VIP (aviptadil): what the trials show, status and safety
Summary
VIP is a messenger peptide the body makes itself; the synthetic drug substance carries the name aviptadil. As part of a fixed injectable combination it is an approved, prescription-only medicine in Germany, Denmark, Finland, France, Norway, Sweden and the United Kingdom. Its second life, as a candidate for COVID-19, ended in failure. The manufacturer's trial missed its primary endpoint, and the American regulator refused emergency use twice. The large independent trial was stopped for futility and found no difference from placebo.
Key findings at a glance
- It is an approved, prescription-only medicine in seven European countries. The European register lists national approvals for the fixed combination in Germany (number 91159.00.00), Denmark, Finland, France, Norway, Sweden and the United Kingdom, all held by EVOLAN PHARMA AB [1].
- The largest independent trial found nothing. Among 461 analysed patients with COVID-19 respiratory failure, the odds of a better outcome were 1.11 (p = 0.54) and deaths by day 90 were 38 against 36 per cent. Its monitoring board closed the aviptadil arm for futility on 25 May 2022 [2].
- The American regulator refused emergency use twice, in November 2021 — citing insufficient data and safety reviewed in only 131 randomised patients — and again on 1 July 2022 [3], [4].
- The manufacturer's own trial missed its primary endpoint. In 196 patients, being alive and free of respiratory failure at day 60 gave an odds ratio of 1.6, and the paper says plainly that there was no difference from placebo [5].
- Pooled across all the ARDS evidence, the effect is zero. Nine studies with 665 patients gave a pooled odds ratio for survival of 1.01 (p = 0.93). Uncontrolled case series had suggested far more: 48 survivors out of 54 (88.9 per cent) [6].
- It is not banned in sport, and nobody has published its pharmacokinetics. The 2026 prohibited list does not name it [7], and a PubMed search for aviptadil with pharmacokinetics returned no results at all [8].
What it is
VIP stands for vasoactive intestinal peptide, a chain of 28 amino acids that the human body produces itself. It is cut out of a larger precursor protein of 170 amino acids, made by the gene VIP. Its last building block carries a chemical cap called an amide [9].
The same peptide, made synthetically, is a drug substance with its own international name: aviptadil. That is the whole difference between the two words — two PubChem entries, one titled after each name, share a single formula and structural key [10].
It was first isolated from pig gut in 1970, and the pig and human sequences are identical. The route to a medicine ran through a small American company, then a London firm, and today sits with the Swedish company EVOLAN PHARMA AB [11], [12].
Quick facts
| Field | Value | Ref |
|---|---|---|
| Names | VIP (the body's own peptide); aviptadil (international non-proprietary name of the drug substance) | [9], [10] |
| Other names | RLF-100 and ZYESAMI (the COVID-19 development programme); Invicorp, Corpin, Procivni, Procorp (brands of the combination in Denmark, Germany, France, the Nordics and the United Kingdom) | [1], [10] |
| Class | Neuropeptide of the secretin and glucagon superfamily; as a drug, a relaxant of smooth muscle and a widener of blood vessels | [9], [11] |
| Structure | Linear 28-amino-acid peptide, HSDAVFTDNYTRLRKQMAVKKYLNSILN, no disulfide bridge, amide cap at the end | [9] |
| Formula and mass | C147H237N43O43S, 3326.8 g/mol | [10], [13] |
| Half-life | Never published in humans | [8] |
| Routes | Injection in the approved medicine; intravenous infusion and inhalation in research only | [11] |
| Status | Approved and prescription-only in seven European markets, always in combination, never alone | [1], [11] |
| ATC code | G04BE70, assigned to the combination | [14] |
| Marketing authorisation holder | EVOLAN PHARMA AB | [1] |
| CAS registry number | 40077-57-4 | [10] |
| PubChem CID | 16132300 and 53314964, the same substance twice | [10] |
| UNII, InChIKey | A67JUW790C, VBUWHHLIZKOSMS-RIWXPGAOSA-N | [10] |
| UniProt, ChEMBL | P01282, CHEMBL1981592 | [9], [13] |
How it works
VIP works through two docking points on the cell surface, and everything else follows from what those two receptors do.
