Pfizer to discontinue development oral GLP-1 receptor agonist Danuglipron

Pfizer has decided to discontinue development of danuglipron (PF-06882961), an oral glucagon-like peptide-1 (GLP-1) receptor agonist, which was being investigated for chronic weight management.

Pfizer’s dose-optimisation studies of once-daily formulations of danuglipron (NCT06567327 and NCT06568731) met key pharmacokinetic objectives and confirmed a formulation and dose with the potential to deliver a competitive efficacy and tolerability profile in Phase 3 testing, based on earlier studies of twice-daily danuglipron.

While the overall frequency of liver enzyme elevations across the over 1,400 participant safety database of danuglipron is in-line with approved agents in the class, a single asymptomatic participant in one of the dose-optimization studies experienced potential drug-induced liver injury which resolved after discontinuation of danuglipron. After a review of the totality of information, including all clinical data generated to date for danuglipron and recent input from regulators, Pfizer has decided to discontinue development of the molecule.

“Cardiovascular and metabolic diseases including obesity remain important areas of unmet medical need, and we plan to continue applying our global capabilities to advance a pipeline of investigational treatments that have the potential to fill critical gaps in patient care, including continued development of our oral GIPR antagonist candidate and other earlier obesity programs,” said Dr Chris Boshoff, Chief Scientific Officer and President, Research and Development at Pfizer. “While we are disappointed to discontinue the development of danuglipron, we remain committed to evaluating and advancing promising programs in an effort to bring innovative new medicines to patients.”

In June 2023, the company announced it was discontinuing the clinical development of another GLP-1-RA candidate, lotiglipron, after pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements showed elevated transaminases in these Phase 1 studies as well as the ongoing Phase 2 study.

In December 2023, the company announced its twice-daily danuglipron formulation would be discontinued after high rates of GI complaints. The twice-daily danuglipron formulation resulted in high rates of gastrointestinal complaints (73% nausea; 47% vomiting; 25% diarrhoea). High discontinuation rates, greater than 50%, were seen across all doses compared to approximately 40% with placebo.

Data from the danuglipron clinical development program will be presented at a scientific forum or submitted for publication in a peer-reviewed journal in the future.