VIP / aviptadil

What it is

Vasoactive intestinal peptide, or VIP, is a 28-amino-acid peptide the body makes. Aviptadil is the synthetic human sequence used in investigational products and listed by FDA under UNII A67JUW790C. RLF-100 and ZYESAMI are development names, not proof that another product is the same thing.

Endogenous VIP, synthetic aviptadil, aviptadil acetate, and route-specific intravenous or inhaled formulations are not automatically interchangeable. Evidence must retain exact substance, formulation, route, indication, and clinical material; a shared name does not establish trial equivalence.

Why people care

Aviptadil attracted attention through emergency respiratory-development programs, orphan designations, and claims based on VIP's vasodilatory and immunologic physiology. The record includes randomized human trials, but trial phase, orphan status, secondary analyses, and endogenous peptide biology are often overstated as approval or proven clinical benefit.

What humans actually show

Aviptadil is a synthetic form of the endogenous 28-amino-acid vasoactive intestinal peptide. FDA orphan records say it is not approved for the designated indications, and the larger TESICO randomized trial did not improve its primary 90-day outcome in COVID-19 hypoxemic respiratory failure. Smaller studies do not establish approval, broad effectiveness, or interchangeability across routes and products.

• randomized human — Four hundred seventy-one adults hospitalized with COVID-19 hypoxemic respiratory failure in the TESICO platform trial; 461 received study treatment; Route: Intravenous aviptadil or placebo; Outcome: Primary 90-day six-category ordinal outcome and mortality: Aviptadil did not improve the primary outcome: odds ratio 1.11, 95% confidence interval 0.80 to 1.55. Mortality was 38% with aviptadil and 36% with placebo, and the trial stopped for futility. The seam: The result applies to the studied hospitalized COVID-19 population and intravenous product; A negative primary result cannot be converted into benefit from subgroup or mechanistic reasoning; The trial does not establish another route or indication; Trial material does not authenticate a nontrial product.
• randomized human — One hundred ninety-six critically ill adults with COVID-19 respiratory failure; Route: Intravenous aviptadil or placebo; Outcome: Alive and free of respiratory failure at day 60, with secondary survival analyses: The trial did not meet its primary endpoint. A secondary survival analysis favored aviptadil, but the later larger TESICO trial did not improve its primary outcome. The seam: The failed primary endpoint must remain visible beside secondary analyses; Smaller sample than TESICO; Secondary findings require cautious interpretation and replication; The result does not establish FDA approval.
• other human — Twenty people with sarcoidosis in an open-label four-week phase 2 study; Route: Inhaled aviptadil; Outcome: Bronchoalveolar-lavage inflammatory and regulatory-cell measures: The paper reported changes in tumor-necrosis-factor activity and regulatory T-cell measures. The seam: Small uncontrolled study; Laboratory and cellular outcomes rather than established clinical benefit; Inhaled route does not inherit intravenous evidence; The study does not establish approval or long-term safety.
• randomized human — Eighty adults hospitalized with COVID-19 in a randomized, double-blind, placebo-controlled inhaled aviptadil study; Route: Inhaled aviptadil or placebo, each added to standard care; Outcome: Time to discharge and secondary radiographic or symptom measures: The paper reported a shorter mean time to discharge and some favorable secondary outcomes. The seam: Modest single-study sample; Route and setting differ from TESICO; The finding does not override the larger negative primary trial; The study does not establish approval or product interchangeability.

Mechanistic and nonhuman evidence

• mechanistic — Human VIP peptide and its cognate receptor system; Route: Endogenous signaling and experimental aviptadil exposure; Outcome: Vasodilatory, secretory, and immunomodulatory signaling relevant to investigational respiratory uses: VIP biology supplies a mechanistic rationale for studying synthetic aviptadil, including hemodynamic and immune effects. The seam: Mechanism does not establish a clinical outcome; Endogenous physiology does not authenticate a formulation; Receptor activity does not establish approval; Hemodynamic activity may also be relevant to adverse effects.

FDA and U.S. status

FDA orphan-drug records for acute respiratory distress syndrome, sarcoidosis, and pulmonary arterial hypertension explicitly state that aviptadil or vasoactive intestinal peptide is not FDA approved for the orphan indication. An exact openFDA active-ingredient query returned no match, and the ClinicalTrials.gov intervention search returned nine investigational or expanded-access records. No FDA-approved aviptadil prescribing information was identified; the exact database no-match is preserved as a dated search result and is not used alone.

