Clinical studies

Pfizer, stop development of oral pill for obesity after adverse event

An adverse liver event and limitations in efficacy led the company to terminate the project. Now focusing on new therapies and possible acquisitions

by Francesca Cerati

14 April 2025

2' min read

Key points

What are the alternatives?
Eli Lilly in the front row

2' min read

Pfizer decided to discontinue development of the obesity pill danuglipron after a patient suffered liver damage suspected to be related to the drug. The event, which occurred during a phase of rapid dose escalation, resolved quickly, but prompted the pharmaceutical giant to conduct a comprehensive review of the programme.

Danuglipron, a Glp-1 agonist, had undergone a series of Phase 1 clinical trials in overweight or obese patients. Despite initial positive results on pharmacokinetics and tolerability, Pfizer concluded that there was no optimal dose that could guarantee competitive efficacy and safety. The decision also came on the basis of recent input from regulatory authorities.

The pharmaceutical company had already shelved a twice-daily formulation due to gastrointestinal side effects found in Phase 2. The hope of obtaining a more tolerable version with a single daily administration is therefore definitively dashed.

What are the alternatives?

Despite the step back on danuglipron, Pfizer continues to invest in obesity. The candidate PF-07976016, an oral Gip receptor antagonist, is currently in Phase 2a. The study compares three dosages with placebo and focuses on the change in body weight after four months of treatment. Data are expected between late 2025 and early 2026.

Other companies, such as Helicore Biopharma and Antag Therapeutics, are also exploring Gip antagonism as a therapeutic strategy. 'We have a promising pipeline with oral candidates that could be combined to maximise weight loss,' said a Pfizer spokesperson.

The closure of the danuglipron programme is a disappointment for investors, and Pfizer may now look for new opportunities in the obesity sector. One possible option is Viking Therapeutics, which is about to start Phase 3 of its subcutaneous form of the drug VK2735. Preliminary data on the oral version are expected during 2025. However, with a capitalisation of around USD 2 billion, an acquisition could prove costly.

Alternatively, Pfizer could follow the example of AstraZeneca and Merck by looking to the Chinese market for acquisitions or licensing agreements.

Eli Lilly in the front row

With the failure of danuglipron, attention now turns to Eli Lilly's orforglipron, another oral Glp-1 agonist. Phase 3 data in diabetes are imminent and analysts expect a blood glucose reduction of around 2% and a weight loss of 7%.

The real test, however, will be in Phase 3 studies in obesity, with trials called Attain-1 and Attain-2, the results of which are expected in the second half of 2025. The aim is to replicate or exceed the 15% weight loss observed with Novo Nordisk's oral semaglutide, which has already been approved for diabetes, and which is also aiming for approval for the treatment of obesity this year.