High-dose semaglutide ramps up weight loss, says Novo
A trial exploring the use of a higher dose of Novo Nordisk's GLP-1 agonist semaglutide has shown that patients with obesity who were taking the drug were able to shed more than a fifth of their body weight.
The phase 3b STEP UP trial in more than 1,400 patients compared a 7.2mg weekly subcutaneous injection of semaglutide to the standard 2.6mg weekly dose sold as Wegovy or a matched placebo.
Among those who adhered to treatment, the high-dose group achieved an average weight loss of 20.7%, compared to 17.5% with the lower dose and 2.4% in the placebo group. For the overall group, including those who may have missed doses, the reduction was 18.7% with the high dose, 15.6% with the low dose, and 3.9% with placebo.
The increase in weight loss with the higher dose was impressive, but still lower than has been achieved in clinical trials of Eli Lilly's rival obesity therapy Zepbound (tirzepatide), which helped patients shed 20.9% of their weight at the same 72-week time point in its pivotal trial.
Martin Holst Lange, Novo Nordisk's head of development, said that the safety and tolerability of the two doses of semaglutide were comparable, while around a third of patients treated with 7.2mg achieved more than 25% weight loss.
"Results from STEP UP further strengthen the clinical profile of semaglutide for the treatment of obesity, in addition to the health benefits already established with Wegovy, including cardiovascular risk reduction," he added.
It remains to be seen whether the data will help Novo Nordisk in its tussle for market share in the obesity market with Lilly, which reported head-to-head data in December showing that Zepbound was 47% more effective than the current dose of Wegovy.
Shares in Novo Nordisk fell sharply after the announcement. However, that was likely driven by news that Wegovy and two other semaglutide products – Ozempic and Rybelsus for type 2 diabetes – have been included on the list of the next 15 drugs to be subject to what the government calls price negotiation and the industry calls price setting under the Inflation Reduction Act.
Tirzepatide will be protected from inclusion in the negotiation list until 2030, as it was first approved in 2022, while semaglutide has been on the market since 2017.
There was no word from Novo Nordisk on plans to file the high-dose version for approval, which clearly cuts the efficacy deficit with its main rival, although, the company said it would present the data in full at a scientific conference later this year.
It has other candidates in its late-stage obesity pipeline, headed by CagriSema, which combines dual amylin and calcitonin receptor agonist cagrilintide with semaglutide. Phase 3 results reported for CagriSema last month were a disappointment, however, with a 20.4% reduction in weight in the REDEFINE 1 study over 68 weeks that fell short of Novo Nordisk's hope of a 25% loss.
At the least, the new 7.2mg results point to scope for hiking the semaglutide dose in CagriSema to chase down that weight-loss target.
The company is also running a phase 3b trial of 7.2mg semaglutide in more than 500 patients with obesity and diabetes – STEP UP T2D – with data due in the next few months.
