Pfizer has dragged the oral GLP-1 candidate danuglipron back from the brink. Months after dropping one version of the asset, the Big Pharma has vowed to advance a once-daily, modified-release formulation on the strength of “encouraging pharmacokinetic data.”
The drugmaker axed twice-daily danuglipron in December 2023 after reporting discontinuation rates in excess of 50% across all the studied doses. The data dealt another blow to Pfizer’s obesity program, which was still reeling from the discontinuation of once-daily lotiglipron in response to signs of liver dysfunction.
When Pfizer dropped twice-daily danuglipron, a pharmacokinetic study of the once-daily version of the molecule kept rolling. Having a once-daily formulation would make Pfizer more competitive against rivals such as AstraZeneca, Eli Lilly, Structure Therapeutics and Viking Therapeutics.
Thursday, Pfizer shared a high-level overview of what was learned in the once-daily trial. The researchers saw “encouraging pharmacokinetic data for several candidates with one showing the most favorable profile,” Pfizer said, and “a safety profile consistent with prior danuglipron studies.” No patients had elevated liver enzymes.
Talking to investors in October 2023, Mikael Dolsten, M.D., Ph.D., chief scientific officer at Pfizer, said “it's within our reach, if we decide to start the pivotal study next year, to do it with a once-a-day molecule.”
However, the data from the pharmacokinetic study have left Pfizer with work to do before starting pivotal clinical trials. First, the company plans to conduct dose-optimization studies “with a focus on the preferred formulation to inform the registration enabling studies.” Pfizer will assess multiple doses in the optimization studies over the second half of 2024.
Every month may matter in what is shaping up to be a highly competitive space. Talking at an investor event in June, Pfizer CEO Albert Bourla, Ph.D., said (PDF) danuglipron was two years behind Lilly’s oral candidate and two years ahead of AstraZeneca’s program. Bourla’s analysis of the race excluded biotechs, but the CEO said “we are looking [at] all of them” when asked whether he was paying attention to smaller players.
Pfizer has two other oral weight loss candidates with undisclosed mechanisms of action, but danuglipron is its lead attempt to get an oral GLP-1 drug to market. If once-daily danuglipron had failed, Pfizer could have looked to M&A to regain a spot in the oral GLP-1 race. Shares in Pfizer rose almost 3% to above $29 in premarket trading. Shares in Viking fell more than 4% to $55.50.