced filing a provisional composition of matter patent application with the US Patent and Trademark Office entitled "Stable, Buffer-free Compositions of Vasoactive Intestinal Peptide (VIP)." The current invention relies on specific approaches to controlling the chemical environment of VIP, an extremely delicate peptide, in order to maintain its stability without the use of such additives.
December 29, 2021 - NRx Pharmaceuticals announced that it has filed a new Breakthrough Therapy Designation request with the U.S. 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.
December 14, 2021 - NRx Pharmaceuticals provided a new safety update on ZYESAMI's third scheduled analysis. The study's Independent Data Safety Monitoring Board found no new safety concerns after reviewing a total of 348 patients and recommended continued enrollment in the study the ACTIV-3b Critical Care. This Phase 3 study is sponsored by the US National Institutes of Health and anticipates rerolling participants in Brazil during 2022.
December 9, 2021 - The Company announced Hungarian health officials have agreed on a regulatory path for Emergency Use of ZYESAMI® in the Central European region, which will start with a compassionate care program expected to begin by the end of 2021. Confirmatory demonstration of clinical effect under this program will be submitted with safety and efficacy data in support of Emergency Use Authorization in Hungary.
November 29, 2021 - NRx Pharmaceuticals announced that it has completed an analysis to identify clinical evidence from a phase 2/3 study that indicates a substantial improvement after treatment with ZYESAMI® (aviptadil) in patients with Critical COVID-19 and Respiratory Failure over existing therapies such as remdesivir. NRx to submit new analysis and safety data to the FDA in support of Emergency Use Authorization and Breakthrough Therapy Designation Requests.
November 22, 2021 - The US Food and Drug Administration denied NRx Pharmaceuticals' request for Breakthrough Therapy Designation (BTD) for ZYESAMI® (aviptadil). BTD is not required for drug approval or emergency use authorization. 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. 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.
November 16, 2021 - The Company confirmed during the 3rd quarter of 2021, NRx developed and validated a patentable formulation, manufacturing method, and container closure system that enables NRx to produce ZYESAMI (aviptadil) at a commercial scale in lot sizes of up to 100,000 doses with shelf stability of 150 days or more. And NRx is preparing a New Drug Application for ZYESAMI to be submitted under the Accelerated Approval pathway with the U.S. FDA. And the NIH has introduced ZYESAMI to E.U. and U.K. regulators via the ACTIV-3b trial.
November 11, 2021 - NRx Pharmaceuticals announced receipt of the U.S. FDA Food review that enables high volume production of ZYESAMI® (aviptadil) and shelf life extension from 62 Days to 150 Days. ZYESAMI was previously manufactured for clinical trials purposes in handmade, 300 dose batches, with a limited shelf life of 62 days.
November 8, 2021 - The Company's CEO published an update: ZYESAMI® (aviptadil) Next Steps: 'I recently received the letter below from a shareholder. The correspondence from them (taken exactly from their email) and my response regarding our next steps for ZYESAMI ® (aviptadil) can be found here.'
November 4, 2021 - NRx Pharmaceuticals announced that the U.S. FDA had declined to issue a EUA for ZYESAMI® (aviptadil). The FDA stated that it was unable to issue the EUA at this time due to insufficient data regarding the known and potential benefits of the medicine and the known and potential risks of ZYESAMI in patients suffering from Critical COVID-19 with respiratory failure. Last week, the study's Data Safety and Monitoring Board reviewed the ongoing NIH ACTIV-3b trial and found no new safety issues.
November 2, 2021 - NRx Pharmaceuticals provided a new safety update on ZYESAMI® (aviptadil). In its third scheduled analysis, the study's Independent Data Safety Monitoring Board found no new safety concerns after reviewing a total of more than 300 patients and recommended continued enrollment.
