Tradipitant GLP 1 vomiting trial reports 27 percent relative drop in Phase 3

Vanda Pharmaceuticals said on 27 October 2026 that its tradipitant GLP 1 vomiting trial met its main goal in adults given semaglutide without the usual slow dose increase. In the Phase 3 study, 43.0% of people on Nereus, the brand name for tradipitant, vomited against 58.5% on placebo, a 27% relative reduction, the company reported. Vanda plans to discuss the data with the FDA and file a supplemental application. The results come from a company press release and have not appeared in a journal.

What Study 3601 found

Study 3601 was a randomised, placebo controlled Phase 3 trial, according to the Vanda press release. Results cover 306 participants: 142 took Nereus and 164 took placebo. The release does not explain why the two groups differ in size. The primary endpoint was the share of people with any vomiting. That figure was 43.0% with Nereus (61 of 142) and 58.5% with placebo (96 of 164), with a site adjusted p value of 0.006. The key secondary endpoint combined vomiting with worst nausea scored 3 or higher on the study scale. It occurred in 33.1% of the Nereus group and 50.6% of the placebo group, a 35% relative reduction. Vanda said both endpoints were met. The trial therefore hit its two prespecified goals, the company said.

Vanda also reported two exploratory measures. Frequent vomiting, defined as more than two episodes on more than one day, hit 6.3% of people on Nereus and 15.9% on placebo. Extreme vomiting, meaning more than ten episodes in total, hit 2.8% and 14.6%. The company put the relative reductions at 60% and 81%. Vanda described both analyses as post hoc, meaning they were chosen after the data were in. Such results support a finding but cannot confirm it. Relative figures also sound larger than absolute ones, a point covered in our guide on how to read a trial headline. In absolute terms, 15.5 percentage points separated the two groups on the main endpoint of the tradipitant GLP 1 vomiting trial.

A trial built to provoke semaglutide nausea and vomiting

The design aimed for a strong trigger. Participants received one injection of semaglutide at full strength, with no gradual titration, the company said. Vanda used the same dose in its Phase 2 work and says that dose normally takes about nine weeks of step ups to reach. The approach makes semaglutide nausea and vomiting far more likely than in routine care, which gives an anti nausea drug a hard test. Almost all vomiting in both groups happened by day two, Vanda reported. Rates peaked on day one, and the gap between Nereus and placebo was widest on days one and two. Few new cases began after day two. Vanda said this points to dosing before a GLP 1 drug is started or raised.

Vomiting on placebo was almost identical across the two studies, but more people on Nereus vomited in Phase 3 than in Phase 2.

The Phase 3 effect was smaller than the earlier one. In Study 2601, Vanda gave the drug or placebo to 116 adults with overweight or obesity before the same semaglutide challenge. According to its Phase 2 topline release, 29.3% on tradipitant vomited against 58.6% on placebo, a 50% relative reduction. Vomiting on placebo was almost identical across the two studies, but more people on Nereus vomited in Phase 3 than in Phase 2. The relative cut fell from 50% to 27% as the trial grew. Larger trials often give a more modest estimate than small early studies. Vanda said a similar drop of about 80% in extreme vomiting appeared in Phase 2. The company did not report the Phase 2 frequent vomiting figure in the new release.

Why GLP 1 side effects matter for Nereus

Vanda's case rests on GLP 1 side effects and quitting. The company said nausea and vomiting are among the most common reasons people stop GLP 1 drugs or never reach a full dose. It cited real world studies in which roughly half of patients stopped therapy within one year, with stomach problems among the leading causes. Other peptide drugs face the same hurdle. In one recent amylin trial, nausea was the main side effect of the new peptide. "These results demonstrate that NEREUS can meaningfully reduce vomiting and frequent multi-day vomiting induced by GLP-1 therapy, which are key contributors to treatment discontinuation," said Mihael Polymeropoulos, Vanda's president, chief executive and chairman. The trial itself did not measure whether people stayed on treatment longer.

Nereus is a small molecule, not a peptide. It is an NK1 receptor antagonist that blocks substance P signalling in the brain's vomiting centre, including the area postrema and the nucleus tractus solitarius, Vanda said. The company said it expects the drug to work across all GLP 1 receptor agonists, but Study 3601 tested only semaglutide. The FDA approved Nereus in December 2025 to prevent vomiting caused by motion. It is not approved for vomiting linked to GLP 1 drugs, and the trial does not set out a regimen for everyday care. People on weight loss or diabetes drugs who struggle with nausea should raise it with their prescriber. This report is research news, not medical advice, and no one should change treatment based on a press release.

Open questions before an sNDA filing

Several facts are missing. The release gives no baseline details on who took part, such as weight, diabetes status or sex. It gives no adverse event counts, saying only that Nereus was generally well tolerated with no new safety signals. A single full strength injection also differs from how people start semaglutide in practice. Vanda said a pooled exposure response analysis of its Phase 2 and Phase 3 data showed a stable effect across semaglutide levels, which it says supports use with real world dosing. That analysis has not been published for outside review. In April 2026 Vanda announced a trial named Thetis with a similar high dose start. The October release does not say whether Study 3601 is that trial.

Vanda said it will discuss the results with the FDA and plans a supplemental New Drug Application, or sNDA, to add prevention of GLP 1 related vomiting to the Nereus label. It gave no filing date for the tradipitant GLP 1 vomiting submission. The agency would then judge whether two studies built on a single provoking dose are enough to support the claim. Readers should watch for full data at a medical meeting or in a peer reviewed journal, complete safety tables and any study in people stepping up doses the usual way. Tolerability is now a theme across obesity drug trials, and a recent Lilly combination study saw more dropouts for side effects than with tirzepatide alone. Whether an add on pill changes that remains untested.

Conclusion

In the tradipitant GLP 1 vomiting trial, Vanda reports that Nereus reduced the share of people who vomited after a forced semaglutide dose, from 58.5% to 43.0%. The effect was smaller than in Phase 2, the strongest results come from post hoc analyses, and full safety data are not public. Vanda plans to talk to the FDA and file an sNDA. Any approval decision would rest on the agency's review, not on the company's release.