Oral GLP-1 contest ramps up with new Novo Nordisk data

Novo Nordisk has won a round on points in the oral obesity therapy fight, as phase 3 results of its pill formulation of GLP-1 agonist Wegovy reveal up to 16.6% weight loss.

The results come from the phase 3 OASIS 4 trial, published in the New England Journal of Medicine, which tested a 24 mg oral dose of semaglutide, the active ingredient in Wegovy, which has to be injected once a week.

In the 64-week study, patients who adhered to treatment with oral semaglutide achieved an average weight loss of 16.6%, compared to 2.7% in the placebo group, while the fall in those who took the pills intermittently was 13.6% and 2.2%, respectively.

That level of efficacy is very close to the weight loss achieved at that time point in trials of the current injectable form of Wegovy, around 17%. Moreover, the data seems to be quite a bit better than the results seen with oral semaglutide's closest rival – Eli Lilly's oral GLP-1 drug orforglipron – in the ATTAIN-1 study published earlier this week.

While comparing trials with different protocols can be misleading, ATTAIN-1 showed that people taking orforglipron's top dose (36 mg) lost 12.4% of their weight at 72 weeks, versus a 0.9% fall with placebo.

OASIS 4 also showed that over a third (34.4%) of patients adhering to oral semaglutide experienced weight loss of 20% or more, versus 2.9% for placebo. In ATTAIN-1, that threshold was passed in around a fifth of patients treated with the optimal dose of orforglipron.

Novo Nordisk is also ahead in the race to bring an oral GLP-1 to market for weight loss, as it has already filed semaglutide for FDA approval, with a decision before the end of this year, while Lilly has said it hopes to submit orforglipron to the US regulator in the fourth quarter.

The strong clinical data for oral semaglutide is a big win for Novo Nordisk, which has struggled to maintain its leadership in the obesity market in the face of pressure from Lilly's fast-growing GLP-1/GIP agonist Zepbound (tirzepatide), which outperformed Wegovy in head-to-head trials, as well as widespread selling of compounded versions of injectable semaglutide in the US.

Earlier this month, Novo Nordisk announced a plan to shed thousands of jobs and cut costs in an attempt to cut billions of dollars off its annual costs, after seeing its shares lose nearly two-thirds of their value since the start of the year.

If approved, oral Wegovy could tip the commercial balance back in Novo Nordisk's favour, helped by the strong efficacy, recognition of semaglutide among prescribers and patients, and patient preference for a convenient, daily oral option.

In a statement, Novo Nordisk's chief scientific officer Martin Holst Lange noted that less than 2% of people living with obesity are currently taking injectable weight-loss medication, pointing to a big opportunity for an oral alternative.

"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 overweight or living with obesity," he said.