- It activates the receptors VPAC1 and VPAC2. Both signal through a rise in the internal messenger cAMP, which relaxes smooth muscle and widens blood vessels [9].
- A third receptor, PAC1, is the dividing line. VIP binds it only weakly; it is the preferred receptor of the related peptide PACAP, and that single difference is why the two are not interchangeable [9].
- In the approved medicine the two ingredients pull in opposite directions. Aviptadil relaxes smooth muscle and acts mainly on the mechanism that traps blood in the tissue, while its partner phentolamine increases arterial inflow instead. The combination exists for that complementarity [11], [15].
- Neuroprotective and immune-damping effects have been described, but they rest on laboratory work, not on controlled human results [9].
- The lung rationale was a hypothesis, not a finding. Preclinical work suggested that VIP raises production of the lung's surface film, damps inflammatory signals and blocks viral replication in lung cells. That was the stated reason for the COVID-19 trials, and those trials did not confirm it [5].
One piece of physiology belongs here. When the body itself produces too much VIP, the leading symptom is a watery diarrhoeal illness — an effect of excess, not evidence of any benefit [9].
What the trials found
Around 13 genuine trials of the substance exist, going back to a phase 1 study in 1998. They split cleanly: the respiratory programme failed, and the urological one supports an approved product [16].
The largest independent COVID-19 trial
Phase 3 RCT The ACTIV-3b/TESICO trial enrolled 473 adults in hospital with COVID-19 respiratory failure across 28 American centres; 94 per cent were in intensive care. Of 471 randomised patients, 461 entered the main analysis: 231 on aviptadil, 230 on placebo [2].
Phase 3 RCT The primary endpoint was a six-step outcome scale at day 90. The odds of landing in a better category were 1.11 (95 per cent confidence interval 0.80 to 1.55; p = 0.54) — no difference at all. On 25 May 2022 the independent monitoring board advised stopping the arm for futility [2].
Phase 3 RCT Deaths told the same story. By day 90, 86 people had died on aviptadil and 83 on placebo, a cumulative 38 against 36 per cent (hazard ratio 1.04; 95 per cent confidence interval 0.77 to 1.41; p = 0.78). The programme's central claim, a halving of deaths, did not survive this trial [2].
ACTIV-3b/TESICO, 461 analysed patients (231 aviptadil, 230 placebo) with COVID-19 respiratory failure, 28 American centres, enrolment April 2021 to May 2022. Hazard ratio 1.04 (95 per cent confidence interval 0.77 to 1.41; p = 0.78); the arm was stopped for futility. Source [2].
The manufacturer's trial, and what it did not show
Phase 2b/3 RCT This is the trial that both emergency applications rested on: 196 patients with COVID-19 respiratory failure at ten American hospitals, randomised two to one. The primary endpoint was being alive and free of respiratory failure at day 60. It was missed: odds ratio 1.6 (95 per cent confidence interval 0.86 to 3.11) [5].
Phase 2b/3 RCT The authors also report an odds ratio of 2.0 for survival at day 60 (1.1 to 3.9; p = 0.035), better oxygenation and a smaller rise in interleukin 6 at day 3 (p = 0.02). Their own conclusion is plain: the primary endpoint missed significance, so there was no difference from placebo [5].
Once a primary endpoint is missed, the analyses behind it lose their footing, and the subgroup results were not corrected for repeated testing. The company's 2021 annual report gives the missed endpoint as p = 0.085 across all patients and all sites [3], [5].
Everything pooled
Meta-analysis A 2025 systematic review searched six databases to October 2025 and pooled nine studies with 665 patients, 361 of them treated. The pooled odds ratio for survival was 1.01 (95 per cent confidence interval 0.72 to 1.42; p = 0.93) [6].
Meta-analysis The instructive part is the gap inside that paper. In the uncontrolled case series 48 of 54 patients survived (88.9 per cent), with better oxygenation and inflammatory markers. Once controls were present, the effect disappeared [6].
