Novo Nordisk, Lilly highlight oral obesity drugs at ADA

New data from Novo Nordisk’s phase 3 trial of an oral, high-dose formulation of semaglutide reinforces its potential as a weight-loss therapy in obesity, but Eli Lilly is in hot pursuit.

The 50 mg oral semaglutide pill achieved a 15.1% weight loss in the phase 3 OASIS study involving patients who were overweight or obese, but who did not have diabetes, with the results simultaneously presented at the American Diabetes Association (ADA) over the weekend and published in The Lancet.

Oral semaglutide is already sold as Rybelsus in a 14 mg formulation for the treatment of type 2 diabetes, bringing in sales of $1.6 billion last year, but extending its use into non-diabetic obesity could unlock an even larger market for the drug.

A once-weekly injectable form of the drug is sold as Wegovy and has also seen strong uptake since launch, albeit hampered by production capacity constraints, with sales of $666 million in the first quarter of this year.

“Having an oral formulation of semaglutide in addition to the subcutaneous [...] formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” said Professor Filip Knop of Gentofte Hospital, University of Copenhagen, who presented the results at ADA.

“The weight loss also led to improvements in physical functioning, allowing participants to have an improved quality of life for everyday activities,” he added.

In OASIS 1, a significantly higher number of patients taking oral semaglutide were able to achieve a weight loss of 5% or more compared to placebo, at 85% versus 26%, respectively, which was another primary endpoint of the study.

Two-thirds (69%) of semaglutide-treated patients lost 10% of their body weight, compared to 12% of the placebo arm. Similarly, a third (34%) of them lost 20%, compared to 3% of controls.

The data put Novo Nordisk on course to bring the first oral GLP-1 agonist to market for obesity, building on its lead in injectables with Wegovy, but competition is looming on both fronts.

Lilly’s oral GLP-1 challenger

Lilly’s dual GIP/GLP-1 agonist Mounjaro (tirzepatide) is expected to mount a strong challenge in the injectables category if it gets approved by regulators later this year, and at ADA the drugmaker also reported mid-stage results with its oral candidate orforglipron, a non-peptide GLP-1 agonist.

The study – published in the New England Journal of Medicine – revealed a 14.7% reduction in body weight with orforglipron in patients with type 2 diabetes who were overweight or obese, a strong finding, given that GLP-1 drugs have generally been shown to be less effective at reducing weight in diabetics.

It was a dose-ranging study, and the range of weight loss seen with Lilly’s drug was 9.4% to 14.7% at 36 weeks, compared to 2.3% with placebo. The company is now running phase 3 trials of the drug in both diabetic (ACHIEVE) and non-diabetic (ATTAIN) overweight and obese patient populations, with results due in 2025.

Boehringer/Zealand injectable

Meanwhile, data on another potential rival in the injectable obesity category from Boehringer Ingelheim and Zealand Pharma was also presented at ADA.

46 weeks of treatment with their dual glucagon/GLP1 agonist survodutide (BI 456906) given as a weekly subcutaneous injection resulted in up to 18.7% weight loss in overweight or obese individuals at the highest dose tested (4.8 mg).

Overall, 40% of people who reached the highest two doses of survodutide (3.6 mg and 4.8 mg) achieved a weight loss of at least 20%, versus 0% with placebo. Furthermore, 15% or more weight loss was achieved by 67% of people who reached survodutide 4.8 mg versus 4.3% of controls.

There was one red flag in the data, however; namely, that around a quarter (24.6%) of patients taking the highest dose discontinued treatment, compared to 4% of the placebo group. The discontinuations mainly occurred during a dose-escalation phase in which injections were given twice a week and could be addressed with a gentler ramp-up, according to the partners.

Phase 3 trials of survodutide are in the planning stages, subject to discussion with regulatory authorities, according to the drug’s developers.