Pfizer Selects Once-daily Modified-release Formulation for Danuglipron Following Analysis of Ongoing Clinical Trial
Once-daily formulations of the oral GLP-1 receptor agonist resulted in encouraging pharmacokinetic data for several candidates, including one showing the most favorable profile.
Pfizer announced it has selected its preferred once-daily modified release formulation for danuglipron, an oral glucagon-like peptide-1 (GLP-1) receptor agonist. The decision to proceed with a once-daily formulation is based on results from Pfizer’s ongoing pharmacokinetic study of danuglipron. To date, results have demonstrated a profile supportive of once-daily dosing.1
The open-label, randomized study (NCT06153758) is evaluating the pharmacokinetics and safety of immediate- and modified release formulations of danuglipron administered orally in healthy adults 18 years or older. In addition to data supporting a once-daily dosing, results show a safety profile consistent with prior danuglipron studies including no liver enzyme elevations observed in more than 1,400 study participants.
Looking ahead, 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.
“Obesity is a key therapeutic area for Pfizer, and the company has a robust pipeline of three clinical and several pre-clinical candidates. The most advanced of them, danuglipron, has demonstrated good efficacy in a twice-daily formulation, and we believe a once-daily formulation has the potential to have a competitive profile in the oral GLP-1 space,” Mikael Dolsten, MD, PhD, chief scientific officer & president, Pfizer Research and Development said in a press release. “Following a thorough analysis of our previous Phase IIb data and trial design, we believe that with the preferred modified release formulation and future trial design optimization, we can advance a competitive oral GLP-1 molecule into registration enabling studies, with the goal of addressing the present and persistent medical needs of people living with obesity.”
In December 2023, Pfizer shared topline Phase IIb results of danuglipron in adults with obesity. The study met its primary endpoint, demonstrating statistically significant change in body weight from baseline.2
The Phase IIb clinical trial (NCT04707313) was a randomized, double-blind, placebo-controlled, parallel group, dose-ranging study. It had 3 cohorts, with participation for the first and second being about 9 months and the third being about 10 months.3
According to Pfizer, twice-daily dosing of danuglipron showed reductions from baseline in body weight for all doses, with mean reductions ranging from -6.9% to -11.7%, compared to +1.4% for placebo at 32 weeks, and -4.8% to -9.4%, compared to +0.17% for placebo at 26 weeks. Placebo-adjusted reductions in mean body weight ranged from -8% to -13% at 32 weeks and -5% to -9.5% at 26 weeks. Depending on titration schedule, participants were at target dose levels for 6 to 24 weeks.
In an earlier press release, Dolsten said: “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. Results from ongoing and future studies of the once-daily danuglipron modified release formulation will inform a potential path forward with an aim to improve the tolerability profile and optimize both study design and execution.”
References
1. Pfizer Advances Development of Once-Daily Formulation of Oral GLP-1 Receptor Agonist Danuglipron. News release. Pfizer. July 11, 2024. Accessed July 11, 2024. https://www.businesswire.com/news/home/20240710971928/en/Pfizer-Advances-Development-of-Once-Daily-Formulation-of-Oral-GLP-1-Receptor-Agonist-Danuglipron
2. Pfizer Announces Topline Phase 2b Results of Oral GLP-1R Agonist, Danuglipron, in Adults with Obesity. News release. Pfizer. December 1, 2023. Accessed July 11, 2024. https://www.businesswire.com/news/home/20231130108413/en/Pfizer-Announces-Topline-Phase-2b-Results-of-Oral-GLP-1R-Agonist-Danuglipron-in-Adults-with-Obesity
3. A Study to Evaluate the Efficacy and Safety of PF-06882961 in Adults With Obesity. ClinicalTrials.gov. Accessed July 11, 2024. https://clinicaltrials.gov/study/NCT04707313
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