Nereus Reduced Semaglutide-Induced Vomiting in Phase 3 Trial

Tradipitant (Nereus, Vanda Pharmaceuticals), an oral neurokinin-1 (NK-1) receptor antagonist, reduced the incidence of vomiting after a semaglutide dose in a phase 3 randomized, placebo-controlled trial, according to results announced by Vanda Pharmaceuticals.

Study 3601 (VP-VLY-686-3601) evaluated tradipitant for the prevention of vomiting associated with GLP-1 receptor agonist therapy. Tradipitant was approved in December 2025 for the prevention of motion-induced vomiting. Vanda said nausea and vomiting are leading reasons that patients stop GLP-1 receptor agonist therapy or never reach therapeutic doses. 

To test prevention under strongly emetogenic conditions, participants received a single 1mg dose of semaglutide without the gradual titration used in clinical practice. Any vomiting, the primary endpoint, occurred in 43.0% of participants receiving tradipitant (61 of 142) and 58.5% of those receiving placebo (96 of 164), a 27% relative reduction. The key secondary endpoint, vomiting with a worst nausea score of 3 or higher, occurred in 33.1% and 50.6%, respectively, a 35% relative reduction. Vanda reported that both differences were statistically significant.

Post hoc exploratory analyses of higher-burden vomiting found frequent vomiting, defined as more than 2 episodes on more than one day, in 6.3% of the tradipitant group and 15.9% of the placebo group, and extreme vomiting (more than 10 total episodes) in 2.8% and 14.6%, respectively. Nearly all vomiting occurred within the first 2 days, with the widest gap between groups on days 1 and 2. Vanda said tradipitant was generally well tolerated, with no new safety signals.

The results were announced in a company press release, which did not report confidence intervals or detailed adverse event data. Vanda said a pooled exposure-response analysis of phase 2 and phase 3 data supports extrapolating the effect to real-world semaglutide dosing. The company plans to discuss the results with the FDA and intends to submit a supplemental new drug application for the prevention of vomiting associated with GLP-1 receptor agonist therapy.

Source: Vanda Pharmaceuticals. Vanda Pharmaceuticals announces positive results from Study 3601 of Nereus (tradipitant) for prevention of GLP-1-induced vomiting. Press release. Vanda Pharmaceuticals; October 27, 2026. Accessed October 28, 2026.