Vanda Pharmaceuticals has launched 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-II 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 US 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.

"GLP-1 receptor agonists offer significant benefits, but vomiting and nausea can severely impact patient adherence and quality of life. NEREUS 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," said Mihael H Polymeropoulos, M.D., President, CEO and Chairman of the Board, Vanda Pharmaceuticals.

The Thetis study is a multicenter, randomised, 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-II study, as previously announced, 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 nine weeks of titration to reach. The phase-II study succeeded and met its primary endpoint, with only 29.3 percent of tradipitant-treated participants (17/58) experiencing vomiting compared to 58.6 percent on placebo (34/58) (p=0.0016), representing a 50 percent relative reduction. The study also met the key secondary endpoint of the proportion of participants with vomiting and significant nausea at 22.4 percent in the tradipitant group (13/58) versus 48.3 percent on placebo (28/58) (p=0.0039).