Pfizer has terminated one of its glucagon-like peptide-1 receptor agonist (GLP-1-RA) candidates as the race heats up to market the first oral weight loss drug.

The loss of lotiglipron means Pfizer will rest its hopes on its other candidate danuglipron to take on Novo Nordisk and Eli Lilly for the first marketed weight loss pill. The market responded accordingly to Pfizer’s announcement about shelving the program, with shares in the company opening 3% lower on Monday morning compared to pre-announcement market close (23 June).

The decision to scrap lotiglipron was due to elevated levels of transaminases seen in two Phase I studies and a currently ongoing Phase II study. Pfizer said no liver-related symptoms or side effects were observed and added that the increase in transaminase levels has not been seen in any of its danuglipron trials.

Pfizer has already published results for danuglipron in the Journal of the American Medical Association Network Open. In a Phase II study (NCT03985293), danuglipron significantly reduced HbA1c and fasting plasma glucose (FPG) in patients with type 2 diabetes. Pfizer is also currently undertaking a Phase II study for the drug in non-diabetic patients with obesity, which it expects to complete by the end of the year. By then, Pfizer also says it will also have drawn up final plans for the rest of the danuglipron late-stage programme.

Pfizer is going head-to-head against Novo Nordisk – a formidable force in the weight loss therapy market. At the American Diabetes Assocation annual meeting, Novo Nordisk announced positive results – demonstrating a 15% in weight loss – from a high-dose oral version of its highly popular drug semaglutide, marketed as Ozempic (for treating type 2 diabetes) and Wegovy (for treating obesity). The popularity of the drug, which is currently administered via an injection, has meant the company recently limited starter doses in an effort to fix supply shortages.

Pfizer’s decision to scrap one of its candidates comes amidst news from Eli Lilly showing promising early results with its weight loss pill orforglipron. In a Phase II study, the drug led to a 15% weight loss, in line with Novo Nordisk’s recent results for its pill.

Eli Lilly is riding a wave of success after trial completions for its type 2 diabetes drug Mounjaro (tirzepatide). In a reflection of its current positive sentiment, Eli Lilly recently splashed out $2.4bn to shore up its immunology offering.

“If successful in clinical trials and approved, danuglipron could be in a prime position to differentiate based on profile, including full receptor agonism, which we believe has the potential to translate to robust efficacy,” said William Sessa, PhD, Pfizer’s senior vice president and chief scientific officer in a statement announcing the company’s strategic plans.

Reference: https://www.pharmaceutical-technology.com/news/pfizer-shelves-one-oral-pill-pivots-to-another-in-weight-loss-drug-race/