Zealand Pharma’s Roche-partnered amylin analog demonstrated “placebo-like tolerability” and up to 10.7% mean weight loss at 42 weeks in a phase 2 obesity trial.
The candidate, called petrelintide, was assessed against placebo among 493 participants who are overweight or with obesity.
The study scored on its primary endpoint, demonstrating that once-weekly injections of petrelintide resulted in statistically significant reductions in weight after 28 weeks for all five treatment arms compared to placebo, according to a March 5 release. Dosing was escalated every fourth week.
In the dose-finding trial—coded Zupreme-1—the investigational treatment was added to a reduced-calorie diet and increases in physical activity.
While the Danish drug developer didn’t unveil the average weight loss on its drug at 28 weeks, Zealand did share that the reduction was sustained through Week 42, with participants achieving up to a 10.7% mean reduction at that point compared to baseline, according to the company’s efficacy estimand. The results compare to the 1.7% weight loss seen for patients on placebo, who were also put on a reduced-calorie diet and increased their physical activity during the trial period.
Significantly, female participants in the trial lost “considerably more weight” than their male counterparts did, according to Zealand.
The company didn’t disclose data tied to specific dosing levels, but reported no vomiting or discontinuations related to gastrointestinal adverse events (AEs) at the “maximally effective dose.”
The amylin analog was tied to a 4.8% discontinuation rate due to adverse events, compared to 4.9% for patients on placebo. Gastrointestinal AEs were the most frequently reported side effects, most of which were mild, according to the company.
Across all experimental treatment arms, the proportion of participants who experienced vomiting was lower than for those on placebo. No unexpected safety signals—such as alopecia, fatigue, headache and depression—were associated with petrelintide.
The safety profile aligns with Zealand’s pitch for petrelintide to serve as a potential option for patients who cannot tolerate GLP-1 meds and want an alternative treatment for maintaining weight loss.
Zealand plans to share more of the trial results, including data from a nine-week safety follow-up period, at an upcoming scientific conference sometime this year.
“Petrelintide has the potential to redefine weight management,” Zealand CEO Adam Steensberg, M.D., said in a statement.
“Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard,” the CEO added.
Almost one year ago, Roche paid out $1.65 billion upfront and offered Zealand the chance to bank up to $3.6 billion in milestones for rights to codevelop and co-commercialize petrelintide.
Now, the partners are planning phase 3 trial designs based around the Zupreme-1 study. Roche and Zealand are also expecting top-line results from a second midstage trial—dubbed Zupreme-2—assessing petrelintide in people who are overweight or have obesity and Type 2 diabetes in the second half of this year.
Another phase 2 trial is also slated to launch this year evaluating a combination of petrelintide and CT-388, which is an investigational dual GLP-1/GIP receptor agonist from Roche’s Genentech.
Investors were less than impressed with the new data drop, with analysts at William Blair writing in a March 6 note that petrelintide's role in obesity could be “limited.”
“...[W]e believe Zealand achieved the goal of demonstrating highly encouraging tolerability for petrelintide, though the magnitude of weight loss disappointed,” the analysts wrote. “Therefore, we believe the real-world use-case for petrelintide will likely be materially reduced given the hypercompetitive nature of the obesity market.”
The data prompted William Blair to downgrade Zealand to “market perform” status and remove it from their “analyst conviction list.”
Investors agreed, sending Zealand’s stock tumbling more than 30%, falling from $369.20 per share at market close yesterday to $240.10 at 9:15 a.m. ET today.
Editor's note: This article was updated at 9:15 a.m. ET to include analyst commentary and stock information.