October 14, 2021 - NRx Pharmaceuticals announced the publication in the Journal of Infectious Diseases and Treatment peer-reviewed study results from a prospective, open-label, administratively controlled trial of aviptadil for the treatment of respiratory failure in patients with Critical COVID-19. The study reported 60-day survival in 81% of those treated with aviptadil, compared to 21% survival among those who received standard of care treatment at the Houston Methodist Hospital. A similar 9-fold advantage was seen in the cumulative probability of recovery from respiratory failure. Meaning - Intravenous Aviptadil demonstrated a dramatic level of efficacy that is consistent with FDA guidance for administratively controlled clinical trials and may be warranted for use in highly comorbid patients with Critical COVID-19 and respiratory failure.
October 12, 2021 - NRx Pharmaceuticals announced that a revised Investigational New Drug module on the manufacturing of ZYESAMI™ (aviptadil) was submitted to the U.S. Food and Drug Administration, containing documentation that confirmed Nephron Pharmaceuticals, Inc. is prepared to supply ZYESAMI on a commercial scale. This module will now be used as part of the FDA's rolling review process supporting the New Drug Application for ZYESAMI. NRx has also received notification that a European QP (Qualified Person) Auditor has completed an inspection at a separate manufacturing facility with no adverse findings. NRx awaits a Q.P. Declaration that is required by the E.U. regulatory authorities for the release of ZYESAMI.
September 30, 2021 - RELIEF THERAPEUTICS Holding S.A. (SIX: RLF)(OTCQB: RLFTF) reported today that the parent company of its U.S. collaboration partner, NRx Pharmaceuticals, Inc., issued a press release providing a safety update on ZYESAMI (RLF-100 / aviptadil).
September 29, 2021 - NRx Pharmaceuticals announced 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. "With this second independent safety analysis in the ACTIV-3b trial, the safety database on ZYESAMI has grown to more than 500 patients across our various clinical trials and expanded access programs. So far, there have been no reports of unexpected, drug-related serious adverse events," said Prof. Jonathan Javitt, MD, MPH, Chairman and CEO of NRx
September 27, 2021 - NRx Pharmaceuticals announced top-line data demonstrating improved outcomes at one year in highly comorbid patients with COVID-19 who were treated with ZYESAMI™. Between June and September 2020, a trial was conducted at a leading tertiary care hospital involving patients with Critical COVID-19 whose level of comorbidity excluded them from the randomized phase 2b/3 clinical trial of ZYESAMI. A statistically significant difference in both survival and recovery from respiratory failure was reported at 28 days.
September 10, 2021 - NRX Pharmaceuticals, Inc. Form S-1 (Form 8-K) relevant excerpts.
August 30, 2021 - NRx Pharmaceuticals (Nasdaq: NRXP) announced an additional finding in its phase 2b/3 clinical trial investigating ZYESAMI™ (aviptadil) for the treatment of patients with Acute Respiratory Failure due to Critical COVID-19. NRx's new analysis shows that patients treated with ZYESAMI demonstrated improved blood oxygen, indicating improved lung function, within a day of treatment. The average difference in Respiratory Distress Ratio between those treated with aviptadil and placebo was clinically meaningful and statistically significant. This latest analysis also supports NRx's application for Breakthrough Therapy Designation to the U.S. FDA for ZYESAMI.
August 24, 2021 - NRx Pharmaceuticals (Nasdaq: NRXP) announced the gross proceeds from the private placement were $30 million before deducting placement agent fees and other offering expenses.
August 19, 2021 - NRx Pharmaceuticals announced that it has entered into definitive agreements with investors to purchase common and preferred stock shares in a private placement. The gross proceeds from the private placement are expected to be approximately $30 million before deducting placement agent fees and other offering expenses. The private placement is expected to close on or about August 23, 2021, subject to the satisfaction of customary closing conditions. "The proceeds of this investment will be targeted towards accelerating the forward path of our CNS/psychiatry franchise and COVID vaccine franchises, together with supporting the transition of ZYESAMI from clinical to the commercial stage as regulatory approval is obtained from national regulators," said Jonathan C. Javitt, M.D., MPH, CEO, and Chairman of NRx Pharmaceuticals.
