Vanda Pharmaceuticals announced positive topline results from a Phase 2 randomized controlled trial demonstrating that tradipitant, an oral neurokinin-1 (NK-1) receptor antagonist, significantly reduced gastrointestinal side effects associated with GLP-1 receptor agonist therapy for obesity. The investigational drug achieved a 50% relative reduction in vomiting compared to placebo when administered alongside semaglutide.
Trial Design and Primary Results
The Phase 2 study (VP-VLY-686-2601) enrolled 116 overweight or obese adults with body mass index between 25-40 kg/m² who had no prior GLP-1 exposure. Participants were pretreated with either tradipitant 85 mg twice daily or placebo for one week before receiving a 1 mg dose of semaglutide (Wegovy), a dose that typically requires 9 weeks of titration under current prescribing guidelines.
The study met its primary endpoint, with vomiting occurring in 29.3% of participants treated with tradipitant (17/58) compared with 58.6% who received placebo (34/58) (P=0.002). The key secondary endpoint, defined as vomiting plus worst nausea (3 or greater on a 0-5 scale), was reported in 22.4% of tradipitant recipients (13/58) versus 48.3% taking placebo (28/58) (P=0.004).
Addressing Treatment Discontinuation
The results address a significant clinical challenge in GLP-1 therapy, where real-world discontinuation rates reach 30-50% due to gastrointestinal side effects, often before patients achieve therapeutic doses. According to Mihael H. Polymeropoulos, MD, President, CEO and Chairman of Vanda, "Tradipitant's effect in reducing nausea and vomiting could significantly improve GLP-1 agonist adherence enabling more people to receive the full therapeutic benefit."
Real-world data demonstrates the consequences of early discontinuation. In a large retrospective cohort study of nearly 8,000 adults with overweight or obesity, participants who discontinued semaglutide early lost only 3.6% of their weight, compared to 10.9% among those who continued treatment. For tirzepatide, early discontinuation resulted in 3.6% weight loss versus 15.3% for those who persisted. Overall, individuals lost an average of 8.7% of baseline body weight after 1 year of treatment, compared to the 14.9% to 20.9% weight reductions demonstrated in phase 3 clinical trials.
Safety Profile and Previous Data
Tradipitant demonstrated a favorable safety profile consistent with previous studies, with no new safety signals observed. The efficacy findings align with previous data from motion sickness studies, where tradipitant reduced vomiting by more than 50% across randomized trials including more than 800 participants.
Market Positioning and Development Timeline
The results position tradipitant as a potentially transformative adjunct in the rapidly expanding global GLP-1 agonist market, which exceeded $50 billion through the first nine months of 2025. Early discontinuations due to gastrointestinal side effects impose substantial costs on both patients and payors, as patients forgo meaningful weight loss and reductions in complications like diabetes progression and cardiovascular events.
Vanda plans to advance tradipitant into Phase 3 trials in the first half of 2026 and will evaluate regulatory pathways for its use as an adjunct to GLP-1 therapy. Tradipitant, which is licensed from Eli Lilly and Company, is also under FDA review for motion sickness with a PDUFA date of December 30, 2025.
