Pfizer advances once-daily obesity drug to pivotal trials after setbacks

Pfizer has revitalized its oral GLP-1 candidate, danuglipron, after previously discontinuing a different version of the drug. The pharmaceutical giant has now shifted focus to a once-daily, modified-release formulation, driven by promising pharmacokinetic data.

In December 2023, Pfizer halted development of the twice-daily formulation of danuglipron due to high discontinuation rates, exceeding 50% across all studied doses. This setback compounded the difficulties in Pfizer’s obesity program, which had already suffered a blow when another once-daily candidate, lotiglipron, was discontinued due to liver dysfunction concerns.

Despite the discontinuation of the twice-daily danuglipron, Pfizer continued a pharmacokinetic study on the once-daily version. A once-daily formulation is seen as a crucial competitive edge against other major players like AstraZeneca, Eli Lilly, Structure Therapeutics, and Viking Therapeutics.

On Thursday, Pfizer provided an overview of the findings from the once-daily trial. The study revealed encouraging pharmacokinetic data for several candidates, with one exhibiting the most favorable profile. Importantly, the safety profile was consistent with previous danuglipron studies, and no patients showed elevated liver enzymes.

Pfizer’s chief scientific officer, Mikael Dolsten, M.D., Ph.D., speaking to investors in October 2023, expressed optimism about the prospect of initiating pivotal studies with a once-daily molecule in the near future. However, the pharmacokinetic data indicates that Pfizer must undertake additional work before commencing pivotal clinical trials.

The company plans to conduct dose-optimization studies, focusing on the preferred formulation to guide registration-enabling studies. These optimization studies will evaluate multiple doses throughout the second half of 2024.

The competition in this field is intense, with every month potentially making a significant difference. At an investor event in June, Pfizer CEO Albert Bourla, Ph.D., noted that danuglipron was two years behind Eli Lilly’s oral candidate but two years ahead of AstraZeneca’s program. Although Bourla did not include biotechs in his analysis, he acknowledged that Pfizer is monitoring all competitors in this space.

Pfizer has two other oral weight loss candidates with undisclosed mechanisms of action, but danuglipron remains its primary effort to launch an oral GLP-1 drug. If the once-daily version of danuglipron had failed, Pfizer might have considered mergers and acquisitions to stay competitive in the oral GLP-1 market.

Shares in Pfizer saw an increase of nearly 3%, rising above $29 in premarket trading, while shares in Viking Therapeutics fell more than 4% to $55.50.