Pfizer's beleaguered obesity strategy has hit another setback as the pharma jettisoned its third and final GLP-1 agonist, citing poor data and tough competition.
Pfizer's last remaining GLP-1 agonist, dubbed PF-06954522, grew out of the company’s work with Sosei Heptares and entered a phase 1 study back in 2023. Discussing the asset later that year, Pfizer’s chief scientific officer at the time, Mikael Dolsten, told analysts that the company was “building a platform” around GLP-1 and had “a pretty strong effort here.”
But Pfizer's obesity strategy soon ran into some liver-related problems. By the end of 2023, Pfizer had already scrapped an oral GLP-1 candidate called lotiglipron after seeing elevated liver enzymes in its clinical trials. Four months ago, the company abandoned another oral GLP-1 drug called danuglipron after one patient had potential drug-induced liver injury in a phase 1 trial.
Now, PF-06954522 has also been discontinued, Pfizer confirmed to Fierce Biotech this morning. When asked whether PF-06954522 encountered similar liver problems to those seen with lotiglipron or danuglipron, a spokesperson told Fierce that the decision to end development “was not related to any safety concerns that arose in the phase 1 program.”
Instead, Pfizer made the call “following a review of data from its phase 1 program and the GLP-1 landscape.”
“We continue to apply our global capabilities to advance a pipeline of investigational treatments that have the potential to fill critical gaps in patient care for cardiovascular and metabolic diseases, including obesity,” the spokesperson said.
It leaves Pfizer’s hollowed-out obesity strategy now reduced to PF-07976016, a GIPR antagonist in phase 2 development. Talking to investors on an earnings call in February, Pfizer's current chief scientific officer Chris Boshoff, M.D., Ph.D., suggested the molecule could form part of a fixed-dose combination with danuglipron—but that door has now closed.
In a sign that Pfizer's in-house setbacks mean the company may have to look elsewhere to regain a competitive position in the fast-moving obesity race, the spokesperson added that the pharma will “also continue to evaluate external opportunities to complement our internally discovered and developed molecules.”
In the company's second-quarter earnings call today, CEO Albert Bourla, Ph.D., explained that obesity and cardiometabolic disease remains an active area for Pfizer, alongside oncology, vaccines and internal medicine. When it comes to building the pharma's pipeline in these areas, the focus will be on multiple small transactions, Bourla said, rather than one big deal.
And Pfizer's M&A efforts in obesity “will be very disciplined,” he added. “We will not overpay. We will pay the real value that the asset deserves.”
The story is more positive for PF-06425090, Pfizer’s C. difficile vaccine that has also been discontinued, according to the company’s pipeline update.
Back in 2022, Pfizer reported that the vaccine had missed the primary endpoint of stopping primary C. difficile infection (CDI) in a late-stage study of 17,500 adults aged 50 years and older. At the time, the Big Pharma wasn’t ready to give up, pointing to zero cases of medically attended CDI in the PF-06425090 arm compared to 11 cases in the placebo cohort.
It looks like Pfizer’s hard work on PF-06425090—a vaccine composed of genetically modified toxins A and B from C. difficile—won’t have been in vain. The pharma used its earnings presentation to highlight to investors that it has been working on a new formulation of the vaccine to produce a next-gen candidate that it hopes to take into phase 3 later this year.
A phase 2 trial has already shown that this updated vaccine resulted in a four-fold increase in functional toxin-neutralizing antibody titers compared to PF-06425090, according to this morning’s presentation slides.
Unlike its ancestor, the new vaccine will only require two doses instead of three, Pfizer said. It also contains an adjuvant to “increase the strength and magnitude of the immune response.”
With around 500,000 CDIs in the U.S. a year and 30,000 deaths, according to U.S. Centers for Disease Control and Prevention data cited by Pfizer, it’s easy to see why the company isn’t willing to give up on its ambition of getting the first vaccine for primary or recurrent C. difficile infection to market.
Joining the GLP-1 drug and the vaccine on the scrapheap this morning were two phase 1 assets. One of these was PF 07293893, an AMP-activated protein kinase activator that was being developed for heart failure. There was also PF-07820435, an oral STING agonist for solid tumors that Pfizer confirmed had been discontinued.
Editor's note: This story was updated at 12 p.m. ET to add information from Pfizer's second quarter earnings call.
Darren Incorvaia contributed to this report.