Pfizer drops twice-daily obesity therapy due to side effects


Pfizer has decided to discontinue the development of another of its experimental obesity therapies, after seeing high rates of discontinuation with the drug in a mid-stage trial.

The company is axing twice-daily oral GLP-1 receptor agonist danuglipron and instead will switch to a once-daily version of the drug codenamed PF-06882961. It said patients taking the drug had seen significant weight loss ranging from 8% to 13% after 32 weeks of treatment, depending on dose, in the phase 2b trial.

“While most common adverse events were mild and gastrointestinal in nature consistent with the mechanism, high rates were observed,” said Pfizer, with discontinuation rates of more than 50% across the dose range, compared to around 40% for placebo.

The once-daily formulation of danuglipron is currently in a pharmacokinetic study, “the outcome of which will inform a path forward,” said the firm, which had been predicting the start of phase 3 testing for twice-daily danuglipron before the end of the year.

It’s the second time that Pfizer has abandoned an obesity drug this year, coming after it abandoned another once-daily GLP-1 agonist – called lotiglipron – over concerns about liver safety.

“We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile,” commented Mikael Dolsten, Pfizer’s chief scientific officer.

There’s no question, however, that the decision to abandon the twice-daily version introduces a significant delay to Pfizer’s plans to enter the obesity market, which has been transformed in the last couple of years by injectable drugs working on GLP-1, such as Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s just-approved Zepbound (tirzepatide), which also hits GIP.

Both Novo Nordisk and Lilly are working on orally active therapies to expand their obesity portfolios, with the former currently leading the charge with a phase 3 readout for its oral semaglutide for obesity due in the first quarter of 2024. The drug is already approved as Rybelsus for type 2 diabetes.

Lilly, meanwhile, reported phase 2 results with its once-daily oral-GLP-1 drug orforglipron in the summer, with a near 15% weight reduction at 36 weeks in type 2 diabetics at the optimal dose, and has advanced the drug into phase 3. It also reported preliminary data with an oral triple agonist called retatrutide – targeting GLP-1, GIP, and glucagon – that is also being advanced quickly into phase 3.

Shares in Pfizer fell around 5% in the wake of the announcement.