VIP

FDA status

No drug product containing VIP or aviptadil holds an FDA application. Six Drugs@FDA queries across two field paths and both names returned NOT_FOUND on 2026-08-02, with a control query on the same field returning results — the queries are recorded in this file's header comment so the negative can be re-run rather than trusted. The openFDA `drug/label` and `other/nsde` endpoints likewise return NOT_FOUND for aviptadil: there is no marketed-product listing and no prescribing information. WHY 'not-approved' AND NOT 'investigational', because this is the close call on this record. The vocabulary reserves 'investigational' for ACTIVE development by an identifiable sponsor with registered trials. ClinicalTrials.gov returns nine studies for the term 'aviptadil' and not one is recruiting or enrolling: they are COMPLETED, TERMINATED, WITHDRAWN, NO_LONGER_AVAILABLE, or — in the case of the I-SPY COVID-19 platform trial (NCT04488081) — an ACTIVE_NOT_RECRUITING platform on which aviptadil was one of fourteen historical arms. The most recently registered aviptadil trial, a phase 3 of the inhaled product, was WITHDRAWN with an actual enrolment of zero. The original US sponsor is out: NRx Pharmaceuticals' Form 10-K for 2025 states that in December 2022 it transferred all ZYESAMI manufacturing rights and know-how to Relief Therapeutics. A corporate pipeline page is not a registered trial, and 'still in development' with no trial open is the claim this vocabulary was written to refuse. SCOPE: this field is a statement about FDA and the United States only. This record makes no claim, in either direction, about whether any national regulator outside the US has authorised a product containing aviptadil — that was not verified against a regulator's own document and is therefore left blank rather than guessed.

503A compounding

Verified by downloading fda.gov/media/94155/download with a browser user-agent and extracting the text locally on 2026-08-02: 'Vasoactive Intestinal Peptide' is the final bullet in '503A Category 1 – Bulk Drug Substances Under Evaluation' in the list updated 14 May 2026. It is not in Category 2, which contains exactly six substances (Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration), and not in Category 3. READ THE CATEGORY PRECISELY, because it is about to be sold as something it is not. Category 1 is not the 503A bulks list. VIP is NOT on the 503A bulks list; the list is codified at 21 CFR 216.23(a) and Category 1 is an interim holding pen for substances still being evaluated. What Category 1 buys is enforcement discretion under a guidance, conditional on four circumstances all being present, and FDA states it lasts only 'until the agency decides on inclusion of these substances on the 503A bulks list.' FDA has already said in a proposed rule what it intends to decide — that VIP should not be included. Being under evaluation is not an approval, an endorsement, or a safety finding, and this is the one compound on this site where that sentence does the most work.

Evidence

The tier reads more generously than this record supports, so read the note rather than the badge. 'Promising-but-unproven' is assigned only because human ADMINISTRATION data exists at scale — the vocabulary reserves this tier for programmes with a human signal that were tested and not established, explicitly including ones that failed. This is one that failed, and was stopped for futility by its own monitoring board. ADMINISTRATION CHECK RUN, NOT ASSUMED, and it matters more here than almost anywhere on this site, because VIP is an endogenous human peptide and most of its literature measures it rather than gives it. NCT06729606 was opened through the ClinicalTrials.gov API on 2026-08-02: official title 'A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With Acute Respiratory Distress Syndrome Associated With COVID-19 (Trial H1: Aviptadil)'; lead sponsor National Institute of Allergy and Infectious Diseases (NIAID); phase 3; allocation RANDOMIZED, parallel, TRIPLE-masked (participant, care provider, investigator); arms 'Aviptadil + SOC' (experimental) and 'Placebo + SOC' (placebo comparator); interventions typed BIOLOGICAL 'Aviptadil', administered by intravenous infusion, and BIOLOGICAL 'Aviptadil Placebo', described as commercially available 0.9% sodium chloride solution; enrolment 471 ACTUAL; status COMPLETED (start 2021-04-20 ACTUAL, primary completion 2022-08-22 ACTUAL, completion 2022-11-20 ACTUAL); results first posted 2025-10-09; hasResults true. VIP was given to people. It was not measured as a biomarker. WHAT THE TRIAL FOUND. Per the published report, 473 participants were enrolled and 471 randomly assigned in the aviptadil comparison, with a modified intention-to-treat population of 461 (231 aviptadil, 230 matched placebo). The odds ratio for being in a better category of the primary ordinal endpoint at day 90 was 1.11 (95% CI 0.80-1.55; p=0.54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died; the cumulative percentage was 38% versus 36% (hazard ratio 1.04, 95% CI 0.77-1.41; p=0.78). The report states: 'The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility.' SCOPE, WHICH IS THE WHOLE POINT. This evidence is intravenous aviptadil in critically ill adults with COVID-19-associated hypoxaemic respiratory failure. It says nothing about the product VIP is actually sold as — a compounded intranasal spray for 'chronic inflammatory response syndrome'. On that use FDA reported it located exactly one published study, which it said failed to clearly establish benefits. A large negative trial by one route in one population is not evidence for a different route in a different population, in either direction.

