Vanda Pharmaceuticals Initiates Thetis Trial Testing NEREUS for GLP-1 Receptor Agonist-Induced Vomiting
Key Insights
Vanda Pharmaceuticals has launched the Thetis study, a Phase 2 clinical trial evaluating NEREUS (search) (tradipitant) for preventing vomiting (search) in patients receiving high-dose GLP-1 receptor (search) agonist therapies.
A previous Phase 2 study demonstrated that tradipitant reduced vomiting (search) by 50% compared to placebo, with only 29.3% of treated patients experiencing vomiting versus 58.6% on placebo.
The trial addresses a significant clinical need as gastrointestinal side effects remain a leading cause of treatment discontinuation for GLP-1 therapies like semaglutide and tirzepatide.
Vanda Pharmaceuticals Inc. has initiated the Thetis study, a clinical trial evaluating NEREUS (search) (tradipitant) for the prevention of vomiting (search) in patients receiving glucagon-like peptide-1 (GLP-1) receptor agonist therapies. The announcement comes as gastrointestinal side effects continue to pose significant challenges for patients using these transformative diabetes and obesity (search) treatments.
Clinical Need for Antiemetic Solutions
GLP-1 receptor (search) agonists, including semaglutide and tirzepatide, have revolutionized the treatment of type 2 diabetes (search) and obesity (search). However, gastrointestinal side effects, particularly nausea (search) and vomiting (search), remain a significant challenge for many patients and are a leading cause of treatment discontinuation or dose reduction. The clinical urgency was highlighted by the recent FDA approval of a high-dose Wegovy formulation, which provides additional weight-loss benefits but comes with increased frequency of nausea and vomiting as the top two reported adverse effects compared to the previously approved maximum dose.
"GLP-1 receptor (search) agonists offer significant benefits, but vomiting (search) and nausea (search) can severely impact patient adherence and quality of life," said Mihael H. Polymeropoulos, M.D., President CEO and Chairman of the Board of Vanda Pharmaceuticals. "NEREUS (search) has demonstrated potent antiemetic effects in prior clinical studies. We are excited to advance this program, which has the potential to improve tolerability and allow more patients to fully benefit from these important therapies."
Trial Design and Previous Results
The Thetis study is designed as 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 (search) agonist. The primary endpoint is the proportion of patients free from vomiting (search) episodes during the treatment period.
The current trial builds on promising Phase 2 results announced in November 2025. In that study, patients were pre-treated with either tradipitant or placebo before administering a 1 mg injection of Wegovy, a dose that normally requires 9 weeks of titration to reach. The Phase 2 study met its primary endpoint, with only 29.3% of tradipitant-treated participants (17/58) experiencing vomiting (search) compared to 58.6% on placebo (34/58) (p=0.0016), representing a 50% relative reduction.
The study also achieved its key secondary endpoint, with the proportion of participants experiencing vomiting (search) and significant nausea (search) at 22.4% in the tradipitant group (13/58) versus 48.3% on placebo (28/58) (p=0.0039).
NEREUS Development Program
NEREUS (search) (tradipitant) is a neurokinin-1 receptor (search) antagonist licensed by Vanda from Eli Lilly and Company. The drug was recently approved for the acute prevention of vomiting (search) induced by motion in adults and is currently in clinical development for various indications, including gastroparesis (search) and the prevention of nausea (search) and vomiting induced by GLP-1 receptor (search) agonists.
Timeline and Regulatory Path
Vanda expects topline results from the Thetis study by Q4 2026. Following completion of the Thetis study, additional study data may be required prior to approval of a New Drug Application (NDA). The company's development strategy reflects the growing recognition that addressing gastrointestinal tolerability issues could significantly expand access to GLP-1 therapies for patients who might otherwise discontinue treatment due to side effects.