Inhaled use, a smaller and disputed result
Phase 2 RCT A Turkish trial randomised 80 hospital patients at nine centres, double-blind and placebo-controlled. Mean time to discharge was 7.8 ± 4.0 days against 10 ± 5.0 days (p = 0.049) [17].
Phase 2 RCT The breathlessness score differed at day 7 (p = 0.033) but not at day 3 (p = 0.090), and lung imaging improved more by day 28 (p = 0.028). Deaths were 5.1 against 12.2 per cent, with no significance test reported [17].
That is a small trial right on the significance threshold. Two methodological letters have appeared against it, with replies from the authors, and it contradicts the two large intravenous trials, though the route differs [18], [19].
Erectile dysfunction, where the approval comes from
Open-label cross-over The licensing trial compared the combination with alprostadil in 187 men in its first phase. Fewer men reached a grade 3 erection with the combination: 73 per cent (137 of 187) against 83 per cent (155 of 187), p = 0.002. In the second phase, response rates by injection were near-identical, 84 per cent of 395 against 83 per cent of 380 [11].
Open-label cross-over Tolerability ran the other way, and that is the product's place. Adverse events affected 30 per cent of men on the combination against 46 per cent on alprostadil. Injection pain occurred with 3 per cent of combination injections against 28 per cent, and facial flushing the other way round, 16 against 3 per cent (both p < 0.001) [11].
Licensing trial VP007, open-label cross-over, 187 men in phase 1 and 107 in phase 2, as assessed by the Scottish Medicines Consortium in 2017. Both differences p < 0.001. The trade-off — less pain, more flushing — is the reason the product exists alongside alprostadil. Source [11].
Observational A British centre reviewed 308 men referred after alprostadil failed or hurt too much, with a mean follow-up of 13.3 months. In all, 182 of 308 (59 per cent) resumed penetrative sexual activity at three months. The split was wide: 76 per cent of those referred for pain against 36 per cent of those referred for failure (p < 0.0001) [20].
Migraine, an unintended human signal
Randomised cross-over In 21 migraine patients, a two-hour infusion triggered an attack in 15 of them (71 per cent; 95 per cent confidence interval 48 to 89 per cent), against 1 of 21 after placebo (5 per cent; 0 to 24 per cent), p < 0.001. A shorter infusion did not do this; duration was decisive [21].
Randomised cross-over A head-to-head comparison with PACAP38 covered 22 evaluable patients: migraine-like attacks followed in 16 of them (73 per cent) after PACAP38, but in only 4 (18 per cent) after VIP, p = 0.002. Three of the four VIP responders also responded to PACAP38 [22].
What is still unknown
- What the approved strength does, and what the VIP component contributes. The licensing assessment records that response and safety were not reported separately for the licensed strength, and no trial has ever tested VIP against placebo without its combination partner [11].
- Anything about women or young people, or beyond about a year of use. The approval covers adult men only, and the largest published series has a mean follow-up of 13.3 months [11], [20].
- Whether subcutaneous use is safe. There is no approval and no published safety study for that route anywhere [8].
Side effects and safety
The safety record splits by route, and mixing the two gives a false picture: for the approved injectable medicine the profile is well described and mostly local, while for intravenous research use the dominant effects are circulatory and neurological.
- Facial flushing is the most common effect, at 16 per cent of injections in the licensing trial against 3 per cent for alprostadil. The British series recorded it in 69 of 308 men (22.5 per cent) [11], [20].
- Bruising and bleeding at the injection site each occurred with about 1 per cent of injections, and the assessment notes bruising becomes less frequent as patients gain practice [11], [23].
- Roughly 10 per cent of patients experience adverse reactions overall, according to the summary of product characteristics as quoted in the British assessment [23].
- Prolonged painful erection is rare but real. The licensing trial recorded no case; the 308-man series recorded one (0.3 per cent) [11], [20].
- Blood pressure can fall, because the peptide is a strong widener of blood vessels; given intravenously, that is what limits it [9].
