Much like Humira to AbbVie, Merck is inseparably linked to Keytruda in the public eye.

Since its first FDA approval in 2014, Keytruda has dominated the PD-1 inhibitor landscape and rapidly become Merck’s mainstay. As the drug expanded its indications across various solid tumors, its revenue quickly surpassed $20 billion and topped the global bestseller list in 2023.

By that time, however, Keytruda accounted for more than 40% of the company’s total revenue—and it suddenly became clear that the “blockbuster king” was approaching a patent cliff.

Merck had disclosed that two major compound patents for Keytruda would expire in 2028. Notably, during the 2025 earnings call, Davis sent a positive signal: the company was increasingly confident of extending the validity of these two patents to 2029.

How significant is that one-year difference? Roughly $30 billion.

In 2025, Keytruda generated $31.68 billion in revenue for Merck, a 7% year-on-year rise. It maintained a strong position across core indications such as non-small cell lung cancer and triple-negative breast cancer, with continued advancement into earlier treatment lines remaining its primary growth driver.

Yet the issue was not “whether growth exists” but “what that growth signifies.” A 7% growth rate marked a sharp slowdown from Keytruda’s peak years—when sales rose 19% in 2023.

Double-digit growth was no longer sustainable over the long term. As major indications matured, Keytruda was shifting from an “expansion product” to a cash-generating asset requiring careful stewardship.

Against this backdrop, Davis struck a balanced tone. He stated plainly that whether Keytruda lost exclusivity in 2028 or 2029, Merck’s transformation strategy would remain unchanged: the company could no longer rely solely on Keytruda.

In fact, Merck had already launched a “product evolution” strategy for Keytruda.

Central to this strategy was Keytruda Qlex, a subcutaneous formulation. Compared with the original 30-minute intravenous infusion, the new formulation reduced administration time to approximately two minutes.

This shift also extended the drug’s patent lifecycle, potentially turning a steep cliff into a gradual decline. Merck has filed hundreds of patents for Keytruda overall; those covering the subcutaneous formulation are expected to extend market exclusivity through 2042.

Meanwhile, Merck is exploring new combination regimens for Keytruda.

In January, Merck and Moderna released five-year follow-up data from the Phase IIb KEYNOTE-942 trial: compared with Keytruda monotherapy, the combination of Keytruda and the personalized mRNA cancer vaccine intismeran autogene (mRNA-4157/V940) reduced the risk of recurrence or death by 49% in patients with high-risk melanoma.

Merck is not alone in pursuing combination therapies. Led by Akeso Biotech, a wave of PD-(L)1/VEGF bispecific antibodies has emerged.

At the 2024 World Conference on Lung Cancer (WCLC), Akeso Biotech presented results from the HARMONi-2 study: in first-line treatment for PD-L1-positive non-small cell lung cancer, ivonescimab extended median progression-free survival from 5.82 months (with Keytruda) to 11.14 months, cutting the risk of disease progression or death by 49%.

This marked the world’s first PD-(L)1/VEGF bispecific antibody to defeat Keytruda head-to-head in a Phase III trial.

In the fourth quarter of 2025, Summit Therapeutics, Akeso’s partner, formally submitted a new drug application for ivonescimab to the FDA. The filing was recently accepted, with a regulatory review deadline set for November 14.

The “post-Keytruda era” has arrived for Merck, and it is unstoppable.

In the latest earnings call, Davis once again laid out Merck’s promising future.

“We have never been more confident in our ability to deliver significant growth as we approach the expiration of Keytruda’s patents,” he stressed, forecasting that Merck’s annual revenue would surpass $70 billion by the “mid-2030s.”

The biggest difference from the “Keytruda era” is that this time, Merck is not searching for a “next blockbuster king.”

Keytruda’s success stemmed largely from favorable industry tailwinds: the explosion of immunotherapy, rapid expansion of indications, and a regulatory environment highly supportive of innovative oncology drugs. Today, however, nearly all major multinational corporations (MNCs) recognize that replicating a single super-blockbuster has grown exponentially harder.

As such, Merck’s vision for $70 billion centers on building a diversified growth model.

Winrevair clearly has blockbuster potential. Launched in the U.S. in March 2024, the novel pulmonary arterial hypertension (PAH) drug generated $419 million in sales within just over half a year. In 2025, Winrevair delivered on expectations, posting revenue of $1.4 billion.

Dean Li, President of Merck Research Laboratories, reaffirmed during the earnings call that Winrevair was “redefining the standard of care for pulmonary arterial hypertension.”

Until at least 2024, PAH remained a life-threatening, incurable disease that long plagued the industry. Yet even symptom-modifying therapies spawned multiple commercial blockbusters—for instance, vasodilators now represent a $6-billion market. As a novel-mechanism agent, Winrevair opens new therapeutic avenues for PAH patients and fresh revenue streams for Merck.

According to FactSet, analysts project Winrevair sales will exceed $5.5 billion by 2030—more than $400 million above 2024 estimates.