Risks and warning limits

• human trial: TESICO reported flushing, hypotension, diarrhea, and tachycardia more often with intravenous aviptadil than placebo.
• human trial: TESICO's composite safety outcome did not establish absence of uncommon, chronic, reproductive, route-specific, or population-specific risk.
• not characterized: No FDA-approved aviptadil prescribing information was identified, so this draft assigns no FDA-labeled contraindications, warnings, or adverse-reaction frequencies.

What remains unknown

• Whether aviptadil benefits a clearly defined population or indication in a reproducible adequately controlled program remains unresolved by the mixed trial record.
• Product- and route-specific long-term safety, uncommon risks, immunogenicity, pregnancy effects, contraindications, and interactions remain inadequately characterized.
• Whether intravenous findings transfer to inhaled aviptadil, sarcoidosis, pulmonary hypertension, or another indication is not established.
• The identity and quality of any material outside the cited clinical programs cannot be inferred from VIP, RLF-100, or ZYESAMI naming.

Product identity and quality limits

• Endogenous VIP and synthetic aviptadil are related identities but an endogenous measurement or mechanism is not evidence about a specific administered formulation.
• Aviptadil, aviptadil acetate, RLF-100, ZYESAMI, and route-specific formulations must retain their exact substance and product context.
• A shared name does not establish sequence, salt form, excipients, concentration, purity, sterility, aggregation state, stability, storage history, or trial equivalence.
• FDA orphan designation is neither marketing approval nor product authentication.

What has been studied together

• Aviptadil with remdesivir — coadministration studied: TESICO used a factorial platform design in which a subset entered both comparisons. The aviptadil comparison did not improve its primary outcome, and the subset does not establish a beneficial interaction or general combination safety.
• Aviptadil with vasodilatory or blood-pressure-lowering medicines — theoretical mechanism overlap: TESICO observed more hypotension with intravenous aviptadil. The source set does not provide an approved interaction section or adequate direct evidence establishing compatibility with another vasodilatory drug.
• Aviptadil with other peptides or respiratory products — no direct evidence: No adequate general coadministration program was identified in the dated search. Missing evidence does not establish compatibility or safety.

What people are hearing

These are claims this profile checks, not established conclusions.

• Claim under review: “Orphan-drug designation or a completed phase 3 trial means aviptadil is FDA approved.”
• Claim under review: “Randomized COVID-19 trials proved that aviptadil improves survival or recovery.”
• Claim under review: “Endogenous VIP, aviptadil, aviptadil acetate, RLF-100, and ZYESAMI establish one interchangeable product.”

Questions readers raise

• No reproducible community sample was collected for this profile.

The community-signal layer is not efficacy or safety evidence. Its current limits are:

• No reproducible community sample has been collected for this profile.
• Self-reports would be subject to selection and reporting bias.
• The identity and route of a product described in a self-report could not be verified.
• Concurrent medicines, health conditions, and supportive care could confound an anecdote.
• Reported outcomes could not be independently verified.
• Anecdotes cannot establish efficacy, safety, approval, product identity, or interaction compatibility.

What would change this answer

• A reproducible, adequately controlled trial with a prespecified patient-important primary outcome could change the current mixed and indication-specific efficacy boundary.
• An FDA approval action and final prescribing information would change the unapproved status and establish product-specific indication, identity, warnings, and interactions.
• Direct route-bridging and formulation-comparison evidence could change whether intravenous findings apply to an inhaled product; none was identified.

Sources and records

• WADA — 2026 Prohibited List

• Aviptadil substance record, UNII A67JUW790C — U.S. Food and Drug Administration Global Substance Registration System
• VIP vasoactive intestinal peptide gene record — National Center for Biotechnology Information
• Drugs@FDA API exact active-ingredient search for aviptadil — U.S. Food and Drug Administration
• Orphan Drug Designations and Approvals: vasoactive intestinal peptide for acute respiratory distress syndrome — U.S. Food and Drug Administration
• Orphan Drug Designations and Approvals: aviptadil for sarcoidosis — U.S. Food and Drug Administration
• Orphan Drug Designations and Approvals: vasoactive intestinal peptide for pulmonary arterial hypertension — U.S. Food and Drug Administration
• ClinicalTrials.gov intervention search for aviptadil — ClinicalTrials.gov
• PubMed aviptadil human-record search — National Library of Medicine
• Aviptadil and remdesivir for treatment of COVID-19 in the TESICO randomized trial — PubMed
• TESICO platform trial aviptadil comparison — ClinicalTrials.gov
• Intravenous aviptadil for critical COVID-19 respiratory failure — PubMed
• Intravenous aviptadil in critical COVID-19 — ClinicalTrials.gov
• Inhaled aviptadil in sarcoidosis — PubMed
• Inhaled aviptadil in hospitalized adults with COVID-19 — PubMed