Is aviptadil FDA-approved, and what does the research show?

What is aviptadil?

Aviptadil is the synthetic form of vasoactive intestinal peptide, or VIP, a peptide of 28 amino acids that the body makes itself ¹, ². VIP is classed as a neuropeptide, a signaling peptide released by nerve cells, and immune cells release it too ².

Aviptadil is not a wellness, weight-loss or performance peptide: no trial cited here tested it for any of those ¹, ⁶, ⁸, ⁹. Its largest trials gave it as an infusion into a vein to critically ill hospital patients with respiratory failure from COVID-19 ¹, ⁶. Respiratory failure there meant blood oxygen so low that patients needed high-flow oxygen, a ventilator or a machine that oxygenates blood outside the body ¹. Company documents call the drug RLF-100 and Zyesami ¹⁰, ¹¹.

Is aviptadil FDA-approved?

Aviptadil is not FDA-approved: Drugs@FDA lists no approved aviptadil product as of November 9, 2026 ³. It is an investigational drug, tested in a phase 3 trial for COVID-19 respiratory failure ¹. Investigational means still under study, and a phase 3 trial is the large, late-stage kind run to test whether a drug works. With no approved product, no FDA-approved label for aviptadil exists ³.

NRx Pharmaceuticals says in a filing with the Securities and Exchange Commission that it began developing aviptadil in partnership with Relief Therapeutics ¹¹. The company said in that filing that it asked FDA for an emergency use authorization, or EUA, on May 31, 2021 ¹¹. An EUA would have let the drug be marketed for COVID-19 ahead of an application "for formal approval," the filing says ¹¹. The company reported the outcome in these words: "In November 2021, the FDA notified us that it was unable to issue the EUA at that time due to insufficient data regarding the known and potential benefits of ZYESAMI and the known and potential risks of ZYESAMI in patients suffering from critical COVID-19 with respiratory failure" ¹¹.

The filing also reports that FDA declined a request for Breakthrough Therapy designation that month ¹¹. Breakthrough Therapy and Fast Track are FDA designations for drugs in development. The companies behind aviptadil announced a Fast Track designation in June 2020, and no approval followed ¹⁰, ³.

The filing says NRx made a narrower EUA request in February 2022, for patients at immediate risk of death despite remdesivir, an antiviral drug, and other approved treatments ¹¹. The request rested on a post-hoc analysis, the filing says, meaning one chosen after the trial's results were known ¹¹. The Pharma Letter, a trade publication, reported on July 4, 2022 that the company had announced FDA declined that request as well ¹². These are the company's accounts and a trade report of one of them; no FDA document on either decision is cited here.

ClinicalTrials.gov, the U.S. government's trial registry, gives the phase 3 trial's status as "Completed" and names the National Institute of Allergy and Infectious Diseases as sponsor ¹³. The registry records four trials of inhaled aviptadil: two terminated, one withdrawn with no participants and one completed ⁷, ¹⁴, ¹⁵. An expanded access program, under which patients unable to join a trial could be considered for the drug, is listed as "No longer available" ¹⁶. As of November 10, 2026, the registry listed no study recruiting patients to receive aviptadil ¹⁵.

A separate FDA list concerns compounding, in which a licensed pharmacy or physician makes a drug product from a bulk ingredient ⁵. FDA keeps a list of bulk drug substances nominated for compounding under section 503A of the federal drug law ⁴. The version updated May 14, 2026 places "Vasoactive Intestinal Peptide" in Category 1, "Bulk Drug Substances Under Evaluation" ⁴. The list names the peptide, not aviptadil, which is its synthetic form ⁴, ¹. No source cited here says whether the list's entry covers a product called aviptadil.

FDA's guidance says Category 1 substances "may be eligible for inclusion on the 503A bulks list, were nominated with sufficient supporting information for FDA to evaluate them, and do not appear on any other list" ⁵. The same guidance, an interim policy dated January 2025, says the agency "does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a bulk drug substance" in Category 1 ⁵. That is an enforcement policy, with conditions set out in the document, not an approval ⁵.

FDA writes that drug products compounded from nominated substances "may present particular risks when FDA has not yet completed the process to conclude whether they will be placed on the 503A bulks list" ⁵. It calls its evaluation of a nominated substance "far less rigorous and less comprehensive than the Agency's review of drugs as part of the new drug approval process" ⁵. FDA's companion list under section 503B of the same law, updated March 21, 2025, names neither VIP nor aviptadil ¹⁷.