- Migraine attacks follow prolonged intravenous infusion in people prone to migraine, in 71 per cent against 5 per cent on placebo [21].
- In the large COVID-19 trial the safety composite was numerically worse on the drug: 146 of 231 (63 per cent) against 129 of 230 (56 per cent). The odds ratio was 1.40 (95 per cent confidence interval 0.94 to 2.08; p = 0.10), not significant, but it rules out calling the substance harmless [2].
Two label facts carry weight. The product is contraindicated in patients taking heparin or oral anticoagulants, unlike alprostadil. The first injections must be given by medically trained staff, with regular medical review afterwards [11], [23].
The published picture also has holes: no pharmacokinetics, no long-term data, none in women or young people, and nothing at all on the subcutaneous route [8], [11].
Why this page lists no doses
Aviptadil is the active substance of a prescription-only medicine approved in Germany and six other European countries. Public-facing dosing information for prescription medicines is not permitted under German advertising law, and this page therefore carries none [1].
That applies to every unit and every context: nothing from the product information, nothing from the trials, nothing for the intravenous or inhaled research routes. Dosing for an approved injectable belongs with the prescribing doctor, not on a reference page.
Development and approval status
The status is split in two, and that split explains the whole substance: in erectile dysfunction it is an approved medicine in continuing clinical use, in respiratory medicine a failed candidate [1], [2].
From pig gut to a stopped trial
- 1970The peptide is isolatedFound in pig gut; the pig and human sequences turn out to be identical, ref [11]
- 1998First registered trialA phase 1 study in ARDS and sepsis opens in the United States — the lung hypothesis is not new, ref [16]
- 2015The combination reaches the British marketProduct availability is dated to November 2015 in the Scottish assessment, ref [11]
- 2020COVID-19 programme startsAn investigational application is filed in March and cleared within days, ref [24]
- 2021First refusalThe manufacturer trial misses its primary endpoint; in November the American regulator declines emergency use, refs [3], [5]
- 2022Futility and a second refusalThe independent trial arm is stopped on 25 May; the second emergency application is refused on 1 July, refs [2], [4]
- 2023The independent results appearLancet Respiratory Medicine publishes no difference from placebo, ref [2]
- 2025Still in clinical useA British centre publishes a series of 308 men treated with the approved combination, ref [20]
- 1970 the peptide is isolated from pig gut [11].
- 1998 the first registered trial, a phase 1 study in ARDS and sepsis, opens [16].
- November 2015 the combination is available on the British market [11].
- March 2020 the COVID-19 investigational application is filed and cleared [24].
- February 2021 the manufacturer trial finishes follow-up with its primary endpoint missed [3].
- November 2021 the American regulator declines emergency use and also refuses an accelerated-review status [3].
- January 2022 a private investor class action is filed; the plaintiffs withdraw it voluntarily in June, and no court ever rules on it [3].
- May and July 2022 the independent trial arm is stopped for futility, and the second emergency application is refused [2], [4].
- June 2023 the independent results are published: no difference from placebo [2].
| Market | Status | Since or note |
|---|---|---|
| Germany | Approved | Prescription-only, number 91159.00.00 |
| United Kingdom | Approved | Prescription-only, specialist initiation |
| European Union | National | No central approval; seven national ones |
| United States | Unapproved | Emergency use refused twice |
| Canada | Unapproved | No product record |
| Switzerland | Unapproved | Not listed |
| Australia | Unverified | Register unreachable |
The European entries come from the European register of nationally approved products, dated 27 October 2022; the national registers themselves could not be read [1].
The American, Canadian and Swiss entries are database queries run with working control substances on 17 September 2026, so a blank means absence [25], [26], [27]. The Australian register could not be reached at all, and stays unverified [28].
There has never been a central European approval, and none was ever withdrawn [29].
Two things that are often asserted are not on the record. No securities regulator proceeding is traceable, either in the company's own filings or in a full-text search of American securities filings [3], [24], [30]. No warning letter exists for the substance or its development name either, against control queries that returned dozens of hits [31].
