Like many huge pharma corporations presently, Merck’s greatest problem within the subsequent few years is the patent cliff. Merck has spent years getting ready for the lack of exclusivity dealing with Keytruda, however the scale of the issue continues to develop. Keytruda and its subcutaneous formulation Keytruda Qlex generated round $31.7 billion in 2025, practically half of Merck’s complete gross sales, whereas key U.S. patents defending pembrolizumab are on account of start expiring in 2028. The drug remains to be increasing into new most cancers settings and recorded double-digit progress within the first quarter of 2026.
Merck’s current dealmaking means that it doesn’t count on one other drugs to interchange Keytruda by itself. In October 2025, the corporate accomplished its roughly $10 billion acquisition of Verona Pharma, gaining Ohtuvayre, an already marketed therapy for persistent obstructive pulmonary illness. It adopted in January 2026 with the $9.2 billion acquisition of Cidara Therapeutics and its part 3 influenza-prevention candidate MK-1406, earlier than agreeing in March to pay roughly $6.7 billion for Terns Prescribed drugs and the clinical-stage persistent myeloid leukemia drug TERN-701.
Shopping for property after a few of their improvement danger has fallen is hardly distinctive to Merck. With patent expiries approaching throughout the pharmaceutical trade, giant drugmakers are searching for merchandise that may attain the market shortly sufficient to assist their present companies. Merck’s rising technique is extra distinctive in the way in which these acquisitions match round a number of more and more concentrated portfolios. Ohtuvayre joins Winrevair and enlicitide in cardio-pulmonary drugs; Merck’s TERN-701 provides to a rising hematology pipeline; and MK-1406 enhances an infectious illness portfolio more and more centered on long-acting therapy and prevention.
The focus downside Keytruda created
When the U.S. Meals and Drug Administration (FDA) first authorized Keytruda in 2014, its use was restricted to sufferers with superior melanoma who had already acquired different therapies. The PD-1 inhibitor subsequently expanded throughout quite a few tumor varieties, therapy strains and mixtures, transferring from superior illness into earlier settings the place immunotherapy is given earlier than or after surgical procedure.
Keytruda will not be behaving like a mature product approaching patent expiry but. Gross sales rose one other 12% yr on yr to roughly $8 billion within the first quarter of 2026. Demand continued to extend each in metastatic cancers and in earlier-stage indications similar to triple-negative breast, cervical and renal cell cancers. The franchise remains to be turning into bigger even because the interval through which Merck can depend on it’s shorter.
Merck expects biosimilar competitors to start affecting Keytruda materially between 2028 and 2029. Its main U.S. compound patent expires in December 2028, though two associated composition-of-matter patents prolong into 2029. European market exclusivity is anticipated to final till 2031.
There are additionally pressures elsewhere within the portfolio. Gardasil and Gardasil 9 gross sales fell 39% to roughly $5.2 billion in 2025, largely due to decrease demand and extra stock in China. Merck had paused shipments to the nation in February 2025 and later prolonged that pause by the tip of the yr.
Newer merchandise are starting to broaden the income base, however they stay removed from Keytruda’s scale. Winrevair gross sales virtually doubled yr on yr to $525 million within the first quarter of 2026, whereas the lately launched Keytruda Qlex generated $128 million.
Keytruda isn’t an bizarre patent expiry because it has been, and nonetheless is, Merck’s progress engine. Merck has to unwind a enterprise mannequin through which one drugs provides virtually half of the corporate’s income, whereas its second-largest franchise has additionally change into much less reliable.
Cardio-pulmonary drugs turns into Merck’s clearest second pillar
Amongst Merck’s companies past oncology, cardio-pulmonary drugs presently appears to be the clearest new progress pillar taking form. Winrevair has established a specialist franchise in pulmonary arterial hypertension, Ohtuvayre has added an already marketed respiratory drug, and the current approval of enlicitide provides Merck an entry into the a lot bigger ldl cholesterol market.
Winrevair has supplied the strongest early validation. Merck gained sotatercept by its $11.5 billion acquisition of Acceleron in 2021, earlier than the drug was authorized for pulmonary arterial hypertension (PAH). Launched within the U.S. as Winrevair in March 2024, it generated $1.4 billion in 2025, its first full yr in the marketplace.