A Welsh health-service appraisal document of June 2017, Last updated in September 2020, concerns aviptadil combined with phentolamine and names a marketing authorization holder ¹⁸.

See the FDA status of every peptide, updated weekly.

How does aviptadil work?

Aviptadil is the synthetic form of VIP, so the effects proposed for it are VIP's ¹. VIP acts through two receptors, VPAC1 and VPAC2, proteins on the cell surface that carry its signal into the cell ¹⁹, ². Both switch on adenylate cyclase, an enzyme that raises the level of the messenger molecule cyclic AMP inside the cell ¹⁹, ².

One review describes VIP as "a neurotransmitter, immune regulator, vasodilator and secretagogue" ². A vasodilator widens blood vessels, and a secretagogue prompts glands to release fluids or hormones. In the immune system VIP and its two receptors are prominent and strongly affect T cells and macrophages, two kinds of immune cell ²⁰. Signals through VPAC1 suppress T cells' migration, their multiplication and their release of cytokines, the proteins that drive inflammation ²⁰. That picture rests on laboratory work, including studies in genetically altered mice; the paper's abstract reports no trial in patients ²⁰.

For the lungs, the phase 3 trial's authors list four mechanisms shown in cells ¹. They are suppression of the virus's replication, less virus-caused cell damage, a modulated inflammatory response from monocytes, a type of white blood cell, and more surfactant ¹. Surfactant is a substance that lines the lungs' air sacs. Those are findings in cells; in patients, the same trial reported no significant improvement in clinical outcomes ¹.

Two properties shape how the drug can be given. VIP is sensitive to peptidases, enzymes that cut peptides apart, which a review calls a major obstacle to turning it into a treatment ². And because it widens blood vessels, the trial's authors treated low blood pressure as an expected effect of each infusion ¹.

What does the research show?

Studied in people: TESICO, a randomized, placebo-controlled phase 3 trial at 28 U.S. sites ¹. It randomly assigned 471 adults to aviptadil or placebo, with recovery status at day 90 as the primary outcome ¹. Randomized means chance decided who received the drug. Placebo-controlled means the comparison group received a matching saline infusion ¹.

Participants were hospitalized adults with acute hypoxemic, or low-oxygen, respiratory failure from confirmed infection with SARS-CoV-2, the virus that causes COVID-19, within four days of the failure's onset ¹. Of the 461 who received at least part of an infusion, 231 had aviptadil and 230 had placebo ¹. At the start, 94% of them were in an intensive care unit ¹. Aviptadil was infused into a vein for 12 hours a day on three days, with the dose stepped up each day ¹.

The primary outcome placed each participant, at day 90, in one of six categories ¹. They ran from at home and off oxygen for at least 77 days down to death ¹. The odds ratio for being in a better category with aviptadil than with placebo was 1.11, with a 95% confidence interval of 0.80 to 1.55 ¹. An odds ratio of 1 means no difference, and an interval that spans 1 means chance could explain the result. By day 90, 86 participants in the aviptadil group and 83 in the placebo group had died, a cumulative 38% against 36% ¹.

The paper's interpretation is that aviptadil "did not significantly improve clinical outcomes up to day 90 when compared with placebo" ¹. The trial's safety board recommended stopping the aviptadil comparison for futility on May 25, 2022, after 471 of 640 planned participants were randomized ¹. The authors reported "no evidence to suggest that aviptadil has a therapeutic role for patients with COVID-19 acute hypoxemic respiratory failure" ¹.

Two details bear on that result. Pauses and dose reductions for low blood pressure left 24% of those assigned to aviptadil without the full dose over the three days, though 97% received at least half ¹. The same trial also tested the antiviral remdesivir in 87 participants, too few for definitive conclusions, the authors say ¹.

Studied in people: an earlier randomized, placebo-controlled phase 2/3 trial of intravenous aviptadil in 203 participants with critical COVID-19 and respiratory failure ⁶. Its primary outcome was being alive and free of respiratory failure at day 28 ⁶. Phase 2/3 means a mid-stage and late-stage trial run as one.

The registry's posted results count 72 of 131 participants in the aviptadil group and 33 of 65 in the placebo group as meeting that outcome ⁶. At day 60, the registry counts 85 of 131 and 35 of 65 alive ⁶. It posts no statistical test for either comparison ⁶.