What did happen was regulatory refusal on the merits, three times: emergency use in November 2021 and on 1 July 2022, and the accelerated-review status in November 2021 [3], [4].
The grey-market position is documented too. Three bulk-ingredient registrations sit in the American drug code directory, two of them from the past fifteen months [32]. The substance also stands in category 1 of the list of substances nominated for pharmacy compounding — under evaluation, not on the final cleared list [33]. Neither is an approval.
The broader legal picture is under are peptides legal and FDA-approved peptides.
Anti-doping
VIP is not prohibited in sport. A full-text search of the 2026 prohibited list found no match for the substance, its development name or PACAP. Control terms in the same document returned hits [7]. It is likewise absent from the annex to the German anti-doping statute [34].
The catch-all class S0 is the clause that would normally capture a peptide like this, and it is worth saying why it does not. S0 reaches "any pharmacological substance … with no current approval by any governmental regulatory health authority for human therapeutic use", and aviptadil has such approvals, in seven European countries [1], [7].
That makes the doping question and the approval question the same one: were this merely an investigational substance, S0 would prohibit it at all times. One separate rule applies, since large-volume intravenous infusions are prohibited as a method outside hospital treatment [7]. The wider picture is at peptides banned in sport.
Compared with related peptides
| Substance | Receptors | Status | Strongest human result | Ref |
|---|---|---|---|---|
| VIP (aviptadil) | VPAC1, VPAC2 | Approved in seven European markets, in combination | 59 per cent of 308 men resumed sexual activity; no effect in COVID-19 | [2], [20] |
| PACAP | VPAC1, VPAC2 and PAC1 | Not approved | Triggered migraine in 73 per cent against 18 per cent for VIP | [22] |
| Pemziviptadil | VIP receptors, long-acting analogue | Not approved; all trials terminated | None; programmes stopped before results | [16] |
| Sermorelin | GHRH receptor, same superfamily | See its own page | See its own page | — |
| PT-141 | Melanocortin receptors | See its own page | See its own page | — |
The first two rows carry the useful contrast. PACAP shares two of VIP's receptors and adds a third, and that extra receptor changes the human response by a factor of four in the only head-to-head test [22].
Pemziviptadil matters for the opposite reason. Routinely mistaken for a long-acting form of aviptadil, it is a different molecule from a different company, and all three of its registered trials were terminated. Its results belong to it, not to VIP [16].
Common misconceptions
- "VIP and aviptadil are two different substances." One peptide, two names: VIP for the body's own messenger, aviptadil for the synthetic drug substance, sharing one formula and one structural key [10].
- "Aviptadil is approved as a medicine in its own right." No single-substance product exists anywhere. What is approved is the fixed combination with phentolamine, which does not make the active substance any less prescription-only [1], [11].
- "VIP and PACAP are interchangeable." They share two receptors, but PACAP also binds a third with high affinity and VIP does not — head to head, 73 per cent against 18 per cent [22].
- "Pemziviptadil is just long-acting aviptadil." PB1046, as it is also called, is a different molecule from another company, tested in three trials that were all terminated; its data cannot be credited to aviptadil [16].
- "The company was sanctioned by the authorities for overstating the results." It was not. There was a private class action, withdrawn voluntarily by the plaintiffs, and no court ruling; no warning letter and no securities regulator proceeding is on record [3], [30], [31].
- "Inhaled and intravenous use amount to the same thing." Intravenously the substance failed in the largest trial; inhaled, one small trial was positive and two programmes were abandoned. Neither route is approved anywhere [2], [17].
Frequently asked questions
Is VIP approved as a medicine anywhere?
Yes, but never on its own. As part of a fixed injectable combination with phentolamine it holds national approvals in seven countries: Germany, Denmark, Finland, France, Norway, Sweden and the United Kingdom. The German approval number is 91159.00.00. No country has approved a single-substance product, and it is prescription-only everywhere it is approved.
Did VIP work against COVID-19?
No. The manufacturer's trial in 196 patients missed its primary endpoint. The large independent trial randomised 471 patients and was stopped early for futility. It found an odds ratio of 1.11 for a better outcome (0.80 to 1.55; p = 0.54), and deaths by day 90 of 38 against 36 per cent.
