Zealand Pharma has reported more phase 2 data on its Roche-partnered amylin analog, linking the drug candidate to competitive weight loss but a lackluster effect on blood sugar.
The data come from Zupreme-2, a midphase trial that enrolled 220 people with overweight or obesity and Type 2 diabetes. Each week, participants received placebo or one of three doses of petrelintide, the drug candidate that Roche picked up for $1.65 billion plus milestones last year. Zupreme-1, a phase 2 trial that excluded people with Type 2 diabetes, raised doubts about petrelintide’s competitiveness.
Doubts remain following the release of topline data from Zupreme-2. Zealand reported mean weight loss on petrelintide of up to 9.2% at Week 28, compared to 2% for placebo. While weight loss is typically lower in people with Type 2 diabetes, Zealand came close to replicating the 9.8% result from Zupreme-1.
In a note to investors, William Blair analysts called the Zupreme-2 weight-loss data “intriguing.” As the analysts pointed out, the 7.2% placebo-adjusted result matched the weight loss Eli Lilly reported in a phase 2 trial of its amylin receptor agonist, eloralintide. Novo’s CagriSema drove deeper weight loss in phase 3, but it targets amylin and GLP-1.
Cross-trial blood sugar comparisons were less favorable for petrelintide. At 0.65%, the Week 28 decline in HbA1c on the drug candidate fell short of the bar set by rivals, which ranges from 1.3% to 2.1%. The gap between petrelintide and the competition is smaller after adjusting for placebo because HbA1c rose in the control arm. A rise in HbA1c is “unusual” in such studies, the analysts said.
Tolerability, a key part of Zealand and Roche’s petrelintide pitch, impressed again. Petrelintide’s profile was “largely comparable” to placebo, Zealand said. In the petrelintide arms, 1.9% of people discontinued treatment because of gastrointestinal adverse events, compared to 1.7% of patients on placebo.
After the readout, William Blair analysts said they “continue to believe petrelintide offers patients an improved treatment experience due to its differentiated tolerability profile.” However, assessing data from across the two phase 2 trials, the analysts said weight loss disappointed, as did HbA1c in Zupreme-2.
“Our current view is that petrelintide will likely be used primarily in the maintenance setting, which demands a therapeutic intervention that exhibits placebo-like tolerability for chronic use,” the analysts said. “There will also likely be clinical utility in the overweight segment ... as a double-digit weight loss in that setting could lead to normal weight and improved cardiovascular risk.”
Roche recently began enrolling participants in a trio of phase 3 trials of petrelintide. The pivotal program includes Zupreme-4, which is recruiting 600 people with overweight or obesity and Type 2 diabetes.
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