Pfizer has discontinued development of the investigational weight-loss agent danuglipron following a case of suspected drug-induced liver injury in a clinical trial participant, which resolved upon discontinuation of the drug.
The company had been testing multiple doses of a once-daily version of the oral drug after scrapping development of a twice-daily version in late 2023 due to a high discontinuation rate in a mid-stage trial, primarily attributed to gastrointestinal adverse events such as nausea and vomiting.
Danuglipron was being evaluated as a potentially more convenient alternative in the lucrative weight-loss drug market, currently dominated by Novo Nordisk's Wegovy and Eli Lilly's Zepbound, both of which are administered via weekly injection.
The therapeutic class has garnered significant interest from pharmaceutical companies and investors and is projected to reach $150 billion in annual sales in the coming years.
Danuglipron is a GLP-1 receptor agonist, targeting the glucagon-like peptide-1 pathway.
Several pharmaceutical companies are developing oral GLP-1 receptor agonists, including Lilly, which is expected to announce Phase 3 trial results for its agent orforglipron imminently.
Shares of Lilly climbed 2.5% in early trading, while Novo Nordisk's Copenhagen-listed shares rose over 3%.
The discontinuation of danuglipron sends Pfizer back to the starting block, BMO Capital Markets analyst Evan Seigerman said, noting that its other obesity candidates remain in early stages of clinical development. Seigerman added that Pfizer may now pursue a deal or partnership in the near term.
Shares of smaller weight-loss treatment developers such as Viking Therapeutics and Structure Therapeutics also rose between 8% and 15% on the news.
Pfizer said dose-optimization studies of once-daily danuglipron showed that the overall frequency of liver enzyme elevations across 1,400 study participants was consistent with approved agents in the class. One participant, however, developed liver injury.
“After a review of the totality of information, including all clinical data generated to date for danuglipron and recent input from regulators,” Pfizer said it has decided to discontinue studying the molecule.
The company will continue development of its investigational oral agent targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR), along with other earlier-stage obesity program candidates.
Pfizer noted that data from the danuglipron clinical program will be presented at a forthcoming scientific meeting or submitted for peer-reviewed publication.