Why did the American regulator refuse aviptadil?
Twice, and for stated reasons. In November 2021 the agency wrote that insufficient data on the known and potential benefits and risks prevented an emergency authorisation. It noted that safety had been reviewed in only 131 randomised patients. A second application in February 2022, built on an after-the-fact subgroup analysis, was refused on 1 July 2022.
Was there a regulatory sanction against the company behind aviptadil?
No. A full-text search of the American warning letter database in September 2026 returned nothing for aviptadil, with working control queries. No securities regulator proceeding is on record either. What existed was a private investor class action filed in January 2022, which the plaintiffs voluntarily withdrew in June 2022, so no court ever ruled on the allegations.
Is VIP banned in sport?
No. It appears nowhere on the 2026 prohibited list, and nowhere in the annex to the German anti-doping statute. The catch-all class for non-approved substances does not reach it either. That class covers only substances with no current approval by a government health authority, and aviptadil has European approvals.
What are the known side effects of VIP?
For the approved injectable use, facial flushing is the most common problem. It was seen in 16 per cent of injections in the licensing trial, and in 69 of 308 men (22.5 per cent) in a British series. Bruising and bleeding at the injection site occur in about 1 per cent, and prolonged painful erection in one man of 308.
How long does VIP stay in the body?
Nobody has published the answer. A PubMed search for aviptadil together with pharmacokinetics returned no results at all in September 2026. Half-life, distribution and route of elimination in humans cannot be stated from the accessible literature, which is an unusual gap for a substance approved for more than a decade.
Can VIP be bought as a research peptide?
Raw material for it is registered in the United States as a bulk ingredient. The substance also sits in category 1 of the American compounding list, meaning under evaluation rather than cleared. None of that is an approval. Subcutaneous use, which is how the grey market offers it, has no approval and no published safety study anywhere.
Sources
- European Medicines Agency (2022). List of nationally authorised medicinal products — active substance: aviptadil / phentolamine mesilate. Procedure PSUSA/00010814/202202, EMA/855871/2022, 27 October 2022. Full table of national approvals: Germany 91159.00.00, Denmark 53257, 58026, 19049, 19050 and 58029, Finland 31902, France six pack presentations, Norway 13-9854, Sweden 50365, United Kingdom and Northern Ireland PL 44616/0001; marketing authorisation holder EVOLAN PHARMA AB throughout.
- Brown SM, Barkauskas CE, Grund B, Sharma S, Phillips AN, … Lane HC; ACTIV-3b/TESICO Study Group (2023). Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. The Lancet Respiratory Medicine 11(9):791–803. PMID 37348524. DOI 10.1016/S2213-2600(23)00147-9.
- NRx Pharmaceuticals, Inc. (2022). Annual report on Form 10-K for the year ended 31 December 2021, filed 31 March 2022, CIK 0001719406. Contains the wording of the November 2021 refusal, the refused accelerated-review status, the missed primary endpoint at p = 0.085, the second application of 10 February 2022, and the class action of 18 January 2022 in Item 3.
- NRx Pharmaceuticals, Inc. Press release of 1 July 2022 on the refusal of the second emergency use application.
- Youssef JG, Lavin P, Schoenfeld DA, Lee RA, Lenhardt R, … Jayaweera D (2022). The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial. Critical Care Medicine 50(11):1545–1554. PMID 36044317. DOI 10.1097/CCM.0000000000005660.
- Udupa AA, Todur P, Chaudhuri S, Gupta N, Bhat VR, … Hanumaiah G (2025). Aviptadil therapy in acute respiratory distress syndrome patients: a systematic review and meta-analysis. Indian Journal of Critical Care Medicine 29(11):942–953. PMID 41368449. DOI 10.5005/jp-journals-10071-25084.
- World Anti-Doping Agency (2026). Prohibited list 2026, full text checked on 17 September 2026: no match for "aviptadil", "vasoactive", "intestinal", "VIP" or "PACAP", including the alphabetical index, against working control terms in the same file. Wording of class S0 and of method M2.2 read in the original.
