The Phase 3 study is evaluating two doses of Novo’s Wegovy pill in people with obesity or overweight in combination with a reduced-calorie diet and increased physical activity.
Novo Nordisk has begun a placebo-controlled trial in search of “the most optimal lower dose” for its oral GLP-1 medicine for weight loss.
The trial will test two different, undisclosed oral doses of GLP-1 receptor agonist semaglutide. Under the current Wegovy pill label, Novo advises patients to start on a 1.5-mg daily dose, spend 30 days on two intermediate doses and reach the 25-mg maintenance dose on day 91 days of treatment. The OASIS 5 trial, which began enrolling patients this month, could inform new dosing recommendations.
Novo is studying the lower maintenance doses “to fully reflect the patients’ needs in real-world obesity management,” a spokesperson told BioSpace via email. Establishing a broader range of maintenance doses “could provide greater flexibility in treatment and optimizing the patient experience,” the Novo spokesperson added.
The company has yet to disclose which doses it is testing in OASIS 5. Novo sells 1.5-mg, 4-mg, 9-mg and 25-mg doses of semaglutide as its Wegovy pill. The drugmaker also sells oral semaglutide doses of 3 mg, 7 mg and 14 mg in diabetes under its Rybelsus brand.
On an earnings call this month, Jamey Millar, executive vice president, U.S. operations at Novo, said that while a 1.5-mg dose is available, “many patients start on the 4-mg strength.” Novo increasingly considers both doses to calculate new patient starts, Millar said.
There is limited evidence of the effect of low doses of semaglutide on people with obesity or overweight. Novo studied doses of 25 mg and 50 mg for weight loss in people without type 2 diabetes in OASIS 4 and OASIS 1, respectively. The company’s PIONEER 1 and PIONEER 4 trials tested doses of 7 mg and 14 mg in people with type 2 diabetes, primarily to assess semaglutide’s effect on blood sugar.
At week 52 of PIONEER 4, 16% of patients receiving oral semaglutide had lost at least 10% of their body weight, compared to 63% of participants by week 64 of OASIS 4. However, differences between the patient populations confound comparisons of the data, making it unclear how much of the increased efficacy seen in OASIS 4 is attributable to the higher dose.
Marketing a lower-dose Wegovy pill could help Novo make the product more profitable. Patients taking injectable Wegovy use up to 7.2 mg of semaglutide a week. Patients on oral Wegovy take up to 25 mg of semaglutide a day. The gross margin on oral Wegovy is below that of the injectable, Novo CFO Karsten Knudsen said on an earnings call in February.
Analysts have identified the need to make large quantities of semaglutide as a possible weakness of oral Wegovy. Eli Lilly’s oral GLP-1 drug Foundayo is a small molecule, a class of medicines that are cheaper to manufacture than peptides such as semaglutide. “Lilly will be able to better compete with oral Wegovy on price points given the high margins of a small-molecule therapy,” Truist Securities analyst Srikripa Devarakonda recently told BioSpace.
Despite that, Wegovy pill has outsold Foundayo to date. Sales of the Wegovy pill, which beat Foundayo to market, ramped up faster than those of its rival, and Novo maintained the advantage over the first half of the year. Analysts have attributed Novo’s early lead to an apparent efficacy edge—though no head-to-head study of the oral options has been conducted—and to the name recognition of the Wegovy pill.
