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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).

Inmazeb® (REGN-EB3) Ebola Treatment Description

Inmazeb® (REGN-EB3) is a novel combination of three fully-human monoclonal antibodies (mAbs): atoltivimab (REGN3470), maftivimab (REGN3479), and odesivimab (REGN3471) that target Ebola virus glycoprotein developed using VelociSuite® proprietary rapid response technologies. VelociGene enables rapid, automated, and high-scale manipulation of mouse DNA with almost no limitations on the size and sophistication of modifications. 

Regeneron Inc.'s Inmazeb's three mAbs bind to different, non-overlapping epitopes on Zaire ebolavirus glycoprotein. The mAbs combination help neutralize the Ebola virus disease (EVD) by blocking their ability to invade patients' and/or enlist other immune cells to target infected cells and remove them from the body. Inmazeb has only been evaluated for efficacy against Zaire ebolavirus.

The U.S. FDA issued approval on October 14, 2020, for Inmazeb for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including newborns of mothers who have tested positive for the infection. 

On August 19, 2022, the World Health Organization (WHO) published its first guideline for Ebola virus disease therapeutics, with new strong recommendations for the use of monoclonal antibodies, including Inmazeb.

Regeneron Pharmaceuticals, Inc. is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.

Inmazeb History

On October 14, 2020, Regeneron announced that the U.S. Food and Drug Administration (FDA) approved Inmazeb to treat infection caused by Zaire ebolavirus in adult and pediatric patients, including newborns of mothers who have tested positive for the disease. Regeneron expects to deliver an established number of treatment doses over the course of 6-years and receive compensation of approximately $10 million in 2021 and an average of $67 million per year for each of the next five years (2022-2026). Inmazeb was developed in collaboration and with federal funds from BARDA, part of the Office of the Assistant Secretary for Preparedness and Response at the HHS under ongoing USG Contract Nos. HHSO100201700016C and HHSO100201500013C. 

Inmazeb Dosage 

Inmazeb is administered as a single, weight-based intravenous infusion (50 mg atoltivimab, 50 mg maftivimab, and 50 mg odesivimab per kg).

Inmazeb Limitations

The efficacy of INMAZEB has not been established for other species of the Ebolavirus and Marburgvirus genera. Zaire ebolavirus can change over time, and factors such as the emergence of resistance or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating Zaire ebolavirus strains when deciding to use INMAZEB.

INMAZEB may reduce the efficacy of a live vaccine; therefore, avoid the concurrent administration of a live vaccine during treatment with INMAZEB.

Inmazeb Drug Interactions

The use of Inmazeb may reduce the efficacy of live vaccines. The interval between live vaccination following initiation of Inmazed therapy should be in accordance with current vaccination guidelines.

Inmazeb Adverse Events

The most common adverse events reported in at least 10% of subjects who received INMAZEB were pyrexia (or elevation in fever), chills, tachycardia, tachypnea, vomiting, hypotension, diarrhea, and hypoxia.

Inmazeb News

August 19, 2022 - The WHO's guideline development group issued a Strong Recommendation for using Inmazeb.

July 27, 2022 - CTS published: A drug-disease model for predicting survival in an Ebola outbreak. This mathematical investigation demonstrates that drug-disease modeling can be an important translational tool to integrate preclinical data from an NHP model recapitulating disease progression to guide future translation of preclinical data to clinical study design.

January 11, 2021 - Springer published: REGN-EB3: First Approval. This article summarizes the milestones in the development of REGN-EB3, leading to this first approval for the treatment of infection caused by Zaire ebolavirus (Ebola virus) in adult and pediatric patients.

December 12, 2020 - The NEJM published a study that found REGN-EB3 was superior to ZMapp in reducing mortality from EVD. 

October 14, 2020 - The U.S. Food and Drug Administration approved Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn), a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients.

July 29, 2020 - Regeneron Pharmaceuticals announced that the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, agreed to procure REGN-EB3 as part of the national preparedness for public health emergencies.

July 27, 2020 - Expanded Access Protocol for Treatment of Ebola Virus.

April 17, 2020 - The U.S. Food and Drug Administration accepted for Priority Review a new Biologics License Application (BLA) for REGN-EB3, an investigational triple antibody cocktail treatment for Ebola virus infection.

December 12, 2020 - NEJM published study: A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.

November 27, 2019 - Nearly 90 percent survival for patients who received REGN-EB3 treatment earlier in the course of their disease; 66.5 percent survival among all patients who received REGN-EB3.

