Weight Loss of 15% with Oral Semaglutide 50 mg Equal to SQ Wegovy: Late Stage Clinical Trial

Novo Nordisk on May 22 announced topline results of a phase 3 clinical trial that showed once-daily oral semaglutide 50 mg was associated with weight loss of 15% among individual with obesity or overweight and one or more related comorbidity.

The weight loss seen in the 68-week OASIS 1 trial is similar to that seen in the STEP 1 trial with the subcutaneous 2.4 mg formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), marketed as Wegovy.

”The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk, in the company announcement.

In OASIS 1, researchers enrolled 667 adults with overweight or obesity (BMI ≥ 27.0 kg/m²) and ≥1 weight-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) or BMI ≥ 30.0 kg/m² who had a history of at least one self-reported unsuccessful dietary effort to reduce body weight. The 2 primary outcome measures were percentage change in body weight at 68 weeks as well as number of participants achieving body weight reduction of ≥5%. A mean baseline bodyweight of 105.4 kg was recorded.

When evaluating the effects of treatment based on the trial product estimand, study participants treated with oral semaglutide 50 mg achieved a statistically significant weight loss of 17.4% after 68 weeks compared to a reduction of 1.8% among those receiving placebo. Further, the majority (89.2%) of semaglutide-treated participants reached the weight loss of ≥5% after 68 weeks, compared to 24.5% placebo-treated participants.

When applying the treatment policy estimand, researchers reported superior weight loss of 15.1% among those treated with oral semaglutide 50 mg compared to a reduction of 2.4% in the placebo group. Once again, the majority of participants in the treatment group (84.9%) lost ≥5% of baseline body weight after 68 weeks, compared to 25.8% of participants in the placebo group.

Oral semaglutide 50 mg appeared both safe and well-tolerated in the trial, according to Novo Nordisk. The most common adverse events, prominent during dose escalation, were gastrointestinal and were reported as mild to moderate, diminishing over time and consistent with the GLP-1 RA class.

The OASIS phase 3 clinical development program comprises 4 trials evaluating the safety and efficacy of once-daily oral semaglutide 25 mg and 50 mg in obesity. The program has enrolled approximately 1300 adults with obesity or overweight with one or more comorbidities.

Filing for regulatory approval in the US and EU is expected this year, the company said.

Demand for the injectable sematglutide 2.4 mg Wegovy has caused signficant supply problems for the drug maker leading the company most recently to pause all mareting and promotional efforts.