Competition in the oral obesity drug market is set to intensify after Eli Lilly's oral GLP-1 obesity treatment Foundayo (active ingredient: orforglipron) received U.S. FDA approval earlier this month, following the launch of Novo Nordisk's Wegovy tablet earlier this year. A new study also drew attention by showing that the Wegovy tablet demonstrated superior weight loss efficacy.
According to the pharmaceutical and biotech industry on Thursday, Novo Nordisk plans to present results of its "ORION" study — evaluating the weight loss efficacy and tolerability of semaglutide (Wegovy's active ingredient) versus orforglipron — at the Obesity Medicine Association annual meeting in San Diego on June 10 (local time).
The ORION study is a population-adjusted indirect treatment comparison (ITC) study comparing the efficacy and tolerability of oral semaglutide 25 mg (OASIS 4 data) and orforglipron 36 mg (ATTAIN-1 data) in adults with obesity or overweight without diabetes.
The orforglipron 17.2 mg tablet approved by the FDA on June 1 (local time) is equivalent to the 36 mg capsule used in the Phase 3 clinical trial and served as the comparator in the ORION study. Weight change from baseline was assessed using a simulated treatment comparison (STC) method, while tolerability outcomes were measured using a two-stage matching-adjusted indirect comparison (2SMAIC) method. The analysis included adjustments for baseline weight, glycemic status and sex.
According to the ORION study results, oral semaglutide 25 mg demonstrated significantly superior weight loss efficacy compared to orforglipron 36 mg.
The average difference in weight loss was 3.2 percentage points regardless of whether patients remained on treatment, and 3.0 percentage points when all patients continued treatment.
In addition, the likelihood of treatment discontinuation due to any adverse event was approximately four times higher with orforglipron than with semaglutide, and the likelihood of discontinuation due to gastrointestinal adverse events was approximately 14 times higher.
"This study strengthens the evidence supporting the clinical advantages of semaglutide," said Jamie Miller, senior vice president of U.S. operations at Novo Nordisk. "Since the product's approval, we have seen strong interest in Wegovy from healthcare professionals and patients seeking obesity treatment."
However, the researchers noted that despite adjusting for key baseline characteristics, other unidentified factors may remain, and differences in clinical trial protocols could also affect comparability. They cautioned that because the absolute number of adverse events was small, the magnitude of the differences should be interpreted with care.
"Patients frequently ask for comparative data between medications when making obesity treatment decisions," said Dr. Robert F. Kushner of Northwestern Feinberg School of Medicine. "In the absence of a head-to-head clinical trial comparing oral semaglutide and orforglipron for obesity treatment, the indirect treatment comparison from the ORION study provides important information that can be used in the shared decision-making process."