November 26, 2018 - The Ministry of Health of the Democratic Republic of the Congo announced the launching of a randomized clinical trial to evaluate the effectiveness and safety of medications used in Ebola patients' treatment. 

October 3, 2017 - The US government announced it is expanding the Strategic National Stockpile supply of vaccines and medications to better prepare for an Ebola outbreak.

JYNNEOS® Mpox Smallpox Vaccine Clinical Trials, Dosage, Efficacy, Side Effects, Usage

Bavarian Nordic A/S JYNNEOS® (MVA-BN®, IMVAMUNE®, IMVANEX®), third-generation, live, attenuated vaccinia virus, Modified Vaccinia Ankara (MVA) vaccine. The MVA is cultured in chicken embryo fibroblast cells and maintained in a serum-free medium. It cannot replicate in the human body but can elicit a potent immune response. It is purified and filtered from the cells using various methods, including benzonase digestion.

Since 2003, Bavarian Nordic (BN) has co-developed JYNNEOS with the U.S. Government's Biomedical Advanced Research and Development Authority (BARDA) to ensure that adult populations can be protected from smallpox, including individuals with weakened immune systems or at high risk of adverse reactions to traditional smallpox vaccines based on replicating vaccinia virus strains. Approved by the U.S. Food and Drug Administration (FDA) in 2019, JYNNEOS was the first smallpox vaccine successfully developed under the Project BioShield initiative. BARDA has supported the development of a freeze-dried formulation of the vaccine to replenish the stockpile, and in 2017, it awarded BN a ten-year contract. BN has supplied a liquid-frozen formulation of JYNNEOS to the U.S. government for stockpiling since 2010 and in response to the mpox outbreak in 2022-2023. The U.S. government recommends two doses to provide robust protection, and routine immunization against mpox is not recommended for the general public. Booster doses (third) are recommended for specific individuals. On February 14, 2025, Interim Clinical Considerations for Use of Vaccine for Mpox Prevention in the United States stated, 'That while two vaccines can be used to prevent mpox (JYNNEOS®, ACAM2000®), only JYNNEOS has been used in the ongoing mpox outbreak.'

A meta-analysis of 16 studies published on April 26, 2024, revealed that the vaccine efficacy (VE) for one preexposure prophylactic JYNNEOS vaccination ranged from 35% to 86%, and the VE for two doses ranged from 66% to 90%. On June 6, 2025, a preprint study reported that MVA-BN vaccination induced sustained immunological memory after two-dose primary vaccination, as evidenced by a rapid anamnestic response up to five years post-vaccination. These results suggest that immunity does not wane for at least five years.

Since September 13, 2024, JYNNEOS has been commercially available in the U.S. and added to the World Health Organization (WHO) prequalification (PQ) list. The WHO PQ and Emergency Use Listing are mechanisms for evaluating the quality, safety, and efficacy of medical products, including vaccines. According to estimates from the U.S. Centers for Disease Control and Prevention (CDC), approximately two million U.S. individuals are eligible for mpox vaccination. Recent data shows that 15% of eligible people have received only one dose of the JYNNEOS vaccine. 

On June 5, 2025, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the mpox upsurge continues to meet the criteria of a public health emergency of international concern. On June 5, 2025, the WHO released new recommendations for clinical management and infection prevention and control (IPC) for mpox. This living guideline from WHO incorporates new evidence to dynamically update recommendations for clinical management and IPC for mpox infection. As of November 2025 (WHO reported #59), approximately 1 million vaccine doses (JYNNEOS®) have been administered to people across 12 African countries, and it remains available in the United States.

Bavarian Nordic A/S, headquartered in Kvistgaard, Denmark (OTCMKTS: BVNRY) (OMX: BAVA), focuses on developing, manufacturing, and commercializing life-saving vaccines. The MVA-BN® vaccine is marketed under the brand names IMVANEX® in the European Union, IMVAMUNE® in Canada, and JYNNEOS® in the U.S. JYNNEOS® is the only mpox vaccine that the WHO has prequalified. In 2025, JYNNEOS vaccine revenues increased by 51%, primarily driven by the phasing of supply and also positively impacted by supplemental payments for the freeze-dried vaccines delivered to the U.S. government, triggered under options exercised in May 2025.

