Boehringer's new data drop shows 19% weight loss for phase 2 obesity prospect

After teasing a small data slice in May, Boehringer Ingelheim is now sharing more on its Zealand Pharma-partnered obesity prospect, with new data showing nearly 19% weight loss in a phase 2 trial.

Last month, Boehringer revealed that recipients of survodutide, also dubbed BI 456906, lost up to 14.9% of their weight after 46 weeks, but provided little other data. Now, the pharma has unveiled additional data on the GLP-1/glucagon receptor dual agonist at the American Diabetes Association’s 83rd Scientific Sessions.

“We’re very excited by this data,” said Waheed Jamal, M.D., Boehringer Ingelheim’s corporate vice president and head of cardiometabolic medicine.

The phase 2 study enrolled 373 people who were overweight or obese without Type 2 diabetes and randomized the participants into five groups. One group received placebo treatment, while other groups experienced 20 weeks of dose escalation and 26 weeks of maintenance at doses of 0.6 mg, 2.4 mg, 3.6 mg and 4.8 mg.

“The whole purpose of the phase 2 is it’s a learning phase,” Jamal said. “You're trying to understand the best doses to take.”  

The study included two analyses: a planned analysis assessing patients by their assigned dose at randomization—regardless of whether they dosed down—and an actual analysis assessing participants by their dose group at the end of treatment, Jamal explained.

The May data were from the planned treatment analysis and demonstrated nearly 15% weight loss for all those randomized to the 4.8-mg dose group, versus 2.8% for the placebo group. Weight loss hadn’t yet plateaued at Week 46 for treated participants, suggesting additional weight loss could be achieved with a longer regimen, according to Boehringer Ingelheim.

The fresh data are from the actual treatment analysis and found that the 55 participants who completed the study on the 4.8-mg dose experienced nearly 19% weight loss, a statistically significant result that hit the study’s main goal. This is compared to just over 2% weight loss for those on placebo.

New data also zoomed in on a responder group, finding up to 40% of people who reached the highest two doses of survodutide (3.6 mg and 4.8 mg) experienced at least 20% weight loss when compared to placebo after 46 weeks.

The pharmas also provided safety data this time around, saying survodutide didn’t raise any unexpected safety or tolerability issues. A higher proportion of patients receiving placebo treatment experienced serious adverse events (6.5%) compared to participants receiving survodutide (4.2%).  

Recipients of rival GLP-1/glucagon agonists often experience gastrointestinal side effects, and survodutide appears to be no exception. Treatment discontinuation due to adverse events occurred in 24.6% of treated participants (compared to 3.9% of placebo-receiving participants), mainly due to gastrointestinal adverse events, which was expected, according to Jamal.

Most of the discontinuations due to adverse events occurred during the rapid dose-escalation phase and could be mitigated with more gradual dose escalation.  

“What we'll take forward into the phase 3 is that we will have a much lower titration—probably somewhere around every four weeks as opposed to every two weeks that we've had in phase 2,” he said. “We will allow plenty of flexible titration throughout the trial in phase 3.”

Boehringer is now in discussions with regulators about launching a phase 3 trial, Jamal said, though he didn’t reveal an anticipated timeline.

It’s predicted that half of all Americans will be obese by 2030, Jamal said, citing the timeliness of the new potential drug. While there are already several drugs used for weight loss on the market—Novo Nordisk has made the early running in the obesity market with Ozempic and Wegovy, and Eli Lilly has reported deep declines in the weight of recipients on Mounjaro—survodutide differentiates itself by acting directly on the liver. The GLP-1/glucagon agonist currently holds the potential to become the first anti-obesity med to reduce appetite while increasing energy expenditure through the liver.  

Survodutide was co-invented by Boehringer and Zealand and is part of Boehringer’s portfolio. The asset is also being assessed in phase 2 studies for nonalcoholic steatohepatitis (NASH) and liver fibrosis, and has snagged FDA fast-track designation for adults with NASH.