Vanda Pharmaceuticals Inc. announced the initiation of Thetis, a clinical trial evaluating NEREUS (tradipitant) for the prevention of vomiting in patients receiving glucagon-like peptide-1 (GLP-1) receptor agonist therapies. NEREUS was recently approved for the prevention of vomiting induced by motion. GLP-1 receptor agonists, including semaglutide and tirzepatide, have transformed the treatment of type 2 diabetes and obesity.
However, gastrointestinal side effects, particularly nausea and vomiting, remain a significant challenge for many patients and are a leading cause of treatment discontinuation or dose reduction. Recent studies and approvals in the GLP-1 space further underscore this. Last month, a high dose of Wegovy was approved by the U.S. Food and Drug Administration (FDA) on the basis of providing additional weight-loss benefits, yet it comes with the tradeoff that the top two reported adverse effects of nausea and vomiting for this high dose are of increased frequency compared to the previously approved Wegovy maximum dose.
The Thetis study is a multicenter, randomized, double-blind, placebo-controlled trial that will evaluate the efficacy and safety of oral tradipitant in patients initiated at a high dose of a GLP-1 receptor agonist. The primary endpoint is the proportion of patients free from vomiting episodes during the treatment period. The Phase 2 study, as previously announced in Vanda's press release dated November 15, 2025, was similar in design where patients were pre-treated with either tradipitant or placebo before administering a 1 mg injection of Wegovy, a dose that normally takes 9 weeks of titration to reach.
The phase 2 study succeeded and met its primary endpoint, with only 29.3% of tradipitant-treated participants (17/58) experiencing vomiting compared to 58.6% on placebo (34/58) (p=0.0016), representing a 50% relative reduction. The study also met the key secondary endpoint of the proportion of participants with vomiting and significant nausea at 22.4% in the tradipitant group (13/58) versus 48.3% on placebo (28/58) (p=0.0039). Vanda expects topline results from the Thetis study by Fourth Quarter 2026.
Following completion of the Thetis study, additional study data may be required prior to approval of a New Drug Application (NDA). NEREUS (tradipitant) is a neurokinin-1 receptor antagonist licensed by Vanda from Eli Lilly and Company. NEREUS is approved for the acute prevention of vomiting induced by motion in adults, and is currently in clinical development for a variety of indications, including gastroparesis and the prevention of nausea and vomiting induced by GLP-1 receptor agonists.
