One year ago, Pfizer CEO Albert Bourla stated that in the field of obesity, "we have the ability and the right to compete and win." A year later, Bourla reiterated at the JPM conference that Pfizer would go "all-in" on weight loss drug development, noting that the company had been recruiting experts in obesity.
Despite setbacks with two small molecule GLP-1s, Pfizer has become more determined. Currently, the company is developing danuglipron, an oral tablet to be taken once daily. The new formulation is undergoing dose optimization, and data is expected in a few months to confirm whether it can replicate the results seen in the phase 2b trial. It is also expected to begin phase 3 clinical trials in the second half of this year.
Danuglipron, developed by Pfizer, is a small molecule GLP-1 receptor agonist, tested in over 1,600 people. It was originally developed for twice-daily oral administration and demonstrated an average weight loss of 8% to 13% over 32 weeks in the phase 2b trial. However, due to poor tolerance, the formulation was not advanced to phase 3.
Will the improved dosing schedule for danuglipron be successful? Bourla admitted he is "very cautious" about it, saying, "I have been burned, and I don't want to create false expectations, either positive or negative."
Albert Bourla CEO of Pfizer
Analysts predict that the weight loss market could exceed $120 billion in the next decade. With Eli Lilly and Novo Nordisk taking the lead, Pfizer's attempt to enter the obesity space with a small molecule approach is understandable.
As Bruce Booth, a partner at the well-known U.S. venture capital firm Atlas Venture, put it: "Fundamentally, it's hard for pharmaceutical companies to stay out of this space right now. It's a major growth driver for the industry, and if you're not in it, you'll fall behind."
Oral therapies, with their lower production costs, convenience, and suitability for long-term maintenance after rapid weight loss, have become another battleground for major pharmaceutical companies. Among them, Novo Nordisk's oral semaglutide has completed phase 3 studies on weight loss, followed by Eli Lilly's orforglipron, which it acquired from Chugai and is now in phase 3 clinical trials. Other contenders include Roche's CT-996, acquired from Carmot, and AstraZeneca's ECC-5004, which it acquired from Cheng Yi Biotech.
Facing the large weight loss market, Pfizer has not put all its eggs in one basket. Danuglipron is just one of the drugs in its weight loss pipeline. The team is also developing oral small molecule GLP-RA drug PF-06954522 and GIPR antagonist PF-07976016, both of which are in early clinical stages. Additionally, Pfizer is seeking potential BD opportunities.
"I don't think GLP injectables will interest us at this point, as it might be a bit late from a BD perspective. But for other mechanisms of action, whether injectable or oral, we are indeed conducting a thorough market investigation because I believe we have the ability to develop and commercialize them," Bourla said.
In 2023, Pfizer's performance was affected by a significant reduction in sales of its COVID-19 products, with annual revenue dropping by 42% to $58.49 billion. However, the situation improved in 2024, particularly with a 32% year-over-year increase in Q3 revenue to $17.7 billion. The company has raised its full-year 2024 revenue guidance to $61 to $64 billion.
In the new year, Bourla considers advancing R&D and product lines as Pfizer's "top priority", with plans to launch 13 phase 3 studies, 8 of which are expected to yield critical data this year.
Apart from weight loss products, Bourla also highlighted four potential oncology drugs: the CDK4 inhibitor atirmociclib (PF-07220060), the IB6 ADC (sigvotatug vedotin, PF-08046047) and PD-L1 ADC (PF-08046054) from Seagen, and the BCMA/CD3 bispecific antibody Elrexfio.
The arrival of CDK4/6 inhibitors has opened a new chapter in breast cancer treatment. However, under the pressure from Novartis and Eli Lilly, Pfizer's first CDK4/6 inhibitor, Ibrance, is losing its first-mover advantage. Can the selective CDK4 inhibitor atirmociclib become a new growth point for Pfizer?
Bourla explained that CDK4 produces therapeutic effects, while CDK6 causes most of the toxicity. Therefore, a CDK4 inhibitor can minimize toxicity. Atirmociclib has undergone high-dose escalation studies, with 90% of patients exceeding 85% of the maximum dose, and its good safety profile makes it a promising first-line treatment option.
The new ADC, sigvotatug vedotin, was described by Bourla as a "super bomb". The IB6 protein targeted by it is abundantly expressed in various cancers. Currently, the product is undergoing phase 3 studies for second-line treatment of non-small cell lung cancer (NSCLC) and early studies for first-line treatment of head and neck cancer.
PF-08046054, a PD-L1-targeted ADC, is in a phase 1 trial for head and neck cancer. Unlike immunotherapies that interfere with PD-1 and PD-L1 interactions, this product aims to identify and attack cancer cells with PD-L1. It has also shown anti-cancer activity in animal models with low PD-L1 expression.
Elrexfio was approved in the U.S. in August 2023 for the treatment of fourth-line and beyond relapsed or refractory multiple myeloma. Bourla believes it is a best-in-class therapy that offers durable remission, with no median progression after three years of treatment. The product is also undergoing several phase 3 trials to expand its indication.
It is worth noting that Pfizer will face a "wave of loss of exclusivity (LOE)" in the next few years, which could result in the company losing around $17 billion to $18 billion annually. To counter this threat, Pfizer is addressing it through a series of acquisitions. Bourla stated that the products acquired by the company are expected to generate $20 billion in revenue by 2030.
