Pfizer Decides Against Pursuing Lead Obesity Asset Amid Liver Safety Concerns

Pfizer said that it had discovered a possible instance of medication-induced liver impairment and, as a result, would no longer be investing in the manufacturing of its oral GLP-1 medicine danuglipron.

According to a note from BMO Capital Markets, Pfizer is starting all over, even though danuglipron isn’t the only asset that it holds in relation to obesity.

As per Pfizer, the patient who had liver damage during the dose-optimization trials had no symptoms, and the side effect went away after they stopped using danuglipron. According to the pharmaceutical company, the total incidence of liver enzyme increases in over 1,400 individuals treated so far is comparable to other authorized medicines in this class.

Having said that, after reviewing the material – including all of the clinical data gathered so far – and discussing it with the regulators, Pfizer still decided to part ways with danuglipron.

Now that danuglipron is no longer being developed, Pfizer only has the oral GIP analog PF-07976016, which is in the second phase of clinical trials for obesity, to rely on. The research is scheduled to initially conclude in December 2025, as reported in a federal clinical trials registry.

Danuglipron, like other medications in its class, such as Wegovy and Zepbound, supports the body’s reaction to blood sugar increases by increasing insulin production by targeting and stimulating the GLP-1 receptor. Danuglipron helps reduce hunger and appetite by reducing gastric emptying as well.

In spite of its well-defined system of action, danuglipron has had difficulties in demonstrating its clinical efficacy. In December 2023, Pfizer issued the halting of danuglipron testing as a bi-daily tablet after the observation of elevated adverse effect rates in a Phase IIb trial. As many as 73% of treated individuals reported nausea, while around 25% and 47% had diarrhea and vomiting, respectively.

Pfizer disclosed that the rate of discontinuation due to adverse events exceeded 50% across all dosages of danuglipron.

In July 2024, the pharmaceutical company said that it had modified the formulation of danuglipron and will proceed with its development as a once-daily tablet. This action reinstated danuglipron to Phase I trials, although the setback seemed to have little impact on the firm’s dedication to weight reduction initiatives.

During the January 2025 J.P. Morgan Healthcare Conference, CEO Albert Bourla reaffirmed Pfizer’s commitment to obesity treatment and announced the recruitment of additional experts for decision-making. However, he moderated investors’ expectations regarding danuglipron, expressing considerable caution about the asset.

In a note released Monday, analysts stated, “VK2735 could offer Pfizer a rare opportunity to reestablish not only a mere presence in obesity, but also a leading position beyond” the current Novo Nordisk/Eli Lilly duopoly.”

Danuglipron is not Pfizer’s first unsuccessful weight-loss medication. In June 2023, the firm discontinued lotiglipron, another GLP-1 treatment, which it had been evaluating for obesity and type 2 diabetes. Lotiglipron was linked to liver safety concerns, including increased transaminase levels.