The drug can be transferring past the inhabitants that supported its preliminary approval. Within the part 3 trial, Winrevair diminished the chance of demise, lung transplantation, or PAH-related hospitalization in sufferers with superior illness, supporting an expanded U.S. indication in October 2025.
Winrevair resembles the acquisition mannequin Merck is making an attempt to repeat elsewhere: purchase a clinically superior asset, then enhance its worth by extra trials, indication enlargement, and international commercialization.
Ohtuvayre broadens Merck’s place into respiratory illness. Merck acquired the drug with Verona Pharma after its U.S. launch for the upkeep therapy of persistent obstructive pulmonary illness (COPD). The product generated $178 million for Merck between the completion of the acquisition in October and the tip of 2025, whereas Winrevair continues to broaden in uncommon pulmonary illness.
Enlicitide extends the pillar towards a mass cardiovascular market. Accredited by the FDA this week as Lipfendra, it’s the first oral PCSK9 inhibitor, providing a once-daily pill towards a goal beforehand addressed by injectable antibodies.
In part 3, enlicitide lowered LDL ldl cholesterol by 56% in contrast with placebo at 24 weeks. It additionally outperformed established oral non-statin choices, together with ezetimibe and bempedoic acid.
Injectable PCSK9 therapies have demonstrated that the mechanism can produce substantial LDL reductions, however an oral model could also be simpler to introduce alongside statins and extra enticing to some sufferers and prescribers. A every day capsule will not be essentially simpler to stick to than an injection given each few weeks, and pricing and reimbursement will strongly affect uptake.
Merck’s oncology pipeline fragments past Keytruda
Keytruda’s patent expiry doesn’t mark the tip of Merck’s oncology technique. The corporate is utilizing the years earlier than biosimilar competitors arrives to reshape its most cancers enterprise round a number of applied sciences quite than a single immunotherapy. Whereas Keytruda stays the industrial engine, Merck is extending its attain into antibody-drug conjugates (ADCs), focused therapies and customized most cancers vaccines, making a portfolio that’s broader, but in addition extra fragmented.
The corporate continues to maneuver Keytruda into earlier phases of illness, the place sufferers are handled earlier than or after surgical procedure. On the similar time, the launch of the subcutaneous formulation, Keytruda Qlex, gives a extra handy various to intravenous administration and will assist protect the franchise as biosimilars method. Keytruda additionally stays Merck’s most well-liked mixture associate, permitting the corporate to pair its established checkpoint inhibitor with a lot of its next-generation oncology property.
The second a part of the technique has been constructed largely by exterior innovation and offers. Merck has assembled one of many trade’s broadest ADC portfolios by partnerships with Kelun-Biotech and Daiichi Sankyo, for example. These collaborations give the corporate entry to a number of targets, tumor varieties, and payload applied sciences, whereas permitting Keytruda to be evaluated alongside a number of of them. An instance of that is Merck’s $700 million financing settlement with Blackstone Life Sciences to assist the event of sacituzumab tirumotecan (sac-TMT).
On the similar time, Merck is investing in property that might finally stand independently of PD-1 inhibition. Welireg is a industrial instance of a focused remedy outdoors immuno-oncology, whereas Merck’s acquisition of Terns added TERN-701 in persistent myeloid leukemia to a rising hematology pipeline that additionally consists of bomedemstat, nemtabrutinib and zilovertamab vedotin. In the meantime, its collaboration with Moderna on the customized most cancers vaccine intismeran autogene is one other diversification past typical checkpoint inhibition, even when this system presently depends upon mixture with Keytruda.
Merck’s oncology enterprise is turning into extra diversified, however not essentially much less depending on Keytruda. A lot of its most promising applications are nonetheless designed to enrich the checkpoint inhibitor quite than substitute it outright.
Can Merck’s immunology pipeline repeat the Keytruda playbook?
Merck’s rising immunology technique is about whether or not it could actually take a single mechanism and prolong it throughout a number of illnesses, because it beforehand did with PD-1 inhibition. Its $10.8 billion acquisition of Prometheus Biosciences in 2023 was largely a guess on tulisokibart, an antibody concentrating on TL1A, a protein concerned in inflammatory and fibrotic pathways. The deal additionally added Prometheus’s genetics and biomarker capabilities.