What FDA found

FDA’s own words. These are the most citable thing on this site, and the least likely to appear anywhere funded by someone selling the compound.

• FDA proposed not to place VIP on the 503A bulks list, finding that its physiochemical characteristics, safety, effectiveness and historical use weigh against inclusion. The Pharmacy Compounding Advisory Committee voted the same way at its meeting on 3 November 2016.

  A PROPOSED rule, and after seven years still only proposed — which is why VIP is simultaneously a substance FDA has said it intends to exclude and a substance compounders may use under enforcement discretion. Both halves are true at once, and sites quoting either half alone get VIP wrong in opposite directions. Verified as still-not-final two ways on 2026-08-02: a Federal Register API search for documents of type RULE from FDA mentioning 'bulk drug substances' and '503A' published on or after 2019-09-06 returns a count of zero; and FDA's own bulks page, current as of 2026-05-14, still states of this proposal 'After considering public comments, the agency will issue a final regulation.' Worth setting beside the July 2026 PCAC story on this site: there the committee voted AGAINST FDA staff on six of seven peptides. Here the committee voted WITH staff, in 2016, and a decade later nothing has been codified either way. A committee vote in either direction is not a rule.

  Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

  “On balance, the physiochemical characteristics, safety, effectiveness, and historical use of VIP weigh against inclusion of this substance on the 503A Bulks List. FDA proposed to the PCAC that this substance not be included on the 503A Bulks List. At its meeting on November 3, 2016, the PCAC voted not to include VIP on the list. … The proposed rule would not place VIP on the 503A Bulks List.”

  Checked against the source on 2 August 2026.

• FDA is not taking action against compounders for using Category 1 substances. FDA states that substances in Category 1 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, and that FDA does not intend to take action against a compounder for compounding drugs using them provided the conditions in the guidance document are met.

  This is the finding that genuinely separates VIP from every peptide this site was built to cover, and it is the one most likely to be quoted without its second half. 'Does not intend to take action' is a statement of enforcement intent in a nonbinding guidance. It is not approval, it is not a determination that the substance is safe or effective, and it does not make a compounded VIP product an approved drug. FDA attaches an explicit end date to it on the same page: substances in category 1 'may continue to be within the scope of the interim enforcement policy described in FDA's guidance until the agency decides on inclusion of these substances on the 503A bulks list or unless the agency removes the substances from category 1 based on, for example, information about safety risks.' FDA has already published what it proposes to decide.

  Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act — FDA, 14 May 2026

  “Category 1 – These 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. FDA does not intend to take action against a compounder for compounding drugs using bulk drug substances listed in category 1, provided that the conditions described in the guidance document are met.”

  Checked against the source on 2 August 2026.

• The enforcement policy is conditional on all four of FDA's stated circumstances being present: the substance appears in 503A Category 1; the original and all subsequent manufacturers of the bulk drug substance are registered under section 510; the substance is accompanied by a valid certificate of analysis; and the compounded drug product complies with all other conditions of section 503A.

  Recorded in full because the conditions are where the discretion actually lives, and because they are load-bearing for a consumer. The policy attaches to compounding by a state-licensed pharmacy, a federal facility or a licensed physician — not to a vial bought from a research-chemical site, which satisfies none of these circumstances. Note condition (2): every manufacturer in the chain must be FDA-registered under section 510, which is a fact about a supply chain the purchaser cannot see. FDA also states in this guidance that products compounded from substances nominated on or after the guidance's publication date of 7 January 2025 are outside the policy entirely. The guidance is headed, on every page, 'Contains Nonbinding Recommendations'.

  Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry — FDA, 7 January 2025

  “However, at this time, until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list, FDA 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 that is not a component of an FDA-approved drug product, the subject of an applicable USP or NF monograph, or on the 503A bulks list codified at 21 CFR 216.23(a), if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website …; (2) The original manufacturer and all subsequent manufacturers of the bulk drug substance are establishments that are registered under section 510 …; (3) The bulk drug substance is accompanied by a valid COA; and (4) The drug product compounded using the bulk drug substance is compounded in compliance with all other conditions of section 503A of the FD&C Act.”

  Checked against the source on 2 August 2026.

• On effectiveness, FDA reported that it located only one published study of VIP in a condition that appears to be related to 'chronic inflammatory response syndrome' (CIRS), and that the study failed to clearly establish benefits of the administration of VIP.

  Directly on point for the use VIP is actually sold for, which no other finding on this record reaches. The single study FDA located is listed in the proposed rule's reference list as Shoemaker, R.C., et al., 'Vasoactive Intestinal Polypeptide (VIP) Corrects Chronic Inflammatory Response Syndrome (CIRS) Acquired Following Exposure to Water-Damaged Buildings', Health, 5:396-401, 2013. FDA also recorded, in its own footnote, what it could establish about the condition itself: 'CIRS is a term we located in three publications. It appears to be the subject of research. It is not listed in the International Statistical Classification of Diseases and Related Health Problems (ICD-10), a medical classification list by the World Health Organization. Further, CIRS is not listed in the Medical Dictionary for Regulatory Activities (MedDRA).' Read that as what it is — a finding about the classification status of a term, not a verdict on whether patients are unwell.

  Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

  “Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP.”

  Checked against the source on 2 August 2026.

• FDA stated that VIP is well characterized physically and chemically, but that absent sufficient controls on its production, synthesis is likely to result in peptides of different lengths or different amino acid sequencing.

  A more interesting finding than it looks, and it cuts against a defence the market makes on VIP's behalf. Unlike BPC-157, which FDA considers not well-characterized, VIP the molecule is well-characterized — FDA says so. The concern is not the molecule, it is the MANUFACTURE: without controls on synthesis, what comes out is likely to be peptides of the wrong length or the wrong sequence. That is a risk carried entirely by the supplier, and it is the reason condition (2) of the enforcement policy is about section 510 registration of every manufacturer in the chain rather than about the peptide.

  Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

  “VIP is well characterized physically and chemically, but absent sufficient controls on its production, synthesis is likely to result in peptides of different lengths or different amino acid sequencing.”

  Checked against the source on 2 August 2026.

• FDA stated it did not find sufficient information to determine the historical use of VIP in compounded drug products, while noting that it appears VIP is currently used in compounded nasal sprays.

  Historical use in compounding is one of the four statutory criteria FDA weighs for the 503A bulks list, and on VIP it produced a blank rather than a positive. FDA is recording both halves at once: it could not document a history of use, and it could see the product being sold. The 'long history of compounding' framing used in VIP marketing is therefore not something FDA found — it is something FDA looked for and did not find.

  Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

  “We did not find sufficient information to determine the historical use of VIP in compounded drug products. However, it appears that VIP is currently used in compounded nasal sprays.”

  Checked against the source on 2 August 2026.

Documented safety signals

• FDA stated that although most adverse reactions observed related to the use of VIP appear to be relatively mild, VIP has been associated with severe immunologic reactions.

  The whole sentence, both clauses, because each half is quoted alone by a different audience. FDA is not describing VIP as broadly dangerous, and it is not describing it as benign. This sits alongside FDA's synthesis finding above: a peptide that may be produced with the wrong length or sequence, given by a mucosal route, is the standard setup for an immunologic reaction, and no immunogenicity study of a compounded VIP product is identified anywhere in the proposed rule.

  Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

  “Although most adverse reactions observed related to the use of VIP appear to be relatively mild, it has been associated with severe immunologic reactions.”

  Checked against the source on 2 August 2026.

• In the TESICO trial, the primary safety outcome — death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 — occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group, an odds ratio of 1.40 (95% CI 0.94-2.08; p=0.10).