Cantor analysts offered an even higher peak sales range: $8 billion to $8.5 billion, with up to $2 billion expected to come from indications beyond those already approved.

In November 2025, Winrevair succeeded in a Phase II trial designed to evaluate its ability to improve pulmonary blood flow in certain heart failure patients with hypertension. Merck’s stock rose 3.4% following the release of interim data.

Another emerging growth driver is Ohtuvayre, a new chronic obstructive pulmonary disease (COPD) drug. It alone contributed $178 million in revenue in the fourth quarter. Jefferies analysts predict Ohtuvayre will reach peak annual sales of $3 billion to $4 billion by the mid-2030s.

In contrast to Winrevair and Ohtuvayre, enlicitide—still in clinical development—serves a distinct strategic role.

Mechanistically, enlicitide is not a disruptive innovation but a highly commercially oriented product. In the established PCSK9 inhibitor market, efficacy is well-proven; the main barrier to broader adoption is long-term patient adherence to injectable therapy. Enlicitide’s oral formulation aims to redefine access in a validated market.

Poised to become the “first oral PCSK9 inhibitor,” enlicitide succeeded in two Phase III trials in June 2025. Merck plans to file for U.S. approval in early 2026, potentially ushering in a new era of cholesterol-lowering therapies.

Further ahead, Merck is doubling down on its long-standing infectious disease business with CD388.

CD388 is a single-dose, universal prophylactic agent active against all influenza strains. Granted FDA Breakthrough Therapy Designation, CD388 is on track for accelerated review, with a potential launch as early as 2028.

Davis described CD388 as a “key growth driver for Merck over the next decade,” with a commercial opportunity exceeding $5 billion.

Combined, these assets make the $70-billion target a result of diversified growth rather than reliance on a single product. Merck insists that “nearly all” of its 20+ new growth drivers have blockbuster potential: oncology exceeding $25 billion, cardiometabolic care over $20 billion, and infectious diseases above $15 billion.

Merck’s transformation is unlikely to be achieved entirely through internal development.

A 2024 Deloitte report noted that R&D efficiency among the world’s top 20 pharmaceutical MNCs has continued to decline in recent years, hitting a decade-low in 2022 with an R&D return on investment of just 1.2%.

This low return reflects soaring R&D costs: the average cost to develop a new drug now stands at $2.284 billion. For a large-cap company seeking to mitigate risk, capture opportunities, and sustain growth, external deals are essential.

Notably, many of Merck’s key pipeline assets—from Keytruda to the newer therapies supporting its $70-billion story—originated through acquisitions.

Unlike some peers, Merck had previously avoided multi-billion-dollar acquisitions while Keytruda was in its high-growth phase. As Keytruda’s patent cliff loomed, however, the company’s stance on M&A shifted—not toward risky bets, but toward strategic, tool-like transactions.

Two multibillion-dollar deals in 2025—for Verona Pharma and Cidara Therapeutics—epitomized this approach.

Both acquisitions shared key traits: targets were not early-stage conceptual assets but programs with clear clinical pathways; indications were well-defined and complementary to Merck’s existing pipeline; and crucially, both would contribute meaningful revenue around the time of Keytruda’s patent expiration, helping offset the cliff risk.

This signaled a shift in M&A’s role within Merck: from an expression of long-term vision to a pragmatic response to time pressure. Merck’s decision to walk away from talks with Revolution Medicines reinforced this logic.

In January, reports emerged that Merck had pursued a takeover of Revolution Medicines. A source familiar with the matter stated that the parties had discussed a purchase price of $28 billion to $32 billion—potentially the largest pharma deal since Pfizer’s $43-billion acquisition of Seagen.

Revolution Medicines focuses on therapies targeting RAS mutations. Acquiring the biotech’s pipeline would have opened new frontiers in Merck’s oncology portfolio.

The FDA has recognized Revolution’s progress: in 2025, doraxonrasib received Breakthrough Therapy Designation and was selected for the FDA’s new Center Director National Priority Voucher (CNPV) pilot program, potentially supporting accelerated approval as early as late 2026.

After weeks of speculation, however, Merck halted the acquisition process, with high valuation a major factor.

During its third-quarter 2025 briefing, Merck emphasized that it would pursue strategic acquisitions and capital allocation to drive future growth, targeting deal sizes ranging from $1 billion to $15 billion. At the recent J.P. Morgan Healthcare Conference, the company signaled a near-term focus on deals under $15 billion.

This cautious approach was also reflected in its 2026 financial guidance: projected sales of $65.5 billion to $67 billion, falling short of analyst expectations.

Leo Tolstoy wrote in Anna Karenina that “all unhappy families are unhappy in their own way.” For pharmaceutical MNCs in transition, however, the patent cliff dilemma is universal. Data from American Bazaar shows that the industry may face the worst market exclusivity loss in history between 2025 and 2030.

Against this backdrop, M&A will remain a dominant theme. Among peers facing similar pressures, whether Merck can carve out its own path to success may become clear sooner rather than later.