A phase 3 trial of Boehringer Ingelheim’s survodutide in people with obesity and Type 2 diabetes has met its co-primary endpoints. Yet, with the readout echoing earlier data that underwhelmed analysts, shares in Boehringer’s partner Zealand Pharma fell 12% in early trading in Denmark.
The data, which researchers presented at the Annual Meeting of the European Association for the Study of Diabetes in Milan, come from the Synchronize-2 study. Investigators randomized 755 adults to receive weekly injections of placebo or one of two doses of survodutide, a glucagon/GLP-1 receptor dual agonist. At Week 76, Boehringer reported mean weight loss of 13.1% on the high dose of survodutide.
With people on placebo losing 3.1% of their body weight, the survodutide result was strong enough for the trial to meet one of its co-primary endpoints. The trial hit its other co-primary endpoint because 79.3% of people on survodutide lost at least 5% of their weight, versus 32.7% in the placebo arm.
Boehringer generated the data in analyses representing the hypothetical treatment effect expected if all participants adhered to the assigned trial regimen. However, a report in the New England Journal of Medicine (NEJM) took a different approach to the primary efficacy assessment. In those analyses, mean weight loss on placebo and the high dose of survodutide were 3.9% and 9.8%, respectively.
In both types of analysis, weight loss on survodutide fell short of the level seen in Synchronize-1. That was expected—Synchronize-1 excluded Type 2 diabetes patients, which typically leads to higher weight loss—but means Boehringer continues to face the concerns raised by the earlier readout.
In a note to investors back in June, BMO Capital Markets analysts said survodutide showed “a less competitive profile vs other agents” in Synchronize-1. Given the data, “it could be more difficult for Zealand/BI to find a competitive foothold in today's rapidly evolving obesity/metabolic market,” the analysts added.
Those concerns reflected undifferentiated efficacy, plus tolerability issues. In Synchronize-1, 45% of people on the high dose of survodutide had vomiting and 25% discontinued treatment following an adverse event. The Synchronize-2 data are similar, with 26% of people discontinuing after an adverse event and 39% experiencing vomiting. Strict dose escalation may have driven the figures up, the NEJM authors suggested.
Synchronize-2 met its secondary blood sugar endpoint, but the 1.21% decline in HbA1c is unexceptional in a competitive sector. Boehringer also highlighted data on waist circumference and insulin sensitivity to make the case that survodutide could improve metabolic health.
Shares in Zealand, which licensed the asset to Boehringer, had fallen 11% to 241 Danish kroner by 12.50pm local time on Thursday. Boehringer is solely responsible for development and commercialization globally. Zealand is eligible to receive up to 315 million euros ($355 million) in milestones.
With doubts over survodutide's competitiveness in weight loss looming over the drug all year, one area where Boehringer has retained hopes is the therapy's effect on the liver. A pre-specified analysis of Synchronize-1 back in June found patients on survodutide charted liver fat reductions of up to 63.1%, compared to 25% in the study’s control cohort.