  Read this as the trial reported it and not as a headline in either direction. The confidence interval crosses 1, so the difference is not statistically significant; the point estimate is nonetheless numerically higher in the aviptadil group, and the trial was stopped for futility rather than for harm. The population is the other constraint: 94% of participants were in an intensive care unit at baseline and roughly two in five were on invasive mechanical ventilation, so these event rates describe critical illness, not a tolerability profile that transfers to anyone else. What the trial does establish is that a safety database of this size and quality exists for intravenous aviptadil in this population and for no other use of VIP.

  Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial — Lancet Respiratory Medicine 2023;11(9):791-803 — PubMed, 19 June 2023

  “The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10).”

  Checked against the source on 2 August 2026.

Questions people actually ask

Every answer cites the document behind it. Where the honest answer is “nobody knows”, that is the answer you will get.

Is VIP FDA-approved?

No. No drug product containing vasoactive intestinal peptide — or aviptadil, the same molecule under its International Nonproprietary Name — holds an FDA application. Queried on 2 August 2026, FDA's Drugs@FDA database returns 'No matches found' for both names, across both the generic-name field and the active-ingredient field, and for truncated wildcard forms of both. The same field queried for a control substance returns results, so the empty answer is a fact about the database rather than an artifact of the query — a distinction that matters, because a badly-scoped search of this same database produced a false 'not in Drugs@FDA' claim about a different peptide. FDA's product-labeling and marketed-product endpoints likewise return no aviptadil record, meaning there is no FDA-approved prescribing information for it and therefore no approved indication, no approved route and no approved population.

Drugs@FDA — openFDA drug/drugsfda query for AVIPTADIL (no matching applications) — FDA, 31 July 2026

“{"error":{"code":"NOT_FOUND","message":"No matches found!"}}”

Checked against the source on 2 August 2026.

Can a compounding pharmacy legally make VIP nasal spray in 2026?

VIP is not on FDA's 503A bulks list, but it sits in Category 1 of FDA's interim policy, and FDA has stated it does not intend to take action against a compounder using a Category 1 substance if four circumstances are ALL present. FDA's words: it does not intend to take action against 'a State-licensed pharmacy, Federal facility, or licensed physician' where (1) the bulk drug substance appears in 503A Category 1 on FDA's website; (2) the original manufacturer and all subsequent manufacturers of the substance are registered under section 510; (3) the substance is accompanied by a valid certificate of analysis; and (4) the compounded product complies with all other conditions of section 503A. Three things follow that the marketing tends to drop. This is enforcement discretion in a guidance headed 'Contains Nonbinding Recommendations', not a finding that VIP is safe or effective and not an approval. It is temporary by its own terms — FDA says it runs 'until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list', and FDA has already proposed a rule that would exclude VIP. And it reaches only compounding by a licensed pharmacy, federal facility or physician; a vial bought from a research-chemical seller satisfies none of the four circumstances.

Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act — Guidance for Industry — FDA, 7 January 2025

“However, at this time, until a substance has been evaluated and is identified in a final rule as being included or not included on the 503A bulks list, FDA 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 … if all of the following circumstances are present: (1) The bulk drug substance appears in 503A Category 1 on FDA's website …; (2) The original manufacturer and all subsequent manufacturers of the bulk drug substance are establishments that are registered under section 510 …; (3) The bulk drug substance is accompanied by a valid COA; and (4) The drug product compounded using the bulk drug substance is compounded in compliance with all other conditions of section 503A of the FD&C Act.”

Checked against the source on 2 August 2026.

Is there evidence that VIP nasal spray works for CIRS or mold illness?

Not on the record FDA compiled. In its proposed rule of 5 September 2019, FDA evaluated VIP specifically for 'a condition described as "chronic inflammatory response syndrome" (CIRS)' and reported: 'Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP.' The study FDA located is listed in the rule's references as Shoemaker et al., Health, 5:396-401, 2013. FDA separately recorded what it could establish about the term itself: 'CIRS is a term we located in three publications. It appears to be the subject of research. It is not listed in the International Statistical Classification of Diseases and Related Health Problems (ICD-10) … Further, CIRS is not listed in the Medical Dictionary for Regulatory Activities (MedDRA).' Two cautions on reading that. It is a finding about how a term is classified, not a statement that the patients are well. And FDA's own conclusion was a conclusion about a compounding list, not about any individual: on balance, it wrote, the physiochemical characteristics, safety, effectiveness and historical use of VIP 'weigh against inclusion of this substance on the 503A Bulks List.'