The company's filing says this trial "did not meet statistical significance for the pre-specified primary endpoint" ¹¹. TESICO's authors cite an "exploratory efficacy signal" in a "previous Phase 2/3 randomized trial" as one reason for running their larger one ¹. TESICO's authors cite that trial's published report for their "exploratory efficacy signal" ¹, ⁸.

As read on November 10, 2026, none of the registry's four inhaled-aviptadil trial records has posted results ¹⁵. One trial in severe COVID-19 enrolled 144 participants and is recorded as terminated, with no results posted ⁷. A platform trial of many drugs in critically ill COVID-19 patients, I-SPY COVID, labels its inhaled aviptadil arm closed ²¹.

A review published online in December 2011 recorded human studies of inhaled VIP in two lung conditions ². They were pulmonary arterial hypertension, high blood pressure in the lungs' arteries, and sarcoidosis, an inflammatory disease ². It reports a phase 2 trial in chronic sarcoidosis in which nebulized VIP, meaning VIP breathed in as a mist, reduced inflammatory markers in fluid washed from the lungs ². That open phase 2 trial treated 20 patients with inhaled VIP for four weeks ⁹.

The review gives no participant numbers for these studies ². None of the sources cited here reports a study of long-term use.

What are the side effects?

In TESICO, infusion reactions were significantly more common with aviptadil than with placebo ¹. "Diarrhea, facial flushing, tachycardia and hypotension occurred more frequently on aviptadil than placebo," the paper says ¹. Tachycardia is a fast heart rate, and hypotension is low blood pressure.

An infusion was paused because of an adverse event in 71 of the 231 aviptadil participants (31%) and 35 of the 230 placebo participants (15%) ¹. One was stopped for that reason in 24 (10%) and 13 (6%) ¹. On the second and third days, mean arterial pressure, an average measure of blood pressure, ran 5 to 7 mmHg lower in aviptadil than in placebo participants during each infusion ¹. It returned to parity within two hours of the infusion's end ¹. The unit mmHg, millimeters of mercury, is the standard measure of blood pressure.

The trial's main safety measure combined death, serious adverse events, organ failure, serious infection, and adverse events of the two more severe grades, through day 5 ¹. It occurred in 146 of 231 participants on aviptadil (63%) and 129 of 230 on placebo (56%) ¹. The odds ratio was 1.40, with a 95% confidence interval of 0.94 to 2.08 and a p value of 0.10, which is not statistically significant ¹. A p value estimates how readily chance alone could produce a difference this large, and 0.05 or lower is the usual threshold. Among participants not on dialysis at entry, possible serious kidney complications of low blood pressure through day 28 were similar: 41 of 213 (aviptadil) and 40 of 223 (placebo) ¹.

The authors wrote that the infusion "appeared safe in a closely monitored, largely ICU, setting in which on-treatment hypotension can be promptly addressed" ¹. Blood pressure was checked at least every two hours during each infusion and for two hours afterward ¹. The trial excluded people with refractory hypotension, severe diarrhea or end-stage liver disease from the aviptadil comparison ¹. Refractory hypotension is low blood pressure that does not respond to treatment, and end-stage liver disease is liver failure at its most advanced. It also withheld a day's infusion from anyone on a set level of blood-pressure-support drugs, or with more than three liquid stools in the previous 24 hours ¹.

In the earlier intravenous trial, the registry's non-serious adverse-event table lists diarrhea in 43 of 131 participants on aviptadil and 1 of 65 on placebo ⁶. Hypotension is listed in 34 and 14, and flushing in 13 and 2 ⁶. Deaths from any cause numbered 46 of 131 and 30 of 65, in patients who entered the trial critically ill ⁶. None of the trial sources cited here reports on aviptadil given outside a monitored hospital setting.

In sport

Aviptadil is not named on the 2026 Prohibited List of WADA, the World Anti-Doping Agency ²². The list names neither vasoactive intestinal peptide nor VIP in any section, including S2, its section on peptide hormones, growth factors, related substances and mimetics ²². Aviptadil's largest trials gave it by intravenous infusion ¹, ⁶. The list's method rule M2.2 prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ²².

Section S0 of the list reads: "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved only for veterinary use) is prohibited at all times" ²². FDA's is the only regulator's record read here, and it lists no approved aviptadil product ³. Whether S0 applies to aviptadil is a question for anti-doping bodies, and no conclusion is drawn here.

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JumpstartMD does not prescribe aviptadil. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.