Pfizer said Monday it will halt development of its once-daily obesity pill danuglipron following a safety concern identified in early-stage testing, marking another setback in the company's push to enter the lucrative weight loss drug market dominated by rivals Eli Lilly and Novo Nordisk. The decision comes after a patient in a clinical trial experienced a potential drug-induced liver injury that resolved after the treatment was discontinued.
According to Pfizer, a participant in the danuglipron trial experienced elevated liver enzymes, which often indicate damage to cells in the liver, and the enzymes "recovered rapidly" after the patient stopped taking the drug. The case occurred in a trial that rapidly increased the dose over a short period of time.
Dr. Chris Boshoff, Pfizer's Chief Scientific Officer, stated, "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." Pfizer said the decision followed a review of total clinical data and discussions with regulators.
The development halt is the second blow to the danuglipron program. Pfizer scrapped a twice-daily version in December 2023 after more than half of patients in a mid-stage trial discontinued treatment due to tolerability issues. Despite initial confidence in the once-daily formulation, Pfizer will also discontinue testing danuglipron in combination with other drugs.
Danuglipron is part of a class of drugs known as GLP-1 receptor agonists, which mimic gut hormones to regulate appetite and blood sugar. The category has become one of the hottest areas in the pharmaceutical industry, with some analysts projecting the market could exceed $150 billion by the early 2030s. Oral versions alone may account for $50 billion of that total.
Novo Nordisk's Rybelsus, the only oral GLP-1 drug currently approved by the FDA, brought in $3.38 billion in 2024. Meanwhile, Lilly's injectable Zepbound and diabetes treatment Mounjaro, which target both GLP-1 and GIP, posted a combined $5 billion in weight loss sales last year. Both companies are advancing their own oral obesity therapies, with Lilly expected to release new trial data later this year.
Pfizer said studies of its once-daily danuglipron formulation had met certain goals and demonstrated "competitive efficacy and tolerability," but the liver signal led to the discontinuation decision. The company noted the rate of liver enzyme elevations was consistent with approved GLP-1 therapies and cited safety data from over 1,400 patients.
This is not Pfizer's first liver-related issue with oral obesity drug candidates. In June 2023, it abandoned a separate once-daily candidate after patients showed elevated liver enzymes during a mid-stage trial.
While danuglipron is now shelved, Pfizer still has early-stage candidates in development. These include a Phase 2 oral drug that targets the gut hormone GIPR and a separate GLP-1 compound in Phase 1. Former Chief Scientific Officer Mikael Dolsten said in October that targeting GIPR may offer better efficacy and tolerability, adding, "There are so many applications for GLP-1s."
The company has signaled that obesity remains a strategic priority despite recent challenges. Pfizer is also focused on expanding its oncology portfolio to support long-term growth following the decline of its Covid-19 vaccine and treatment business.
Pfizer shares rose 12 cents to $22.03 in morning trading Monday. Investors, who have grown skeptical of Pfizer's late entry into the obesity race, are watching closely for progress in its next-generation weight loss pipeline.