Amendments to the List of Bulk Drug Substances That Can Be Used to Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act (proposed rule, 84 FR 46688) — FDA, 5 September 2019

“Regarding effectiveness, we located only one published study of VIP in a condition that appears to be related to CIRS, which failed to clearly establish benefits of the administration of VIP.”

Checked against the source on 2 August 2026.

Did aviptadil (Zyesami) work for COVID-19?

No. TESICO, a randomised, placebo-controlled phase 3 trial sponsored by the US National Institute of Allergy and Infectious Diseases at 28 US sites, tested intravenous aviptadil against matched placebo in adults with COVID-19-associated acute hypoxaemic respiratory failure, and its published conclusion is that 'aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo.' The trial randomised 471 participants in the aviptadil comparison, with 461 in the modified intention-to-treat population. The odds ratio for a better category on the primary ordinal endpoint at day 90 was 1.11 (95% CI 0.80-1.55; p=0.54). Deaths up to day 90 were 86 of 231 in the aviptadil group and 83 of 230 on placebo — 38% versus 36% (hazard ratio 1.04, 95% CI 0.77-1.41; p=0.78). The trial did not run to its planned end: 'The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility.' This is the largest and most rigorous human evidence that exists for VIP by any route, and it is negative.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial — Lancet Respiratory Medicine 2023;11(9):791-803 — PubMed, 19 June 2023

“The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. … Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo.”

Checked against the source on 2 August 2026.

Did FDA ever authorise Zyesami (aviptadil) for emergency use during COVID-19?

No emergency use authorization for aviptadil was issued, and no aviptadil application appears in Drugs@FDA. Be careful about the sourcing here, because it is weaker than everything else on this page: FDA does not publish EUA denial letters, so there is no primary FDA document recording the decision, and the account below is the sponsor's own. NRx Pharmaceuticals told the SEC, in its annual report on Form 10-K for 2022, that a loss of contractual milestones was caused in part by 'the FDA's November decision not to approve EUA for ZYESAMI'. The company separately announced a second declined request in July 2022 and a declined Breakthrough Therapy Designation request; those two are carried only by company press releases and are not established by the filing cited here. What is independently checkable is the outcome rather than the correspondence: aviptadil holds no FDA application, has no FDA-approved labeling, and the NIH phase 3 trial that ran alongside these requests was stopped for futility.

NRx Pharmaceuticals, Inc. — Annual Report on Form 10-K for the year ended December 31, 2022 — U.S. Securities and Exchange Commission (EDGAR), 31 March 2023

“The gains primarily resulted from not achieving the Earnout Cash milestones by December 31, 2022 due to changes to the anticipated re-start date of the NRX-101 Phase III clinical trial, slower enrollment in the NIH's ZYESAMI clinical trial, and the FDA's November decision not to approve EUA for ZYESAMI.”

Checked against the source on 2 August 2026.

Is aviptadil still being studied in clinical trials?

Not in any trial that is open. Searched on 2 August 2026, ClinicalTrials.gov returns nine studies for the term 'aviptadil', and none is recruiting or enrolling: they are completed, terminated, withdrawn, no-longer-available, or — for the I-SPY COVID-19 platform trial — an active-not-recruiting platform on which aviptadil was one of fourteen historical arms. The most recently registered aviptadil trial, AVICOVID-3 (NCT05137795), a phase 3 study of the inhaled product first posted on 30 November 2021, is recorded as WITHDRAWN with an actual enrolment of zero and a stated reason of 'Sponsor decision'; its registration was last updated on 14 May 2026. The original US developer has also exited: NRx Pharmaceuticals' Form 10-K for 2025 states that in December 2022 it transferred all ZYESAMI manufacturing rights and know-how to Relief Therapeutics. Corporate pipeline pages continue to list aviptadil, but a pipeline listing is not a registered trial, and there is no registered trial.

Inhaled ZYESAMI (Aviptadil Acetate) for the Treatment of Severe COVID-19 (AVICOVID-3) — ClinicalTrials.gov registration — ClinicalTrials.gov, 14 May 2026

“Sponsor decision”

Checked against the source on 2 August 2026.