- PubMed, queried on 17 September 2026 for "aviptadil AND pharmacokinetics": no records. Half-life, volume of distribution and elimination route in humans are therefore not stated on this page.
- UniProt Consortium. Entry P01282 (VIP peptides, Homo sapiens), retrieved 17 September 2026. Mature peptide at positions 125–152 of a 170-amino-acid precursor, sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN, amide cap at position 152, family assignment "glucagon family", receptor function for VPAC1 and VPAC2.
- PubChem (NCBI). CID 16132300 ("Aviptadil") and CID 53314964 ("Vasoactive intestinal peptide"), retrieved 17 September 2026. Both carry C147H237N43O43S, 3326.8 g/mol and InChIKey VBUWHHLIZKOSMS-RIWXPGAOSA-N, together with CAS 40077-57-4 and UNII A67JUW790C, and a synonym list holding Invicorp, Zyesami and RLF-100.
- Scottish Medicines Consortium (2017). Aviptadil / phentolamine solution for injection (Invicorp). SMC No 1284/17, advice of 10 November 2017, published 11 December 2017. Licensed indication, product availability from November 2015, full assessment of licensing trial VP007 including its methodological weaknesses, and the note that outcomes for the licensed strength were not reported separately.
- Keijzers GB (2001). Aviptadil (Senatek). Current Opinion in Investigational Drugs 2(4):545–549. PMID 11566015. Earliest development overview of the substance.
- ChEMBL (EMBL-EBI). Entry CHEMBL1981592 (aviptadil), retrieved 17 September 2026: formula C147H237N43O43S, full molecular weight 3326.84, synonyms flagged as INN, USAN and BAN.
- Gelbe Liste Pharmindex. Active substance profile: aviptadil, retrieved 17 September 2026. Only source found for ATC code G04BE70, which is assigned to the combination. Secondary source; a cross-check in the World Health Organization ATC index was not possible.
- Dinsmore WW, Wyllie MG (2008). Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction. BJU International 102(8):933–937. PMID 18485029. DOI 10.1111/j.1464-410X.2008.07764.x. Describes the opposing mechanisms of the two combination partners.
- ClinicalTrials.gov, application programming interface version 2, individual records retrieved 17 September 2026: NCT00004494 (phase 1 in ARDS and sepsis, from 1998), NCT04843761 (ACTIV-3b/TESICO), NCT04360096 and NCT05137795 (inhaled programmes, terminated and withdrawn), NCT04844580 (Turkish inhalation trial), and NCT04433546, NCT03556020 and NCT03315507, which concern the separate molecule pemziviptadil (PB1046) and were all terminated.
- Esendagli D, Sarı N, Akhan S, Arslan S, Doğan Öntaş İA, … Inkaya AC (2025). Inhaled aviptadil for recovery of lung damage due to COVID-19. Medical Principles and Practice 34(2):191–200. PMID 39870064. DOI 10.1159/000543773. Randomised, double-blind, placebo-controlled, 80 patients at nine centres.
- Gao C, Lu X (2026). Methodological considerations in a trial of inhaled aviptadil for COVID-19 pneumonia. Medical Principles and Practice 35(1):90–91. PMID 40928995. DOI 10.1159/000548272.
- Charles EJ, Shaikh FA, Nemeth ZH (2026). Inhaled aviptadil for post-COVID lung injury: early promise, future directions. Medical Principles and Practice 35(1):95–96. PMID 40675136. DOI 10.1159/000547366.
- Al-Mitwalli A, Holden F, Di Giovanni A, Gobbo A, Shah M, Chiriaco G, Sangster P, Ralph D, Lee WG (2025). Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction. The Journal of Sexual Medicine 22(5):726–730. PMID 40192471. DOI 10.1093/jsxmed/qdaf067. Largest published series: 308 men, mean follow-up 13.3 months.
