Pfizer's weight-loss aspirations are dealt a heavy blow
Pfizer has been forced to discontinue its oral GLP-1 receptor agonist danuglipron after seeing signs of liver toxicity in late-stage clinical testing.
The decision is a massive blow to Pfizer's ambitions in obesity as it tries to catch up with the leaders in the GLP-1 category, Novo Nordisk and Eli Lilly, whose injectable Wegovy (semaglutide) and Zepbound (tirzepatide) products are currently enjoying what is effectively a duopoly in the weight-loss market.
It's doubly disappointing for the company as it was advancing multiple candidates through earlier-stage development before deciding last year that its front runner should be danuglipron (PF-06882961), saying its once-daily dosing and tolerability profile made it a contender among a long list of clinical candidates hoping to offer an oral alternative.
Pfizer was also developing a twice-daily formulation of the drug, which showed promising weight loss, but was plagued by gastrointestinal side effects and a high discontinuation rate, as well as another candidate called lotiglipron that was shelved after the company saw a signal that it may cause liver toxicity.
That story has been repeated with once-daily danuglipron, it seems. In a statement, Pfizer said that it had seen elevations in liver enzymes – a possible marker for liver damage – in clinical trials that were "in line with approved agents in the class." However, there was one patient who had what appeared to be drug-induced liver injury, with no symptoms.
While that resolved after treatment was discontinued, Pfizer has concluded that it will discontinue the danuglipron programme after reviewing "the totality of information, including all clinical data generated to date […] and recent input from regulators."
The demise of danuglipron means that its clinical-stage obesity pipeline is now represented by PF-07976016, another oral drug that targets GLP-1 and gastric inhibitory peptide (GIPR) and is in phase 2 testing.
"We plan to continue applying our global capabilities to advance a pipeline of investigational treatments that have the potential to fill critical gaps in patient care, including continued development of our oral GIPR antagonist candidate and other earlier obesity programmes," said Chris Boshoff, Pfizer's chief scientific officer.
"While we are disappointed to discontinue the development of danuglipron, we remain committed to evaluating and advancing promising programmes in an effort to bring innovative new medicines to patients."
Companies trying to develop oral weight-loss candidates include Novo Nordisk, which has an oral formulation of semaglutide in late-stage development and another called amycretin in phase 1, and Lilly, which is testing orforglipron in phase 3. Meanwhile, other oral candidates are coming through the clinical pipeline from Roche, Amgen, AstraZeneca, and others.