JYNNEOS Vaccine Availability

As of 2025, healthcare providers in the United States can order JYNNEOS through their preferred wholesalers and distribution partners to make it available to at-risk individuals at pharmacies, physician offices, and public health clinics. This HHS operational planning guide is provided to aid state, tribal, local, and territorial health officials in their planning and response efforts. JYNNEOS  became commercially available at pharmacies in the U.S. in 2024.

IMVAMUNE® (MVA-BN) Vaccine Availability

The European Commission issued marketing authorization for smallpox prevention for MVA-BN (Imvanex) in 2013. It was extended to include mpox for adults in 2022, based on efficacy data in non-human primates and immunogenicity data from numerous studies involving more than 4,000 healthy and immunocompromised individuals. On September 19, 2024, the European Medicines Agency (EMA) recommended extending the indication of the smallpox and monkeypox vaccine Imvanex to adolescents aged 12 to 17. It is inferred that the vaccine will provide similar protection in adolescents as in adults. On November 11, 2024, the WHO confirmed that the Mpox Vaccines Access and Allocation Mechanism endorsed an independent Technical Review Committee to allocate 899,000 MVA-BN vaccine doses to nine countries across the African region. As of June 27, 2025, more than 731,000 doses of the MVA-BN vaccine have been administered in Africa. On October 31, 2025, BN announced an order for 750,000 MVA-BN vaccines to be delivered in Europe in 2026.

JYNNEOS (IMVANEX®) and 4CMenB Vaccination Program in the United Kingdom

Effective August 1, 2025, a new routine mpox and gonorrhoea vaccination (4CMenB) program, primarily for men who have sex with men at higher risk of acquiring these infections, will be delivered by local authority-commissioned sexual health services in the United Kingdom.

Bavarian Nordic JYNNEOS Production

Since 2022, Bavarian Nordic has built a vaccine inventory to provide surge capacity in the event of potential outbreaks. Bavarian Nordic has identified 50 million doses that could be supplied during the next 12-18 months, pending regulatory approvals and demand. The Company has informed the African CDC that it can manufacture an additional 10 million doses by the end of 2025, which aligns with current orders.

On December 16, 2024, Bavarian Nordic announced a license and manufacturing agreement for its MVA-BN® mpox vaccine with Serum Institute of India Pvt. Ltd. Adar Poonawalla, CEO of Serum Institute of India, said, "Partnering with Bavarian Nordic on the MVA-BN mpox vaccine reflects our shared commitment to protect millions at risk. Leveraging our manufacturing strength and rapid response capabilities, we aim to enhance epidemic preparedness and expand access to life-saving vaccines, safeguarding vulnerable populations and easing the global burden of mpox."

Bavarian Nordic - Biomedical Advanced Research and Development Authority Agreements 

Bavarian Nordic has collaborated with the U.S. government on the development, manufacturing, and supply of the mpox (smallpox) vaccine. On May 6, 2025, Bavarian Nordic announced that BARDA had exercised additional options, valued at $143.6 million, under the existing contract to supply a freeze-dried formulation of JYNNEOS smallpox vaccine. On September 24, 2024, Bavarian Nordic announced that it had received an additional order valued at $63 million from BARDA to manufacture additional bulk products and final freeze-dried doses of the JYNNEOS® smallpox/mpox vaccine. On August 8, 2024, Bavarian Nordic announced a new order valued at $156.8 million from the BARDA to manufacture additional bulk products for JYNNEOS®. On August 3, 2023, Bavarian Nordic announced it would manufacture and supply additional liquid-frozen doses of JYNNEOS to the U.S. government in 2023, valued at $3 million. Additionally, on August 3, 2023, Bavarian Nordic announced that BARDA had placed a new $120 million order, primarily for manufacturing a new bulk product for the JYNNEOS smallpox/mpox vaccine.

JYNNEOS Vaccine U.S. FDA

The U.S. Food and Drug Administration (FDA ) initially approved JYNNEOS for smallpox prevention in September 2019, based on a comprehensive development program comprising 22 clinical trials, including two Phase 3 studies. The FDA granted Bavarian Nordic a Priority Review Voucher (PRV) under the Material Threat Medical Countermeasure program, thereby accelerating the FDA's review of the application. The FDA's emergency use authorization (EUA) for JYNNEOS for mpox was issued by Peter Marks, MD, Ph.D., in Application Number 28801 on August 9, 2022. JYNNEOS' or mpox use was based on survival data from lethal mpox virus challenge studies (FDA's Rule) on human primates. The FDA granted an Emergency Use Authorization for use in adolescents in 2022. On March 15, 2023, the U.S. FDA updated JYNNEOS - STN: BL 125678/20. As of June 2025, JYNNEOS is the only FDA-approved smallpox and mpox vaccine for military and non-military use. On March 31, 2025, the FDA approved the freeze-dried formulation of JYNNEOS.

