Even as Keytruda’s patent nears its expiration, the world’s best-selling drug is still chalking up clinical wins.
At last week’s gathering of the European Society for Medical Oncology, Merck & Co. presented on the blockbuster’s positive performance in combination with Padcev from Pfizer and Astellas in a recent trial, which halved overall deaths for patients with muscle-invasive bladder cancer.
But even as the checkpoint inhibitor continues to demonstrate transformational power, its financial supremacy is waning. Sales of the drug, which comprised nearly half of Merck’s sales last year, totaling $29.5 billion, are expected to peak around $32.7 billion next year, and then begin a slow slide as it loses ground to biosimilar competition, according to analyst forecasts.
This fall’s launch of a subcutaneous version of the drug, Keytruda Qlex, a faster, easier-to-administer alternative, is expected to bolster Merck’s bottom line. Analysts predict the reformulation could reach roughly $7 billion in sales in the early 2030s.
Even so, Merck is still under substantial pressure from investors to make up the difference. The company is now banking on a strong pipeline, including numerous oncology candidates, to help put it on firm footing in the future.
The company has 16 anti-cancer drugs in 60 ongoing registrational phase 3 trials. These include immunotherapy treatments like Keytruda that target the body’s immune response to malignancies and shut down pathways that fuel tumor growth.
The company also recently bought into one high-interest area in oncology, inking a deal to gain an exclusive global license to develop, manufacture and commercialize the PD-1/VEGF bispecific antibody LM-299 from Shanghai-based LaNova Medicines. One drug has already shown early potential to rival Keytruda. While LM-299 is still in early-phase testing, it gives Merck a foothold in this potentially game-changing area.
“We are positioned for long-term leadership in oncology as we continue to diversify and deepen our pipeline,” said Robert Davis, chairman, president and CEO of Merck, on a February 2025 earnings call.
Here are three other Merck oncology contenders that could help stem pending Keytruda losses.
Sacituzumab tirumotecan (sac-TMT)
Merck has thrown much of its weight behind the development of antibody-drug conjugates, including sac-TMT, which it licensed from Sichuan Kelun-Biotech. The drug targets trophoblast-cell surface antigen 2, and Merck is testing it in 11 different types of cancer, including six phase 3 indications, such as breast, ovarian and lung cancer.
The candidate has racked up some recent successes. It reduced the risk of disease progression or death by 65% in breast cancer patients with previously treated, locally advanced or metastatic hormone-receptor positive and human epidermal growth factor negative disease, compared with chemotherapy. It also led to a 51% risk reduction in disease progression and death compared with chemotherapy in a China-based trial for patients with EGFR-mutated non-small cell lung cancer, according to interim data.
Sac-TMT is being tested alone and in combination with Keytruda, but it remains to be seen if these favorable results can hold up amid further testing.
Raludotatug deruxtecan
Another antibody drug conjugate Merck is co-developing with Daiichi Sankyo recently saw favorable results in a phase 2 ovarian cancer trial, posting a more than 50% objective response rate in platinum-resistant disease. Women in the study group would normally expect to see a 20% to 30% response rate if they were treated using the standard of care.
The drug candidate received a breakthrough designation from the FDA and is now moving into phase 3 in ovarian cancer with mid-stage studies ongoing in 10 other indications. One of the challenges it could face is the increasingly crowded ADC market, which could grow to $40 billion by 2029.
MK-1084
MK-1084 is an oral selective KRAS G12C inhibitor that the company is testing in combination with Keytruda in non-small cell lung cancer and colorectal cancer.
“KRAS is among the most prevalent mutations in cancer and KRAS G12C is the most common KRAS mutation in patients with non-small cell lung cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, in a press release. “Based on early evidence showing MK-1084 in combination with Keytruda had a manageable safety profile and promising anti-tumor activity, we are now proceeding to a larger phase 3 trial to evaluate this combination in certain patients with metastatic non-small cell lung cancer.”
The drug candidate is also in phase 3 for colorectal cancer, but will face substantial competition from companies such as Amgen’s Lumakras and Bristol Myers Squibb’s Krazati.
