Evidence memo / Neuro & mental health

VIP / aviptadil

Also: vasoactive intestinal peptide · aviptadil · RLF-100

Aviptadil is a synthetic form of vasoactive intestinal peptide (VIP), a natural signaling molecule with effects on blood vessels, the lungs, and other tissues. It is used in some countries in a combination injection for erectile dysfunction, and it was tested in COVID-19 respiratory failure, where large trials were largely negative. It is not approved in the US for respiratory use. The Watchlist boundary is separating its narrow approved context from the broader claims and the disappointing COVID results.

Claim-specific / contestedContext-dependentInvestigationalSafety / regulatory watch

The verdict

Our read at a glance.

Whether aviptadil's VIP biology and its narrow approved use support the broader respiratory and other claims made for it, given largely negative COVID-19 trial results.

The signal
Aviptadil is used in a combination injection for erectile dysfunction in some countries. For COVID-19 respiratory failure it was tested in trials, including a large independent trial, that did not show clear benefit. Evidence for broader uses is limited.
The unknown
Whether VIP-based therapy has a meaningful role in any lung or vascular condition, given the negative COVID-19 results, and how its narrow approved use applies elsewhere.
Our read
A real signaling peptide with a narrow approved use and a disappointing COVID-19 record, not a proven lung therapy. Aviptadil's VIP biology is genuine, but its large respiratory trials were largely negative, so the broader claims should be read with that in mind.

The mechanism

How it works.

Aviptadil is a synthetic copy of vasoactive intestinal peptide (VIP), a 28-amino-acid signaling molecule the body uses to relax smooth muscle. It binds VIP receptors on blood vessels and airways, relaxing them so vessels widen and airways open, and it also acts on type II cells in the lung, which produce the surfactant that keeps air sacs from collapsing. These actions explain its use in an injected combination for erectile dysfunction and were the rationale for testing it in severe COVID-19 lung failure, where large trials did not show clear benefit.

Safety & regulatory boundary

The consequential part.

Aviptadil is not approved in the US for respiratory or general use, and large COVID-19 trials did not show clear benefit. A jurisdiction-specific combination product for erectile dysfunction does not validate respiratory or other claims. It can lower blood pressure and cause other effects, and research-labeled or compounded aviptadil is not the same as any approved product.

What's next

What we're watching.

Any further controlled trials in lung or vascular conditions, and regulatory status across regions.

Context

Why this is discussed.

Aviptadil drew wide attention during the pandemic as a proposed treatment for severe COVID-19 lung failure, and VIP biology keeps interest in it for lung and vascular conditions.

The evidence base

20 cited references.

Registered trials8

Inhaled ZYESAMI (Aviptadil Acetate) for Treatment of Severe COVID-19

ClinicalTrials.gov · PHASE3 · WITHDRAWN · 2021-12-15

I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients

ClinicalTrials.gov · PHASE2 · ACTIVE_NOT_RECRUITING · 2020-07-31

ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19

ClinicalTrials.gov · PHASE3 · COMPLETED · 2021-04-20

Inhaled Aviptadil for the Treatment of COVID-19 in Patients at High Risk for ARDS

ClinicalTrials.gov · PHASE2 · TERMINATED · 2021-05-18

Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure

ClinicalTrials.gov · PHASE2/PHASE3 · COMPLETED · 2020-05-15

A Clinical Study Evaluating Inhaled Aviptadil on COVID-19

ClinicalTrials.gov · PHASE2 · COMPLETED · 2021-03-10

ZYESAMI (Aviptadil) Intermediate Population Expanded Access Protocol (SAMICARE)

ClinicalTrials.gov · NO_LONGER_AVAILABLE · registry record

Indexed literature (PubMed)12

Liposomal vasoactive intestinal peptide

Sethi V et al. · Methods Enzymol · 2005

Anticipated pharmacological role of Aviptadil on COVID-19

Mukherjee T et al. · Environ Sci Pollut Res Int · 2022

Keep reading

Related published memos.