JYNNEOS Vaccine U.S. CDC

As of June 2025, the U.S. Centers for Disease Control and Prevention (CDC) recommends the JYNNEOS vaccine for specific populations, including those affected by the clade II mpox outbreak. In November 2021, the CDC Advisory Committee on Immunization Practices (ACIP) vaccine committee unanimously recommended JYNNEOS as an alternative to ACAM2000 for primary and booster doses of smallpox vaccine. The ACIP group leader, Pablo Sanchez, MD, led the presentations on the mpox vaccine on October 20, 2022, and February 22, 2023. The CDC announced Interim Clinical Considerations on February 22, 2023: Mpox vaccination should continue to be offered to people with the highest potential for exposure to mpox. An updated U.S. National Mpox Vaccination Strategy was published on February 6, 2023. 

On June 23, 2023, Agam Rao, MD, CAPT, U.S. Public Health Service, presented: Considerations for Long-term Protection against Mpox - No CDC Recommendation for a Third JYNNEOS Dose, Including Persons with Advanced HIV or Other Severe Immunocompromised Immune Systems. On August 18, 2023, the CDC stated that all adults at risk for mpox should receive the JYNNEOS vaccine, regardless of childhood smallpox vaccination status. On October 25, 2023, the CDC recommended the routine use of JYNNEOS for individuals at risk of smallpox or mpox infection. Survey results published in the U.S. CDC's Volume 30, Number 5, May 2024, showed that among vaccine-eligible GBMSM, uptake was 69% (95% CI 65%–72%; 601/875) and 92% (95% CI 89%–94%; 601/655) among those offered the JYNNEOS vaccine.

MVA-BN® Vaccine

As of October 2025, the European Commission currently approves MVA-BN for individuals aged 12 years and older. As of May 2025, the Democratic Republic of the Congo (DRC) had administered more than half a million mpox vaccine doses since October 2024, having received over 950,000 doses from various sources. The European Commission delivered 10,000 doses of the MVA-BN® vaccine to Uganda in January 2025. On September 26, 2024, Bavarian Nordic announced an agreement with UNICEF to supply 1 million doses of the MVA-BN® mpox vaccine for African countries. Under the agreement, UNICEF has negotiated a price of up to $65 per vaccine dose, the lowest on the market. On August 20, 2024, USAID confirmed that it would donate 50,000 Jynneos vaccines to the DRC. On August 13, 2024, Bavarian Nordic announced a new order from the European Health Emergency Preparedness and Response Authority (HERA) for the MVA-BN® vaccine. HERA will procure 175,420 vaccine doses for donation to the Africa Centers for Disease Control and Prevention.

Additionally, Bavarian Nordic will donate 40,000 doses to HERA. This more significant donation follows a recent pledge from the Company for 15,000 doses as part of a coordinated response in the African region by Gavi, WHO, and UNICEF. Bavarian Nordic was awarded a contract on September 13, 2023, to supply its MVA-BN smallpox vaccine to rescEU, a strategic reserve within the European Union.

MVA-BN® Vaccine For Adolescents

On October 7, 2025, BN announced topline results from a phase 2 clinical study of its MVA-BN® mpox/smallpox vaccine in children aged 2 to 11. Pending final results from the survey, the Company plans to submit the data to the European Medicines Agency in 2026 to support an extension of the vaccine's approval to include children aged 2 years and older.

As of 2025, the CDC has published updated Clinical Considerations for Mpox in Children and Adolescents in the United States.

On April 15, 2025, Dr. Buddy Creech presented the immunogenicity and safety of JYNNEOS in 12- to 17-year-olds to the U.S. CDC's Advisory Committee on Immunization Practices (ACIP). The Evidence-to-Recommendations Framework: Vaccination with Jynneos for Adolescents at Risk of Mpox During Outbreaks was presented by Faisal Syed Minhaj, PharmD, MPH. Additionally, Routine Vaccination with Jynneos for Adolescents at Risk of Mpox was discussed.

