Bagsværd, Denmark, Plainsboro: Today, The New England Journal of Medicine published the results from the OASIS 4 phase 3 trial that studied the efficacy and safety of the investigational once-daily oral semaglutide 25 mg (Wegovy® in a pill*), marking a significant milestone in the company’s ambition to advance obesity care. In the 64-week trial, oral semaglutide 25 mg, alongside lifestyle modifications, was compared to placebo in 307 adults with obesity or overweight with one or more weight-related comorbidities, without diabetes.1
Results showed that if all participants adhered to treatment, average weight loss of 16.6% was achieved by people taking oral semaglutide 25 mg compared to 2.7% for placebo at 64 weeks, with over a third (34.4%) experiencing a weight loss of 20% or more, versus 2.9% for placebo.1**
This was comparable with previous trial results of injectable Wegovy®.3
When looking at the effect regardless of whether the participants took the medicine exactly as they should, people taking oral semaglutide 25 mg still achieved an average weight loss of 13.6% versus 2.2% with the placebo.1*** Close to a third (29.7%) had a weight loss of 20% or more versus 3.3% for placebo.1*** Additionally, the study also found that oral semaglutide 25 mg improved cardiovascular risk factors, as well as the ability to be more active in daily life, compared to placebo. This was consistent with previous trial results of injectable Wegovy®.1,3
“The oral semaglutide 25 mg data show compelling efficacy for an oral weight management medication with 16.6% weight loss and a safety and tolerability profile consistent with injectable Wegovy®,” said Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk. “Currently, less than 2% of individuals with obesity in the US receive obesity medication and Wegovy® in a pill may also address patient preference for oral treatment. Pending FDA approval, ample supply will be available to meet the expected US demand as we hope to set a new treatment benchmark for oral weight loss medications for people with overweight or obesity.”
The safety and tolerability profile of oral semaglutide was consistent with that for injectable Wegovy®.1,3 In the OASIS 4 trial, gastrointestinal adverse events with oral semaglutide 25 mg were generally mild to moderate in severity and transient; the most common of which were nausea (46.6% versus 18.6% for placebo) and vomiting (30.9% versus 5.9% for placebo).1 Adverse events leading to permanent treatment discontinuation were 6.9% (oral semaglutide 25 mg) and 5.9% (placebo). The incidence of serious adverse events was 3.9% (oral semaglutide 25 mg) and 8.8% (placebo).1 This reinforces the safety and tolerability profile of semaglutide, as also demonstrated in more than 37 million patient-years of exposure.1,4
“The OASIS 4 trial results further underscore the significant impact that semaglutide can have in achieving sustainable weight loss and broader health benefits,” said Sean Wharton, lead study author and medical director of the Wharton Medical Clinic. “Oral semaglutide 25 mg builds on the proven efficacy and established safety and tolerability profile of semaglutide and represents a significant advancement in obesity treatment. People with overweight or obesity have individual preferences, and with oral semaglutide as a potential new treatment option, more of those who are not on treatment today may consider starting GLP-1 treatment.”
In February, Novo Nordisk submitted a New Drug Application (NDA) for the once-daily pill formulation of Wegovy®.2* The FDA review of this NDA is anticipated to be completed by the end of this year.5 Currently, there are no approved oral formulations of a GLP-1 medicine for weight loss.
If approved by the FDA, the pill for weight management will be fully made in the US, with production already underway at Novo Nordisk’s significantly expanded manufacturing facility.
* Tradename of ‘Wegovy® pill’ submitted to the FDA and is pending approval.
** Based on the trial product estimand: estimated treatment effect if all participants adhered to treatment.
*** Based on the treatment policy estimand: treatment effect regardless of treatment adherence.
OASIS 4 was a 64-week phase 3 randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of once-daily oral semaglutide 25 mg versus placebo in 307 adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with one or more weight-related comorbidities.1 People with diabetes were excluded.1 OASIS 4 included a 64-week treatment period, including a 12-week dose escalation, and a 7-week off-treatment follow-up period.1
In total, 307 participants were randomised in a 2:1 ratio to once-daily oral semaglutide 25 mg or placebo, alongside lifestyle intervention for 64 weeks.1
Oral semaglutide 25 mg (Wegovy® in a pill*) is not approved in the US or in Europe.
