Aviptadil

VIP was first isolated from hog intestine in 1970 and found to widen blood vessels, lower blood pressure, raise cardiac output and stimulate breathing¹. It acts through two G-protein-coupled receptors, VPAC1 and VPAC2, which signal largely through the enzyme adenylyl cyclase, and it helps regulate secretions, hormone release and immune responses². Injected into the erectile tissue of the penis, its blood-vessel-widening action supports erection; in Invicorp it is paired with phentolamine, an alpha-adrenergic blocker that also relaxes vascular smooth muscle. Interest in lung injury stems from VIP's roles in immune regulation and reports that it may help in inflammatory disease², which is why it was trialed in critically ill COVID-19 patients⁵.

Most human evidence comes from erectile dysfunction studies of the VIP-phentolamine combination. In a multicentre, placebo-controlled study of men with mainly non-psychogenic erectile dysfunction, 75% responded to the combination versus 12% to placebo in the controlled phase³. In a randomized crossover comparison with alprostadil in 187 men, alprostadil worked in more men in the first phase (83% versus 73%); among men who responded to both, rates of erections suitable for intercourse were then similar, and more men preferred VIP-phentolamine, which the authors linked to its much lower rate of injection pain⁴. For lung disease the results so far are negative: in the NIH-funded TESICO trial of 461 critically ill COVID-19 patients with respiratory failure, intravenous aviptadil did not improve 90-day recovery or survival compared with placebo, and the aviptadil comparison was stopped for futility⁵.

Aviptadil is not FDA-approved. Combined with phentolamine it has held a UK marketing authorisation as Invicorp for erectile dysfunction, and NHS Wales recommended it in 2017 for men whose erectile dysfunction has not responded to oral PDE5 inhibitors⁶.

In the erectile dysfunction trials, the main side effect was temporary facial flushing (with about 40% of injections in one study and 16-17% in another), with little injection pain and rare prolonged erection (priapism)^3,4. In the COVID-19 trial, a combined measure of death, serious adverse events, organ failure, serious infection or severe adverse events by day 5 occurred in 63% on aviptadil versus 56% on placebo, a difference that was not statistically significant⁵.

1. Said & Mutt, Science 1970PubMed
2. Couvineau et al., Br J Pharmacol 2012PubMed
3. Dinsmore et al., BJU Int 1999PubMed
4. Shah et al., Curr Med Res Opin 2007PubMed
5. Brown et al., Lancet Respir Med 2023PubMed
6. AWMSG (NHS Wales) appraisal 1117: Invicorp, 2017awttc.nhs.wales