A National Institutes of Health-funded Phase 2 clinical trial of JYNNEOS in 229 adolescents found it to be. It generated an antibody response equivalent to that seen in adults—a peer-reviewed study funded by the U.K. The Health Security Agency, in a June 15, 2023, publication, concluded that a single dose of MVA–BN for post-exposure prophylaxis was well tolerated in children and induced robust antibody and cellular responses up to 15 weeks after vaccination. On September 15, 2022, the U.S. CDC confirmed that children and adolescents exposed to people with suspected or confirmed mpox infections might be eligible for post-exposure prophylaxis with vaccination. In addition, the CDC published interim Clinical guidance for Healthcare Providers in September 2022.

Bavarian Nordic announced on October 29, 2024, the initiation of a Phase 2 clinical study (NCT06549530) of the MVA-BN mpox/smallpox vaccine in children aged 2 to 11 years in the Democratic Republic of the Congo (DRC), with plans also to include sites in Uganda. The study is partially funded by the Coalition for Epidemic Preparedness Innovations, which announced on May 30, 2024, that it awarded BN $6.5 million to support phase 2 clinical trials.

MVA-BN® Vaccine For Pediatrics

On June 26, 2025, Bavarian Nordic announced the initiation of a Phase 2 clinical trial designed to support approval and use of the MVA-BN® vaccine in infants under 2 years of age. The first participants have been vaccinated in a study (NCT06844487) in Africa, evaluating the safety and immunogenicity of MVA-BN in 344 infants aged 4-24 months. Bavarian Nordic is also sponsoring a trial of MVA-BN in children aged 2-11 years. Topline results from this Phase 2 trial (NCT06549530) are anticipated in the third quarter of 2025. Both studies are part of the PregInPoxVac research project, led by the University of Antwerp and the University of Kinshasa.

JYNNEOS For Pregnant Women

Bavarian Nordic announced on June 26, 2025, the initiation of a Phase 2 clinical trial recruiting for a Phase 2 study (NCT06844500), which is planned to enroll 359 women (pregnant or breastfeeding), also to be evaluated for the safety and immunogenicity of MVA-BN, conducted in the Democratic Republic of Congo. This study is part of the PregInPoxVac research project.

The U.S. FDA says available human data on JYNNEOS administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Four developmental toxicity studies conducted in female rats and rabbits evaluated the effect of JYNNEOS on embryo-fetal and postnatal development.

JYNNEOS Vaccine HIV

The European AIDS Clinical Society recommends the vaccine for adults infected with HIV or on preexposure prophylaxis treatment, and it may support additional national recommendations for the vaccine in the future. On August 5, 2022, the early release of the CDC Report - Interim Guidance - confirmed the JYNNEOS vaccine can be safely given to people who are living with HIV infection and those who are taking preexposure prophylaxis (PrEP). HIV immunocompromised persons may have a diminished immune response to JYNNEOS.

JYNNEOS Vaccine Efficacy

On July 26, 2024, BN announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) had recommended approval of a Type II variation for the IMVANEX smallpox and mpox vaccine. BN confirmed that in real-world studies, vaccine effectiveness (VE) against mpox (clade 2) disease was demonstrated at least 14 days after vaccination, with adjusted VE estimates ranging from 35% (95% CI, -2-59) to 89% (95% CI, 76-95) after one MVA-BN dose and from 66% (95% CI, 47-78) to 90% (95% CI, 86-92) after two MVA-BN doses.

The JAMA Network published results from a study on October 3, 2024, which concluded that two doses provided 66% effectiveness and one dose provided 36% effectiveness in achieving peak immunity during the 2022 mpox outbreak. The findings of a study conducted in the context of a targeted vaccination program in Canada, published on September 11, 2024, suggested that a single dose of MVA-BN is moderately effective (58% [95% CI 31% to 75%]) at preventing clade 2 mpox infection. The study showed that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6 to 12 months. High titers of mpox NAbs (median titer 965) were detected at three months. MVA-BN provided 66% efficacy as a 2-dose regimen and 36% as a 1-dose regimen at peak immunity during the 2022 mpox outbreak in the U.S.

U.S. CDC research, published in the journal Emerging Infectious Diseases, Volume 30, Number 10—October 2024, concluded that the estimated effectiveness of the 2-dose JYNNEOS vaccine was approximately 80%. Results from a study announced in March 2024 showed mpox antibodies waned within a year of JYNNEOS vaccination. Among individuals who received childhood smallpox vaccination, most had detectable IgG antibodies one year after vaccination. The GMT reduction between 4 weeks after the last vaccine dose in 2022 and the one-year follow-up visit was 2.5-fold for those vaccinated with two doses of JYNNEOS and 1.9-fold for those vaccinated with one dose of JYNNEOS.

