Roche-Zealand Obesity Drug Petrelintide Shows 10.7% Weight Loss in Phase 2 Trial
Zealand Pharma's petrelintide achieved up to 10.7% average weight loss after 42 weeks in a 493-patient phase 2 trial, with placebo-like tolerability but lower efficacy than competing amylin drugs, causing Zealand shares to drop 34%.
Shares in Zealand Pharma lost around a third of their value today, after it reported phase 2 data with Roche-partnered weight-loss therapy petrelintide. The once-weekly, injectable amylin analogue achieved up to a 10.7% average reduction in body weight after 42 weeks in the trial, compared to a 1.7% drop with placebo.
The disappointment likely stems from comparisons with Eli Lilly's rival amylin-targeting drug, eloralintide, which achieved average weight loss of up to 20% in a mid-stage trial reported last November.
Roche said it was pleased with the results of the 493-patient ZUPREME-1 trial, however, pointing out that the efficacy results back the potential of petrelintide on its own for chronic weight management, while the "placebo-like tolerability" means it could be added to combination therapies using other drugs, like GLP-1 agonists.
There were no cases of vomiting and no treatment discontinuations due to gastrointestinal adverse events, the main side effect seen with GLP-1 drugs, even at the highest dose tested in the study, according to the companies. Trial withdrawal due to side effects was 4.8% at the top petrelintide dose, compared to 4.9% with placebo.
In the eloralintide trial, around a third of patients experienced nausea at the top dose, with 43% reporting fatigue, and 10% discontinued treatment.
The tolerability profile has been one of the key drivers for its development, and the efficacy result is a little better than was seen in earlier clinical trials. One interesting finding was that female participants lost considerably more weight than male participants in the study, which enrolled overweight or obese patients with associated conditions like high blood pressure and high cholesterol.
Denmark-based Zealand bore the brunt of investor jitters, with shares sliding more than 34%, while Roche also weakened with a 2.3% decline.
"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," commented Roche's chief medical officer. "[This] data reinforce[s] our confidence in petrelintide's potential to address important unmet medical needs in chronic weight management."
Roche licensed petrelintide from Zealand last year for a hefty $1.4 billion upfront payment, adding it to a portfolio of half a dozen clinical-stage candidates, including dual GIP/GLP-1 agonist CT-388, which achieved weight loss of up to 22.5% in a phase 2 study reported in January.
The readout leaves Roche and Zealand waiting for the results of ZUPREME-2, in people who are overweight or obese and also have type 2 diabetes, which are due in the latter half of 2026. The companies also plan to start a combination trial of petrelintide and CT-388 before the end of this year.
"Petrelintide has the potential to redefine weight management," said Zealand's chief executive. "Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard."