Pfizer ends development of oral weight-loss drug

In a phase 2b trial, Pfizer enrolled around 600 adult patients who were obese but did not have Type 2 diabetes. The trial evaluated the effectiveness of twice-daily danuglipron, an experimental oral medication for weight loss.

In the trial, researchers tested the drug's effect on patients' weight loss after 26 or 32 weeks and at different dosage amounts that ranged from 40 milligrams to 200 milligrams. Patients who took the pill twice a day lost an average of 4.8% to 9.4% of their body weight at 26 weeks and 6.9% to 11.7% at 32 weeks.

Meanwhile, patients in the trial who took a placebo gained 0.17% of their body weight at 26 weeks and 1.4% at 32 weeks. After adjusting for the placebo results, danuglipron resulted in an average 5% to 9.5% weight loss at 26 weeks and 8% to 13% at 32 weeks.

Although the medication met its primary target in the trial, the weight loss observed was smaller than those reported in trials of similar medications developed by other companies. There were also high rates of adverse side effects among patients. Up to 73% of patients reported experiencing nausea, up to 47% reported vomiting, and up to 25% reported diarrhea.

In addition, over 50% of patients across all dose sizes in the medication group discontinued the medication, compared to around 40% of patients in the placebo group.

Based on these results, Pfizer said it will not move the twice-daily danuglipron into Phase 3 trials, focusing instead on a once-daily version of the drug. Currently, the once-daily version is undergoing pharmacokinetic studies, and data is expected in the first half of 2024.

According to Mikael Dolsten, Pfizer's chief scientific officer, the company believes that the once-daily version of danuglipron could be effective for treating obesity. "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," Dolsten said.

Other companies' weight-loss pills

According to STAT_­+, several other companies are also testing oral weight-loss drugs, with at least 28 other medications in development. Many of these companies are ahead of Pfizer in their efforts, reporting better weight loss results and lower discontinuation rates among trial patients.

For example, Eli Lilly is currently working on a once-daily weight-loss pill called orforglipron. In a 36-week Phase 2 trial, the pill led to 15% weight loss among patients. It is now being tested in a Phase 3 trial.

Separately, Novo Nordisk recently completed a Phase 3 trial for an oral version of semaglutide, the ingredient used in Wegovy, its injectable drug for diabetes and weight-loss. The oral version of semaglutide led to 15% weight loss over 17 months.

According to Louise Chen, an analyst at Cantor Fitzgerald, Wall Street was looking for danuglipron to result in 14% to 15% weight loss for it to be competitive against other medications currently in development.

Steve Scala, an analyst at TD Cowen, said the weight-loss pills from Eli Lilly and Novo Nordisk seem to be "superior to [Pfizer's] danuglipron at this stage." (Joseph/Chen, STAT+ [subscription required], 12/1; Murphy, Associated Press, 12/1; Constantino, CNBC, 12/1)

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