On March 14, 2024, the U.S. CDC staff stated, 'JYNNEOS vaccination is expected to be effective regardless of mpox clade. The Mpox virus is divided into two clades: Clade I, further divided into lineages 1–5, and Clade II, divided into subclades IIa and IIb. Clade IIb is responsible for the global mpox outbreak that began in May 2022. On December 7, 2023, the CDC published a Health Alert Network Health Advisory stating that mpox vaccines are expected to be effective for both Clade I and Clade II MPXV infections. However, the ECDC reported in 2023 that real-world data regarding JYNNEOS' effectiveness against clade 1 is lacking.

The Lancet Infectious Diseases reported on December 7, 2023, that 12% of vaccinated individuals were non-antibody responders, whereas all people with mpox infection developed a neutralizing antibody response. A case series (67) study published in The Lancet Infectious Diseases on September 4, 2023, confirmed that natural and vaccine-induced immunity are not fully protective against mpox infection. Demographic subgroup information is available in Section 1.1 of the Clinical Review Memo, which details participation in the clinical trials and notable analyses of demographic subgroup outcomes. And Section 6.2 (Postmarketing Experience) to the Package Insert.

The CDC reported in October 2023 that the JYNNEOS Vaccine's Effectiveness (VE) against mpox ranges from 36% to 75% for a single dose and 66% to 89% for a two-dose regimen. VE trended higher among immunocompetent participants than among those who self-reported as immunocompromised. The Lancet Infectious Diseases reported that the JYNNEOS vaccine showed effectiveness of 66–78%, and second mpox episodes and breakthrough infections among fully vaccinated individuals have been reported. On June 29, 2023, Original Research estimated adjusted vaccine effectiveness was 66% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose, among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1).

On May 18, 2023, the New England Journal of Medicine (NEJM) published data from Cosmos, a nationwide Epic Electronic Health Record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing mpox disease among adults who received two doses of the vaccine. The estimated adjusted vaccine effectiveness was 66% (95% confidence interval [CI], 47.4 to 78.1), and among those who received one dose, the estimated adjusted VE was 35.8% (95% CI, 22.1 to 47.1). 

JYNNEOS Vaccine Coadministration

As of 2025, the CDC says limited clinical trial data have been presented on administering the JYNNEOS vaccine simultaneously with other vaccines. 

JYNNEOS Vaccine Dosage

In the U.S., the FDA-approved regimen for JYNNEOS involves subcutaneous administration of 2 injections of 0.5 mL, 4 weeks apart. 

JYNNEOS Vaccine Booster

In June 2025, results from a preprint study confirmed durable disease protection for 5 years after three doses of JYNNEOS. On October 3, 2024, JAMA published a Research Letter concluding that data suggest protective immunity may be waning in individuals vaccinated with MVA-BN in 2022 and that booster doses may be required to maintain robust protective immunity. The U.S. CDC wrote 'Based on currently available data from the unpublished CDC study, protection after the two-dose JYNNEOS vaccine series does not wane for at least five years. Thus, booster doses are not recommended for the general population.' However, France recommends a booster dose for people vaccinated more than 2 years ago.

JYNNEOS Pre- and Post-Exposure Vaccination

The mpox vaccine can be administered as post-exposure prophylaxis (PEP) to individuals with known or presumed exposure to the Monkeypox virus (MPXV). The mpox vaccine can also be given to individuals with certain risk factors and recent experiences that may increase their likelihood of exposure to mpox. As PEP, the vaccine should be administered as soon as possible, ideally within four days of exposure; administration between 4 and 14 days after exposure may still provide some protection against mpox.

On July 29, 2024, a Phase 4 clinical study was launched to assess whether an mpox vaccine can protect people against the disease after exposure to the potentially deadly infection. A study published in January 2024 concluded that the time to PEP and the observed incubation period resulted in overestimating PEP effectiveness using a conventional method. On October 10, 2022, the WHO confirmed that post-exposure vaccination (PEPV) is recommended for close contacts with MPX cases, ideally within four days of first exposure and up to 14 days after exposure without symptoms.

JYNNEOS Cell Line

JYNNEOS (MVA-BN) vaccine utilizes Chicken Embryo Fibroblast cells to produce the vaccine. Replication-competent poxvirus strains can cause clinical infections in humans and contain infectious viruses that can be transmitted to others. However, replication-deficient poxvirus strains, including MVA, do not produce contagious viruses in humans and therefore do not cause infection. As such, replication-deficient poxvirus strains pose a substantially lower risk of adverse events than replication-competent strains. 

