Roche, Zealand tout the tolerability of their amylin obesity drug

Roche's experimental amylin shot, petrelintide, acquired nearly a year ago as part of a $1.65 billion deal with Zealand Pharma, showed a differentiated "placebo-like tolerability" profile in a mid-stage obesity trial, the companies reported on Thursday.

In the Zupreme-1 study, which enrolled nearly 500 patients with a mean BMI of 37, petrelintide helped participants lose up to 10.7% of their mean body weight, compared with 1.7% among those who took a placebo. Although dosing details were not disclosed, weight loss continued through week 42, Roche said in its press release.

Roche and Zealand's amylin analogue was also well tolerated, with a side effect profile consistent with that of the placebo arm of the study.

"Petrelintide has the potential to redefine weight management," Zealand's President and Chief Executive Officer, Adam Steensberg, said. "Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard."

Petrelintide had a 4.8% discontinuation rate due to adverse events, which was slightly lower than the 4.9% observed in the placebo arm. Gastrointestinal (GI) events were the most frequently reported side effects, and most were mild, the two companies said.

More notably, petrelintide performed better than the placebo regarding the side effects commonly associated with popular GLP-1 drugs.

Despite the proven therapeutic benefits of GLP-1 drugs, real-world discontinuation rates remain high, partly due to gastrointestinal side effects such as nausea, vomiting, diarrhea, gastroparesis and pancreatitis.

In all petrelintide treatment groups, the incidence of vomiting was lower than in the placebo arm, with the highest-efficacy dose showing no cases. Diarrhea and constipation rates were also consistent with those observed in patients taking a placebo, Roche said.

Most strikingly, the overall trial withdrawal rate for any reason was 8.4% across all petrelintide groups, compared to 13.6% in the placebo arm, indicating patients on the Roche–Zealand drug were actually less likely to drop out than those not taking it.

But petrelintide's strong tolerability profile couldn't cushion the blow of the drug's single-digit placebo-adjusted weight loss percentage, which may have caused Zealand's share price to tumble more than 30% this morning. While tolerability is a meaningful differentiator in a class notorious for GI side effects, weight loss efficacy remains the primary driver in the obesity market.

Still, both companies expressed confidence in their assets' potential to offer a more tolerable weight loss solution than what is currently available on the market.

"Petrelintide achieved meaningful weight loss with a well-tolerated dosing approach, which is essential to support long-term and sustained benefits in people living with obesity," Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development said. "Therefore, these data reinforce our confidence in petrelintide's potential to address important unmet medical needs in chronic weight management."

Roche and Zealand said they are advancing petrelintide to stage 3 testing later this year. Top-line results from Zupreme-2, a second phase 2 study testing petrelintide in patients who are overweight or living with obesity or type 2 diabetes, are expected in the second half of 2026.

A separate mid-stage trial evaluating petrelintide with Roche's investigational dual GLP-1/GIP receptor agonist, which the company picked up from its $2.7 billion acquisition of Carmot Therapeutics, is also slated to begin this year.

Petrelintide is one of several amylin analogues advancing through clinical development. Industry titans including Eli Lilly, Novo Nordisk, AbbVie/Gubra, AstraZeneca and Pfizer/Metsera are all running trials on amylin analogues.

Eli Lilly's candidate, eloralintide, is currently leading the clinical pack. Patients who received the highest dose of Lilly's drug lost an average of 20.1% of their body weight after 48 weeks in a phase 2 trial, and the drug was advanced to phase 3 testing in December.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.