Boehringer/Zealand dual-acting drug causes 16.6% weight loss

Results from a late-stage trial of Boehringer Ingelheim and Zealand Pharma's GLP-1 and glucagon agonist drug survodutide suggest it is on track to challenge Novo Nordisk and Eli Lilly, which currently dominate the weight-loss market.

The phase 3 SYNCHRONIZE-1 – conducted in people with obesity or overweight but without type 2 diabetes – revealed a 16.6% reduction in body weight after 76 weeks with a once-weekly injection of survodutide, compared to a 3.2% drop with placebo.

However, the two companies think there is an underlying difference between survodutide and current drugs that could set it apart if it reaches the market. They reckon that targeting glucagon alongside GLP-1 results in a more nuanced reduction in body fat, specifically an improved reduction in visceral fat around organs that is known to lead to metabolic dysfunction and is closely connected to impaired liver function.

Patients treated with survodutide in SYNCHRONIZE-1 saw a statistically significant reduction in waist circumference that points to a reduction in visceral fat, according to the companies, which plan to present the full results from the trial at the American Diabetes Association (ADA) annual congress in July.

The trial also met its other main endpoint, with 85.1% of survodutide-treated patients achieving at least 5% body weight reduction versus 38.8% of the placebo arm.

"There is an urgent need for new therapies that go beyond weight reduction alone to support meaningful improvements in metabolic health," said the trial's co-ordinating investigator, Prof Carel Le Roux of University College in Dublin, Ireland.

"Survodutide's dual agonism is particularly exciting, as it offers a promising approach to addressing this significant unmet need in care," he added.

There's no word yet from Boehringer and Zealand Pharma on their timeline for filing survodutide for approval, but they suggested the drug has a chance of becoming the first dual GLP-1/glucagon agonist to reach the market. Additional trials from the phase 3 SYNCHRONIZE programme in obesity/overweight are due to read out this year.

Meanwhile, two late-stage studies (LIVERAGE and LIVERAGE-Cirrhosis) are also underway in metabolic dysfunction-associated steatohepatitis (MASH), a fatty liver disorder characterised by inflammation and liver damage that is closely linked to obesity.

Stimulating glucagon increases energy expenditure in the body and has a direct impact on the liver, while preliminary studies suggest it can also lead to an improvement of fibrosis (scarring), which is another consequence of MASH.

If the clinical programme delivers positive results, the drug could be an option for more than a billion people living with obesity and MASH worldwide, according to Boehringer, which licensed global development and commercialisation rights to the drug in an alliance stretching back to 2011.

If it reaches the market, survodutide will have to break into an obesity market dominated by Novo Nordisk's GLP-1 agonist Wegovy (semaglutide) and Lilly's dual GIP/GLP-1 agonist Zepbound (tirzepatide), both also delivered as once-weekly injections, and starting to evolve with the launch of a pill formulation of Wegovy and Lilly's oral GLP-1 drug Foundayo (orforglipron).

Other glucagon-directed medicines are also coming through the industry pipeline, meanwhile, including Lilly's triple therapy retatrutide – targeting GLP-1, GIP, and glucagon – which achieved weight losses of up to 28.7% in its first phase 3 readout, Novo Nordisk's triple-acting UBT251, and Innovent Biologics' glucagon/GLP-1 agonist mazdutide.

Boehringer is also developing its own triple, targeting GLP-1, GIP, and NPY2, which is being prepared for phase 2 in the middle of this year.

Under the terms of the deal with Boehringer, Zealand is eligible for high single to low double-digit percentage royalties on global sales of survodutide and up to €315 million in outstanding milestone payments.

Shares in Zealand Pharma rose around 7% on the Nasdaq Copenhagen stock exchange after the announcement. Boehringer is privately held.