Vanda Pharmaceuticals’ expansion into the booming GLP-1 market has cleared a midphase test. With the trial linking tradipitant to reduced nausea and vomiting in Wegovy patients, the biotech is gearing up to start a phase 3 trial in the setting in the first half of next year.
An FDA approval decision on tradipitant in motion sickness is due by Dec. 30. In parallel, Vanda is working to establish the oral neurokinin-1 receptor antagonist in the prevention of another cause of nausea and vomiting.
Patients on GLP-1 medicines for weight loss and diabetes often experience gastrointestinal side effects. And, with the GLP-1 market going gangbusters, the adverse events are affecting vast numbers of patients.
Vanda assessed the potential for tradipitant to help those patients in a phase 2 study. Participants took tradipitant or placebo twice a day for one week. After the pretreatment period, all patients received a 1-mg injection of Wegovy, one of Novo Nordisk’s GLP-1 drugs, and continued on tradipitant or placebo for another week.
In the tradipitant arm, 17 of 58 patients experienced vomiting after receiving Wegovy. The rate of vomiting was significantly lower than in the placebo cohort, where 34 of 58 patients had the adverse event. The vomiting results caused the trial to hit its primary endpoint. Tradipitant also had an edge over placebo on a secondary endpoint that looked at patients with vomiting and at least moderate nausea.
Novo and Eli Lilly, the leader in the GLP-1 space, have managed the propensity for patients to experience vomiting and nausea on their drugs by gradually increasing the dose. Patients start on a 0.25-mg dose of Wegovy and typically reach 1 mg—the dose Vanda used—after nine weeks.
Even so, 44% of people on Wegovy experienced (PDF) nausea in a phase 3 study. Almost 2% of patients stopped treatment because of nausea. Vomiting was a rarer adverse event, affecting 24% of people and driving 1.2% of discontinuations, but is still a barrier to patients reaching and staying on optimal doses. Vanda CEO Mihael Polymeropoulos, M.D., outlined the opportunities behind those figures.
“We know that GLP-1 analogs have to be titrated slowly because of the very frequent nausea and vomiting side effects, which actually limits the efficacy at least for a certain period of time,” the CEO said on an earnings call late last month. “A number of patients, around 15% or so, may actually drop out of treatment.”
Vanda shares rose 17% to $5.15 in early trading after the data were released.
Tradipitant has been marred by controversy. Last month, Vanda, in collaboration with the agency, halted or dropped multiple lawsuits it had filed against the FDA surrounding the drug, including one over a partial hold blocking the company from conducting long-term clinical studies of tradipitant in motion sickness.
The company has also paused a legal battle over a 2024 FDA rejection of tradipitant as a gastroparesis treatment.