- Pellesi L, Al-Karagholi MA, De Icco R, Coskun H, Elbahi FA, … Ashina M (2021). Effect of vasoactive intestinal polypeptide on development of migraine headaches: a randomized clinical trial. JAMA Network Open 4(8):e2118543. PMID 34357396. DOI 10.1001/jamanetworkopen.2021.18543.
- Amin FM, Hougaard A, Schytz HW, Asghar MS, Lundholm E, … Ashina M (2014). Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain 137(Pt 3):779–794. PMID 24501094. DOI 10.1093/brain/awt369. Head-to-head comparison of VIP and PACAP38 in 22 evaluable patients.
- Bedfordshire and Luton Joint Prescribing Committee (2019). Aviptadil / phentolamine injection for erectile dysfunction. JPC Bulletin 284, December 2019. Formulary status "specialist initiation, GP continuation"; presentation as a ready-to-use solution in a glass ampoule; adverse reaction rate of approximately 10 per cent per the summary of product characteristics; contraindication with heparin and oral anticoagulants.
- NRx Pharmaceuticals, Inc. (2023). Annual report on Form 10-K for the year ended 31 December 2022, filed 31 March 2023. Records the March 2020 investigational application and its clearance, the November 2022 settlement with the development partner, and the company's own description of the results alongside the regulator's classification of them as hypothesis generating. Item 3 names only an arbitration over a fee claim, no regulator proceeding.
- openFDA, dataset drugsfda, queries
openfda.generic_name:"aviptadil"andproducts.active_ingredients.name:"AVIPTADIL", 17 September 2026: no matches. No American application of any kind. - Health Canada, drug product database, active-ingredient endpoint, 17 September 2026: empty result, against 4 records for the control substance phentolamine and 51 for somatropin.
- Swissmedic, extended list of authorised human medicines (29,625 text cells), 17 September 2026: no match for aviptadil, Invicorp, phentolamine or "vasoaktiv", against 10 matches for alprostadil and 19 for tirzepatide.
- Therapeutic Goods Administration (Australia): the register search was unreachable on 17 September 2026, including for the control query, and the full text of the Poisons Standard instrument F2026L00633 could not be downloaded. Australia is therefore recorded as unverified rather than as absent.
- European Commission, Union register of medicinal products, lists of current and expired authorisations, 17 September 2026: no match for aviptadil, Invicorp or phentolamine in either list, against working controls. No central European approval was ever granted or withdrawn.
- U.S. Securities and Exchange Commission, EDGAR full-text search, 17 September 2026: 235 documents mention aviptadil; combined with "SEC investigation" the search returns none, and with "subpoena" only unrelated contract exhibits.
- U.S. Food and Drug Administration, warning letters, full-text search 17 September 2026: 0 hits for "aviptadil", "Zyesami" and "vasoactive intestinal", against 44 for "peptide", 146 for "semaglutide" and 112 for "tirzepatide" through the same interface.
- openFDA, NDC directory, query
generic_name:"aviptadil", database state 16 September 2026: three bulk-ingredient registrations, no finished medicine. Registrations dated 2 June 2021, 1 July 2025 and 4 July 2026. - U.S. Food and Drug Administration (2026). Bulk drug substances nominated for use in compounding under section 503A, document state 14 May 2026: "Vasoactive Intestinal Peptide" appears in category 1, substances under evaluation, and not on the final list under 21 CFR 216.23.
- Germany, annex to section 2(3) of the anti-doping act, official citation BGBl. 2023 I no. 67, checked 17 September 2026: no entry for aviptadil, "vasoaktiv", VIP or PACAP, against present control entries for somatropin, erythropoietin and growth hormone.
Cite this page
Every register behind the status table was queried on 17 September 2026, with two limits: the European approvals are documented as of 27 October 2022, and Australia could not be checked at all.
myPeptides Research & Editing. (2026). VIP (aviptadil): what the trials show, status and safety. Version 1.0, 17 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/vip
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Change |
|---|---|---|
| 1.0 | 2026-09-17 | Initial publication |
Last verified: 17 September 2026. Next review: on any confirmation of the European approvals after 2022, on any Australian register result, or on any publication of human pharmacokinetics.