Merck & Co.’s Keytruda is the world’s best-selling drug and has been a cancer juggernaut for more than a decade, scoring its 40th indication in June and adding yet another in late September.
As such, Keytruda accounted for about 42% of the company’s sales in 2023, which is a lot of weight to bear for a tentpole drug teetering on the edge of a patent cliff. That’s why the pharma giant is boosting the rest of its portfolio to ready itself for a world in which Keytruda will start facing biosimilar competition as early as 2028.
“Our pipeline is broadening. I think that is an important part of thinking about the future of Merck beyond 2028,” said Dr. Joerg Koglin, Merck’s senior vice president and head of general medicine and global clinical development. “General and specialty medicine will play an important role in that.”
He called 2024 “a year with momentum” and categorized 2025 as a year “where we have a number of major deliverables” such as study readouts and additional filings “that all seem to be on track.”
Cardiometabolic pipeline
Front and center is Merck’s cardiometabolic pipeline, which the company anticipates will yield seven potential approvals by 2030, leading to peak revenue potential of more than $15 billion by the mid-2030s, the company told PharmaVoice.
Merck already scored an FDA nod in March with the breakthrough biologic Winrevair, a first-in-class treatment for pulmonary arterial hypertension. Importantly, the approval doesn’t restrict access to Winrevair based on functional class, which means physicians can prescribe it to patients outside phase 3 study criteria, according to analysts.
“It is a very broad label, which just indicates for us that the regulators agree with … our perception of how meaningful the data is,” Koglin said.
Koglin calls that approval “chapter one” for Winrevair. Now, the company is trying to expand the label further. For instance, he pointed to a second phase 3 study that was so successful it was stopped early. The study was investigating whether Winrevair could reduce the risk of death, lung transplantation or hospitalization in patients with advanced PAH.
“It was the first PAH clinical study that was ever stopped for overwhelming efficacy,” he said.
Merck is also exploring Winrevair’s use in just-diagnosed PAH patients and is “advancing nicely,” while another trial is looking at its use in heart failure patients who develop pulmonary hypertension — the data should read out before year end, he said.
“Merck is investing a lot into general and specialty medicine, and many of those assets have development timelines that could lead to approvals that fall somewhere into this space before initial Keytruda patent expiry."
Dr. Joerg Koglin
SVP, head, general medicine and global clinical development, Merck & Co.
Beyond Winrevair, Koglin said Merck will also read out its first pivotal study of its oral PCSK9 inhibitor to lower cholesterol in 2025. Currently, the class of drugs is only available in higher-priced injectables.
The daily pill, called MK-0616, is “an oral solution that might have a risk-benefit profile comparable to injectables, that come, obviously, with a promise that you can reach a much broader population,” Koglin said.
Other emerging areas
While Merck’s late-stage pipeline leans overwhelmingly toward cancer, the company is dipping its toe in other emerging clinical areas as well. Koglin points to pipeline momentum and business development through acquisitions over the last few years in areas like immunology, neuroscience and ophthalmology.
“Merck is investing a lot into general and specialty medicine, and many of those assets have development timelines that could lead to approvals that fall somewhere into this space before initial Keytruda patent expiry,” he said.
The pharma giant has been busy on the M&A front.
He pointed to Merck’s March acquisition of the ophthalmology company EyeBio and the advancement of a phase 2b/3 trial of a potentially first-in-class treatment for diabetic macular edema. He also noted Merck’s April 2023 acquisition of immunology company Prometheus Biosciences and its lead inflammatory bowel disease asset. In addition, Merck acquired the neurodegenerative disease company Caraway Therapeutics in November 2023.
The company also took steps into the GLP-1 space last month by entering into a global license deal with Hansoh Pharma for a preclinical, oral small molecule GLP-1 receptor agonist.
“I think you’ll see that GLP-1 will move from injectable to oral therapies,” Koglin said. “We have a smart discovery group, and we are using business development to figure out, as the chapters evolve from injectables, where Merck’s opportunity is to be part of something that’s really well differentiated.”
Merck’s focus on cancer will continue, including advancing a subcutaneous version of Keytruda, but Koglin said the company is “excited” about its broadening pipeline.
“Lots seem to be on track,” he said.
