Despite meeting the primary endpoints in a Phase 3 trial, shares of Zealand Pharma dropped in premarket trading Thursday as the up to 9.8% weight loss reflected inferior loss to that generated by competitors.
Zealand Pharma shares dipped Thursday after its Boehringer Ingelheim-partnered glucagon/GLP-1 receptor dual agonist survodutide again delivered underwhelming weight loss results in a second Phase 3 trial.
While a press release shared by Boehringer on Thursday put the highest end of weight loss at 13.1% at 76 weeks based on efficacy estimand in the Phase 3 SYNCHRONIZE-2 trial, publication in The New England Journal of Medicine shows a reading of up to 9.8% weight reduction for participants taking the highest dose
—6 mg—of the candidate.
Efficacy estimand is the estimated treatment effect assuming patients remained on treatment for the duration of the study. The NEJM treatment regimen estimand measures efficacy regardless of regimen discontinuations or interruptions or whether other weight loss drugs were used.
Meanwhile, the companies said that patients given a lower 3.6 mg dose of survodutide saw a reduction in baseline weight of 8.2%, while those on placebo achieved 3.9% weight loss—a result the partners deemed statistically significant. The results were good enough to satisfy the study’s co-primary endpoints, which were percentage change in body weight from baseline and the proportion of participants who lost at least 5% of their weight; 79.3% of the 775 enrolled patients hit this target.
Shares of Zealand—from which Boehringer licensed survodutide in 2011—were down more than 8% to $248.50 on the Danish market on Thursday.
As for secondary measures, both high and low doses of survodutide reduced blood-glucose levels in study participants by 0.8% and 0.9% compared to 0.2% for placebo.
In terms of tolerability, around 18% of participants discontinued due to gastrointestinal adverse events—a well-known challenge with GLP-1 drugs—compared to 1.2% of placebo comparators. Most patients discontinued the trial in the dose escalation phase, Boehringer noted, “as the study protocol allowed limited flexibility to manage adverse events.”
The partners presented full results from SYNCHRONIZE-2 at the European Association for the Study of Diabetes (EASD) conference in Milan, Italy—where weight loss juggernaut Eli Lilly has largely stolen the show this week with candidates far exceeding the weight loss observed with Zealand and Boehringer’s candidate.
Boehringer and Zealand’s results follow a data disclosure from another Phase 3 trial— SYNCHRONIZE-1—in June. In this trial, patients saw up to 16.6% weight loss compared to 3.2% in the placebo arm at 76 weeks, a result Boehringer deemed statistically significant. The result left analysts unimpressed, with BMO Capital Markets writing in a June 7 note that survodutide “demonstrated a less competitive profile vs other agents.”
“We think it could be more difficult for Zealand/BI to find a competitive foothold in today’s rapidly evolving obesity/metabolic market,” the analysts said.
Despite these realities, Boehringer and Zealand could find a sweet spot in survodutide’s benefits on fat mass specifically. In SYNCHRONIZE-1, patients taking the GIP/GLP-1 agonist lost 34% of their visceral fat mass versus baseline, accounting for most of their overall weight reduction. Liver fat dropped 63.1% at 76 weeks. BMO analysts called the results “impressive.”
In SYNCHRONIZE-2, Boehringer noted that patients given survodutide showed significant reductions in waist circumference compared to placebo, a measure the drugmaker described as “a clinical marker closely linked to visceral fat and cardiometabolic risk.”