JYNNEOS Vaccine Myocarditis Risk

According to the U.S. CDC, myocarditis and pericarditis have occurred following either primary vaccination or revaccination with live vaccinia virus smallpox vaccines, and are a known health risk for military forces (2003). The CDC reported on October 25, 2023, that VAERS and VSD data suggest an increased risk for myocarditis or pericarditis following JYNNEOS. As with smallpox vaccination, the possibility of negligible risk cannot be excluded.

JYNNEOS Side Effects

A study funded by the European Medicines Agency (EMA) concluded in March 2025 that the MVA-BN vaccination was safe and well-tolerated. The risk of a severe allergic reaction should be weighed against the risk of smallpox or mpox. A Research Letter published on May 5, 2023, reviewed a Phase 4 clinical study of adverse events following Jynneos vaccination and found that local adverse event rates were highest following intradermal administration. The adverse event rate was highest following dose 1 of intradermal vaccination (53%) and low immunization dose 2 of subcutaneous vaccination (31%). The adverse effects of immunization included local redness, itching, and swelling following intradermal vaccination, as well as local pain, swelling, and redness following subcutaneous immunization.

Jonathan Dufimmunization, Immunization Safety Office, CDC Advisory Committee on Immunization Practices, presented JYNNEOS Vaccine Safety Monitoring During the 2022 Mpox Outbreak on February 22, 2023. According to VAERS, the number of serious adverse events reported after JYNNEOS was 26. The CDC announced on December 8, 2022, that the vaccine's safety profile was consistent with the results of pre-licensure studies. The most common adverse health events reported were nonserious, including injection site reactions. Serious adverse events were rare among adults.

Severe adverse reactions, such as those associated with replicating vaccinia virus strains, including myocarditis, encephalitis, generalized vaccinia, or eczema vaccinatum, were not observed during the Jynneos development program. The U.S. FDA reports in smallpox vaccine-naïve healthy adults, the most common (> 10%) solicited injection site reactions were pain (84.9%), redness (60.8%), swelling (51.6%), induration (45.4%), and itching (43.1%); the most common solicited systemic adverse reactions were muscle pain (42.8%), headache (34.8%), fatigue (30.4%), nausea (17.3%) and chills (10.4%).

JYNNEOS Contraindication 

According to the CDC, JYNNEOS is contraindicated in persons with allergies to any vaccine component.

JYNNEOS Immunocompromised

Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to JYNNEOS.

JYNNEOS Storage Requirement

 JYNNEOS must be safely stored at 20 degrees Celsius (20°C). 

Bavarian Nordic JYNNEOS Revenues 2025

Revenue from sales of JYNNEOS/IMVANEX/IMVAMUNE in the first quarter of 2025 was DKK 629 million (DKK 344 million), which includes revenue from ongoing contracts with the U.S. government, other governments, and organizations, as well as private markets (the U.S. and Germany). For 2025, DKK 3,000-4,000 million in revenue from JYNNEOS/IMVANEX/IMVAMUNE is still expected, of which contracts have secured DKK 2,650 million as of May 2025. The ongoing, global mpox clade 1 and 2 outbreak continues to drive a surge in demand, resulting in the guided annual revenue exceeding the communicated base level of DKK 1,500-2,000 million.

In the United States, JYNNEOS (50632-0001-03) is commercially available at clinics and pharmacies, with insurance coverage for most individuals.

JYNNEOS MVA-BN® Vaccine News

October 7, 2025 - Nina Wressnigg, Head of Clinical Development Science at CEPI, said: "Although MVA-BN has been licensed for emergency use in children in the Democratic Republic of the Congo - the worst affected country - many other countries lack this access causing children to continue to bear the brunt of the suffering, marked by severe illness and possible loss of life. These new topline data provide additional positive findings that could expand licensure to children in more countries to control the ongoing outbreak."

June 26, 2025 - Paul Chaplin, President & CEO of Bavarian Nordic, stated in a press release, "These new studies will fill the gap by providing essential data about the use of MVA-BN in infants and pregnant women

May 19, 2025 - A study reported that genomics reveals zoonotic and sustained human Mpox spread in West Africa. It was noted that hMPXV-1 emerged in humans in August 2014 in southern Rivers State and circulated undetected for three years.

