Pfizer has axed its oral GLP-1 asset danuglipron after one patient had potential drug-induced liver injury in a phase 1 trial. The setback blows a hole in the Big Pharma’s plans to challenge for the obesity market.
The company tested once-daily danuglipron formulations in a pair of phase 1 dose-optimization studies. Pfizer said the studies met key pharmacokinetic objectives and confirmed a formulation and dose that could deliver competitive efficacy and tolerability in phase 3. Yet, the trials also brought work on the GLP-1 receptor agonist to an end.
Pfizer pulled the plug after seeing potential drug-induced liver injury in one patient. The injury resolved after the patient stopped taking danuglipron. Pfizer said the overall frequency of liver enzyme elevations across the more than 1,400 patients in the safety database was in line with approved agents in the class.
Even so, Pfizer’s review of its clinical data and input from regulators persuaded it to ax the asset. The level of competition for the oral GLP-1 space means that, if rivals avoid the liver toxicity pitfall that Pfizer fell into, patients and physicians could have treatments with a cleaner safety profile to choose from.
Pfizer scrapped another oral GLP-1 candidate, lotiglipron, in 2023 after seeing elevated liver enzymes in its clinical trials. The Big Pharma ended development of a twice-daily version of danuglipron later that year but kept going with a once-daily formulation, which could have posed a bigger threat to rivals such as AstraZeneca, Eli Lilly, Novo Nordisk, Structure Therapeutics and Viking Therapeutics.
The discontinuation of danuglipron takes out the centerpiece of Pfizer’s push into obesity and raises the question of whether the company will strike a deal to reclaim a place in the race. Shares in Structure and Viking rose 10% and 13%, respectively, in premarket trading Monday.
Pfizer has an oral small molecule GIPR antagonist in phase 2 development in adults with obesity. Talking to investors on an earnings call in February, Pfizer Chief Scientific Officer Chris Boshoff, M.D., Ph.D., said the molecule could form part of a fixed-dose combination with danuglipron. The discontinuation takes the prospect of a GIPR-GLP-1 combination off the table for now.