August 18, 2021 - NRx Pharmaceuticals provided a safety update on ZYESAMI™ (aviptadil) 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. ACTIV-3 is a randomized, blinded, placebo-controlled clinical trial testing ZYESAMI™ and the antiviral remdesivir (Veklury) in hospitalized patients with acute respiratory failure due to COVID-19 who require high-flow supplemental oxygen, delivered by nasal cannula, mechanical ventilation, or extracorporeal membrane oxygenation.
August 16, 2021 - NRx Pharmaceuticals (Nasdaq: NRXP) provided a business update and financial results for the quarter ended June 30, 2021. Primary clinical activities during the quarter centered around the analysis and regulatory filing of data from the phase 2b/3 trial of intravenous ZYESAMI™ for COVID-19 Respiratory Failure, support of the NIH-sponsored ACTIV3b Critical Care study of ZYESAMI compared to Veklury (remdesivir) alone and in combination, support of the BARDA-sponsored I-SPY trial of inhaled ZYESAMI, and the NRx-sponsored trial of inhaled ZYESAMI.
August 4, 2021 - NRx Pharmaceuticals announced it had signed an agreement with MannKind Corporation to develop a dry powder formulation of ZYESAMI™ (aviptadil), a synthetic form of human Vasoactive Intestinal Peptide (VIP), produced by the body to help protect cells against inflammatory conditions. The development will be based on MannKind's proven Technosphere® platform, which is the basis of the U.S. Food and Drug Administration-Approved Afrezza® inhaled insulin product. MannKind Corporation (Nasdaq: MNKD) focuses on developing and commercializing inhaled therapeutic products for patients with endocrine and orphan lung diseases.
July 27, 2021 - NRx Pharmaceuticals announced that the Nation of Georgia's Prime Minister and Minister of Health had issued an Emergency Use Authorization for intravenous ZYESAMI™ (aviptadil) to treat Critical COVID-19.
July 22, 2021 - NRx Pharmaceuticals Inc. said it had validated the first commercial formulation of Zyesami aviptadil for intravenous use, allowing for high volume manufacture, with an anticipated one year or greater stability, under appropriate storage conditions. The Company said it had achieved a 30-to-50-fold increase in its manufactured lot size of aviptadil, with a concurrent 90% reduction in the cost of its peptide supply.
July 19, 2021 - NRx Pharmaceuticals presented data at the Disease Control and Prevention Summit on July 21, 2021, via the following link. The presentation identifies a statistically significant effect of ZYESAMI™ (aviptadil) in preventing the sharp rise in cytokines, commonly associated with mortality in patients with COVID-19. In the recently completed phase 2b/3 trial, patients treated with placebo experienced a statistically significant elevation in interleukin 6 (IL-6) cytokine levels, whereas those treated with ZYESAMI™ had a minimal increase in IL-6. Change in cytokine level was a prespecified endpoint of the study.
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 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. Thus, 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, H.Q. 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 Clinical Trials
Zyesami (Aviptadil) COVID-19 Therapeutic continues to be tested in clinical trials.
September 29, 2021 - After Review of 232 Enrolled Patients in ACTIV-3b Critical Care Study, No New Safety Concerns Raised by Independent Data Safety Monitoring Board; ACTIV-3b Critical Care Study is Evaluating ZYESAMI™ and Remdesivir, in Critical COVID-19 Patients, as Monotherapy and in Combination Against Placebo; Study Cleared to Continue Enrollment to Target More than 600 Patients. ACTIV-3b represents one of three ongoing studies of ZYESAMI™ in Severe or Critical COVID-19.
Participants in this trial have now been followed for one year from initial enrollment. Top-line results show a statistically significant (P<.0001) 3-fold advantage in the likelihood of being alive at one year, post-treatment (60% vs. 20%) among those treated with ZYESAMI, in addition to standard of care, compared to those who received the standard of care alone. Assignment to ZYESAMI in the trial was based on the specific medical team which admitted the patient to the intensive care unit (ICU). Once in the ICU, all patients were cared for by the same medical team, and according to the same treatment protocols.
Inhaled ZYESAMI™ (Aviptadil Acetate) for the Treatment of Severe COVID-19.
Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure (COVID-AIV).
