Pfizer advances development of once-daily formulation of oral GLP-1 receptor agonist danuglipron.

Pfizer plans to conduct dose optimization studies in the second half of 2024 evaluating multiple doses of the preferred modified release formulation to inform the registration enabling studies.

The ongoing open-label, randomized study is evaluating the pharmacokinetics and safety of immediate- and modified release formulations of danuglipron administered orally in healthy adults 18 years or older. To date, study results have demonstrated a pharmacokinetic profile supportive of once-daily dosing with a safety profile consistent with prior danuglipron studies including no liver enzyme elevations observed in more than 1,400 study participants.

Comment: In recent clinical trials, danuglipron has shown promising results. A Phase IIb study demonstrated statistically significant weight loss in adults with obesity. Participants experienced mean placebo-adjusted weight reductions ranging from -8% to -13% at 32 weeks and -5% to -9.5% at 26 weeks. However, the trials also reported high discontinuation rates, with more than 50% of participants dropping out, largely due to gastrointestinal side effects such as nausea, vomiting, and diarrhea. Despite these challenges, Pfizer is optimistic about the potential of danuglipron. The company has decided to focus on developing a once-daily modified-release formulation, aiming to improve the drug's tolerability and efficacy. This decision follows the discontinuation of the twice-daily version of danuglipron due to its lower tolerability. Pfizer plans to continue clinical studies on the once-daily formulation, with further pharmacokinetic data expected in the first half of 2024.