As reported on PharmaBiz, Vanda Pharmaceuticals has launched a new clinical trial, known as Thetis, to evaluate whether its neurokinin‑1 (NK‑1) receptor antagonist Nereus (tradipitant) can prevent vomiting associated with glucagon‑like peptide‑1 (GLP‑1) receptor agonist therapy. The study reflects growing efforts to improve tolerability of widely used metabolic drugs whose gastrointestinal side effects often limit long‑term use.
GLP‑1 receptor agonists such as semaglutide and tirzepatide have become cornerstones of treatment for type 2 diabetes and obesity, delivering substantial glycemic and weight‑loss benefits. Despite their efficacy, nausea and vomiting remain among the most common adverse effects and are a frequent reason for dose reductions or discontinuation. The challenge has been highlighted most recently by the US Food and Drug Administration’s approval of higher‑dose Wegovy, which provides increased weight loss but is associated with higher rates of gastrointestinal complaints, particularly nausea and vomiting.
Thetis is a multicenter, randomized, double‑blind, placebo‑controlled study designed to assess both the effectiveness and safety of oral tradipitant in patients starting GLP‑1 receptor agonists at higher doses. The primary endpoint is the proportion of participants who remain free from vomiting episodes during the treatment period. By focusing on patients exposed to higher‑intensity therapy, the study aims to reflect real‑world scenarios where side effects can be most problematic.
Confidence in the program is supported by earlier phase 2 findings. In that study, patients were pre‑treated with tradipitant or placebo before receiving a 1 mg injection of Wegovy, a dose that usually requires gradual titration. Tradipitant significantly reduced vomiting compared with placebo and also lowered the combined burden of vomiting with clinically significant nausea, demonstrating a meaningful improvement in gastrointestinal tolerability.
“Nausea and vomiting can significantly affect adherence and quality of life for patients on GLP‑1 therapies,” said Vanda president and CEO Mihael H. Polymeropoulos. He noted that tradipitant’s established antiemetic activity positions it as a potential solution to help patients remain on effective metabolic treatments.
Vanda expects topline results from the Thetis trial in the fourth quarter of 2026. Depending on the outcome, additional studies may be required before submission of a New Drug Application for this indication.
Tradipitant is licensed to Vanda from Eli Lilly and Company and is already approved for preventing motion‑induced vomiting in adults. Beyond the Thetis program, the drug remains in development for other gastrointestinal disorders, including gastroparesis.