May 15, 2025 - The WHO published the 52nd situation report on the multi-country mpox outbreak, with data as of May 2025. The African Region has administered more than 668,000 doses of MVA-BN vaccines across seven countries.

May 9, 2025 – Bavarian Nordic A/S announced that Public Preparedness (mpox, smallpox) revenue increased by 83% to DKK 629 million compared to the first quarter of 2024.

May 6, 2025 - Paul Chaplin, President & CEO of Bavarian Nordic, stated, "Following the recent FDA approval of the freeze-dried formulation of our smallpox/mpox vaccine, we applaud the U.S. government's steadfast commitment to improving national health security through the exercise of these options. The freeze-dried vaccine, with its improved shelf life, significantly contributes to securing the long-term availability of countermeasures to protect U.S citizens against life-threatening diseases."

March 19, 2025 - Prof. Leif Erik Sander, Director of the Department of Infectious Diseases and Critical Care Medicine at Charité and a research group leader at the Berlin Institute of Health at Charité, commented, "Our results confirm that a single dose of the vaccine provides good protection against Mpox, at least for a short time. Unfortunately, we found that people with HIV – even those taking adequate medication – are not sufficiently protected by a single dose."

December 20, 2024 - Gavi CEO Dr. Sania Nishtar: "We thank the U.S. for these donations, which substantially strengthen the global mpox response. In addition to the 500,000 doses that Gavi procured directly in September through our First Response Fund, working with our donors, we now have legal frameworks in place to facilitate a substantial volume of additional pledged doses, which we will work with our partners to ensure are rolled out as quickly as possible."

November 22, 2024 - The WHO Director-General, in agreement with the advice of the IHR Emergency Committee, has determined that the mpox upsurge continues to constitute a public health emergency of international concern.

November 15, 2024 - Paul Chaplin, President and Chief Executive Officer of Bavarian Nordic, said: "We have had a busy but highly purposeful and rewarding third quarter, during which we have worked intensively to support efforts to curb the ongoing mpox outbreak in Africa."

October 23, 2024 - A study reported a distinct clade I sequence from Sudan, suggesting local circulation of Monkeypox virus (MPXV) in Eastern Africa over the past four decades.

October 14, 2024 - The WHO approved JYNNEOS for people aged 12 to 17.

September 26, 2024 - Bavarian Nordic A/S announced an agreement with UNICEF to supply 1 million doses of the MVA-BN® mpox vaccine for African countries.

August 27, 2024 - Germany intends to donate 100,000 mpox vaccine doses to African countries.

August 16, 2024 - "Children and adolescents are disproportionately affected by mpox in the ongoing outbreak in Africa, highlighting the importance and urgency to broaden access to vaccines and therapies for this vulnerable population. We applaud the NIH for their work on this study and are pleased to report data that support the use of our vaccine in adolescents, adding to the growing pool of evidence that MVA-BN is well tolerated and able to generate a relevant immune response in adolescents and adult populations," said Paul Chapel, President and Chief Executive Officer of Bavarian Nordic.

April 2, 2024 - Brian Hujdich, Executive Director of the National Coalition for LGBTQ Health, commented: "JYNNEOS is a vital step toward ensuring equitable access to healthcare for the LGBTQ+ community and marks a significant stride in preventing the spread of mpox."

JYNNEOS Vaccine Clinical Trial

The results of a Phase 2 study, posted as a preprint on September 9, 2022, concluded that priming with either 1 or 2 doses of MVA-BN induced durable immune memory, similar to the generated by replicating smallpox vaccines. When the MVA-BN vaccine was administered as a booster to individuals who had been primed 2 years earlier with MVA-BN or an older-generation replicating smallpox vaccine, it elicited a similarly rapid and durable immune response, generally well-tolerated. One-dose priming with MVA induced a long-term B-cell memory, resulting in robust anamnestic responses following an MVA booster two years later. This suggests that a single dose may offer protection against future exposure.

The FDA approval of JYNNEOS for smallpox is based on a development program comprising 22 clinical trials, including two Phase III trials. The program enrolled 7,871 individuals aged 18 to 80 who received at least one dose of the vaccine. Approval for the monkeypox indication is based on survival data from studies conducted in non-human primates. The survival rate ranged from 80% to 100% in animals vaccinated with JYNNEOS, compared to 0% to 40% in the control group.

Upon successful completion of the current study, expected in 2021, the Company plans to submit a supplement to the BLA to extend the approval for both formulations of MVA-BN, anticipated in 2022.