That funding acquired its most necessary validation in June 2026, when the part 3 ATLAS-UC induction trial met its main and key secondary endpoints in ulcerative colitis. Tulisokibart induced medical remission and improved endoscopic and histological measures after 12 weeks, making it the primary anti-TL1A antibody to report optimistic part 3 leads to the illness.
Merck is growing tulisokibart as greater than an ulcerative colitis therapy. A part 3 program is underway in Crohn’s illness, whereas earlier-stage trials in rheumatological, dermatological and fibrotic circumstances together with rheumatoid arthritis, hidradenitis suppurativa and systemic sclerosis-associated interstitial lung illness are underway.
The corporate can be starting so as to add different immunology mechanisms across the Prometheus platform. Its settlement with Dr. Falk Pharma secured international rights to the early-stage anti-CD30L antibody MK-8690 for $150 million upfront.
Pembrolizumab helped set up a brand new therapeutic class after which expanded quickly throughout tumor varieties. TL1A is already a aggressive subject, with Sanofi and Teva’s duvakitug in part 3, Roche growing afimkibart, and different corporations pursuing next-generation antibodies. Merck might have secured an early lead with the primary optimistic part 3 readout, however constructing a significant immunology franchise will depend upon whether or not tulisokibart can distinguish itself.
Merck’s infectious illness pipeline: A quieter technique
The muse of Merck’s infectious pipeline is islatravir, which reached the U.S. market in April 2026 with Idvynso, a once-daily mixture with doravirine for virologically suppressed adults. Merck is now making an attempt to increase the identical molecule into much less frequent regimens. Its once-weekly mixture with Gilead’s lenacapavir produced optimistic part 3 leads to June 2026, whereas one other weekly mixture with ulonivirine is in part 2b improvement.
Merck can be wanting in the direction of prevention. Alimatravir, a separate long-acting compound, is in part 3 as a once-monthly oral PrEP capsule. Present oral PrEP could be extremely efficient when taken constantly, however its real-world safety depends upon adherence. A month-to-month pill might significantly scale back the therapy burden.
Merck is making use of related logic to influenza by CD388, the central asset in its $9.2 billion acquisition of Cidara. The long-acting antiviral is being developed as a single-dose preventive supposed to guard high-risk individuals throughout an influenza season, no matter their immune response. It’s now in part 3.
Merck after Keytruda: a broader portfolio
Merck’s response to the approaching Keytruda patent cliff is now seen. It’s assembling a number of franchises that might collectively assist the corporate throughout oncology, cardio-pulmonary drugs, immunology, and infectious illness.
Winrevair and Ohtuvayre give Merck two differentiated cardio-respiratory merchandise. Tulisokibart might anchor a brand new immunology franchise. ADCs, focused therapies and customized vaccines are increasing oncology past PD-1 inhibition, whereas Merck’s infectious illness applications share a quieter technological emphasis on longer-lasting therapy and prevention.
But Merck’s diversification on the pipeline degree doesn’t imply diversification on the income degree. Keytruda and Keytruda Qlex generated $31.7 billion in 2025, near half of Merck’s complete gross sales. Gardasil contributed one other $5.2 billion regardless of its sharp decline in China. By comparability, the corporate’s newer merchandise are nonetheless measured in tons of of tens of millions or low single-digit billions.
Merck now wants a number of applications to succeed throughout completely different illnesses, improvement phases, and industrial fashions. That technique has additionally been costly. Merck paid $10.8 billion for Prometheus, $10 billion for Verona, and $9.2 billion for Cidara, whereas persevering with to commit substantial capital by licensing agreements and oncology collaborations. These investments present entry to differentiated science, however in addition they place larger strain on Merck to broaden indications, combine acquired property, and commercialize these property.
The corporate has diminished the chance of relying on one scientific mechanism by rising its dependence on dealmaking and portfolio execution. The post-Keytruda Merck could also be broader and extra resilient, however it is going to even be extra difficult and fewer reliant on one product, and extra reliant on dozens of medical, regulatory, and industrial selections going sufficiently properly on the similar time.
