Frank Vinluan , 2025-04-14 16:38:00
Pfizer is playing catch-up in the crowded field of obesity medicines, but it hoped to compete with a daily pill alternative to currently available injectable GLP-1 products. Instead, Pfizer is stopping development of its drug, danuglipron, after a liver complication emerged in a clinical trial.
The pharmaceutical giant was evaluating danuglipron in two Phase 1 dose-optimization studies. The company said Monday a patient in one of those studies experienced a potential drug-induced liver injury. This complication resolved after discontinuation of the study drug.
Novo Nordisk, with its GLP-1 agonist Wegovy, and Eli Lilly, whose drug Zepbound activates the GLP-1 and GIP receptors, currently dominate the obesity drug market. But both products are administered as once-weekly injections. Pfizer is part of a growing group of rivals aiming to differentiate from the market leaders with drugs formulated as daily pills.
Danuglipron, which was discovered internally within Pfizer, is an oral small molecule designed to bind to and activate the GLP-1 receptor. The drug was initially developed for twice-daily dosing, and mid-stage results in 2023 showed statistically significant weight loss. But many study participants also stopped taking the drug, leading Pfizer to abandon plans to advance this formulation to Phase 3 testing. Pfizer turned its focus to developing a once-daily version of danuglipron.
High levels of liver enzymes are a potential sign of liver toxicity. Pfizer said that across more than 1,400 danuglipron study participants, the overall frequency of elevated liver enzymes is in line with the approved GLP-1 drugs. But to be competitive in obesity, a drug needs to at least match the safety profile of the currently available medications, and any sign of liver injury is a red flag. Late last year, high levels of liver enzymes obeserved in Phase 2 led BioAge Labs to discontinue development of obesity drug candidate azelaprag, which it was testing in combination with Lilly’s Zepbound. Pfizer said it decided to discontinue development of danuglipron after reviewing all clinical data generated to date for the drug along with recent input from regulators.
Liver enzymes previously torpedoed another Pfizer oral GLP-1 drug. The pharma giant discontinued development of lotiglipron in 2023 due to elevated liver enzymes observed in Phase 1 testing. That’s when the company shifted focus to danuglipron. Pfizer said more detailed data from danuglipron’s clinical development program will be presented at a future scientific meeting or submitted for publication in a peer-reviewed journal.
Pfizer still has other obesity prospects in its pipeline. PF-07976016, an oral drug designed to activate the GIP receptor, is currently in Phase 2 testing. The Pfizer pipeline lists another GLP-1 agonist, PF-0695-4522, which is in Phase 1 testing for type 2 diabetes. But some analysts say the danuglipron setback may lead Pfizer to look externally for its next metabolic medicine. William Blair analyst Andy Hsieh points to Viking Therapeutics’ VK2735, an agonist of both the GLP-1 and GIP receptors, as a prospect.
A Phase 3 test of subcutaneously injected VK2735 is on track to begin Phase 3 testing in the current quarter. A Phase 2 test of an oral version of the Viking drug is ongoing with data expected in the third quarter of this year. In a research note, Hsieh said the Viking drug “could offer Pfizer a rare opportunity to reestablish not only a mere presence in obesity, but also a leading position” beyond the Novo Nordisk and Lilly drugs.
Leerink Partners Thomas Smith pointed to VK2735’s strong Phase 1b data presented during the Obesity Week conference last November. The reduction in body weight and low rates of gastrointestinal side effects compares favorably to competitors and reinforces the drug’s best-in-class potential, Smith said in a note sent to investors.
“Overall, we believe the discontinuation of danuglipron further emphasizes the importance of efficacy and safety in the competitive development landscape for obesity, and note the compelling clinical profile to date of both [subcutaneous] and oral VK2735,” he said.
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