[Edaily Reporter Kim Seung-kwon ] The largest-ever patent cliff is looming over the global pharmaceutical and biotech markets. This is because the expiration dates for the exclusive rights to global mega-blockbuster drugs—which previously generated annual sales ranging from several trillion to tens of trillions of won—are arriving en masse starting this year. Consequently, a full-scale battle is expected to erupt between global Big Pharma, seeking to defend its stronghold, and domestic biosimilar and generic drug companies aiming to break into that market and secure new cash cows.

In particular, the race is intensifying between Samsung Bioepis and Celltrion—the two giants of the global biosimilar industry—as they target the autoimmune disease and anticancer drug markets, including Keytruda, the world’s top-selling immuno-oncology drug, as well as Stelara and Prolia. E-Daily’s pharmaceutical and biotech premium content platform, Pharm E-Daily, has conducted an in-depth analysis of the hidden dynamics behind the “patent cliff” that is heating up the pharmaceutical market in the second half of this year, as well as the strategies of the key beneficiary companies.

The Era of Blockbusters and the Patent Cliff Is Upon Us... Which Drugs Are Gaining Attention?

According to the Korea Pharmaceutical and Bio-Pharma Manufacturers Association on the 4th, starting this year, the total value of expiring patents for global blockbuster

drugs

will easily exceed $200 billion—or 270 trillion won—by 2030. In terms of quantity, some 200 biopharmaceuticals are set to lose patent protection over the next 10 years. For global Big Pharma companies, this represents a survival crisis where 30–50% of their revenue could vanish in the short term; however, for companies that have long been honing their biosimilars and generics, it signals the opening of the largest goldmine in pharmaceutical history.

First and foremost, the global pharmaceutical industry’s attention is firmly focused on Merck (MSD)’s immuno-oncology drug Keytruda (active ingredient: pembrolizumab). Keytruda is known as a mega-blockbuster that currently holds the undisputed top spot in global sales among individual pharmaceutical products. Last year, Keytruda’s sales surpassed $31.7 billion (approximately 43 trillion won), setting a new all-time record.

In effect, a single drug generates more revenue than half of South Korea’s national defense budget. The key U.S. substance patent for this colossal drug is set to expire in 2028. The patent expiration of the top-selling drug is considered a megaton-level event that will shake up the entire anticancer drug market.

The disruptive impact of drugs for which the patent expiration countdown has already ended or is currently underway is also beyond imagination. In fact, in the case of Johnson & Johnson’s (J&J) autoimmune disease treatment Stelara (active ingredient: ustekinumab, with annual sales of approximately 15 trillion won), sales of the original drug are plummeting as biosimilars have recently begun entering the market in the U.S. and Europe in earnest, timed to coincide with the patent expiration.

According to Johnson & Johnson’s first-quarter earnings report this year, Stellara’s quarterly sales plummeted by nearly 60% year-over-year due to the impact of biosimilars, demonstrating the devastating impact of the patent cliff. In addition, Eylea (active ingredient: aflibercept, annual sales of approximately 12 trillion won), a treatment for age-related macular degeneration held by Regeneron and Bayer, and Prolia (active ingredient: denosumab, annual sales of approximately 9 trillion won), Amgen’s osteoporosis treatment, are also seeing their core exclusive rights expire, sparking fierce competition among biosimilar companies.

Furthermore, a massive market is opening up not only in the field of biopharmaceuticals—which require sophisticated cell culture—but also in the area of chemically synthesized drugs (small-molecule drugs). Pfizer’s breast cancer treatment Ibrance (active ingredient: palbociclib) is a representative blockbuster targeted anticancer drug that recorded annual sales of over $5 billion (approximately 7.6 trillion won) during its peak.

With the patent for Ibrance’s key active ingredient set to expire next March, it is considered the most attractive target for pharmaceutical companies with expertise in the oncology field. Pfizer and Bristol-Myers Squibb (BMS), which compete for the top one or two spots in global sales, are also facing the expiration of a key patent barrier in 2027 for their anticoagulant “Eliquis” (annual sales of approximately 16 trillion won).

Looking at past cases, the impact of the patent cliff becomes even clearer. In the case of AbbVie’s autoimmune disease treatment Humira, which had long held the top spot in global sales, original sales plummeted by more than 30% in just one year as soon as its U.S. patent expired and biosimilars flooded the market. The trillions of won in revenue that vanished into thin air were fully converted into confirmed earnings for the biosimilar companies that had secured a head start in the market.

An industry insider in the biosimilar sector stated, “Since the market set to open next year and beyond will be several times larger than the Humira situation, the industry’s attention is focused on prepared first movers capable of efficiently capturing market share from the originator,” adding “While the past was a period when biosimilars proved their potential through products like Remsima and Humira biosimilars, the second act will be a decisive battle as patents for mega-blockbuster immuno-oncology drugs like Keytruda begin to expire in earnest,” the source explained.

Korea’s Pharmaceutical and Biotech Sector: Which Companies Will Benefit from Patent Expirations?

Domestic biosimilar developers are employing a division-of-labor strategy that maximizes each company’s unique strengths and infrastructure, rather than engaging in cutthroat competition. In the highly complex and large-scale antibody biopharmaceutical market, Samsung Bioepis and Celltrion(068270)are gaining a foothold through a head-on approach. In the chemical synthesis anticancer drug market, where barriers to entry differ, Boryung(003850)is reaping substantial benefits through a meticulous patent-avoidance strategy.

First, Samsung Bioepis is pursuing a strategy of expanding its market presence by replicating off-patent drugs the fastest and on the largest scale, leveraging its unparalleled process know-how in conducting simultaneous global multi-country clinical trials and its solid financial strength.

Samsung Bioepis recently demonstrated the effectiveness of this strategy by preemptively commercializing Afilibu (U.S. name: Opuviz), a biosimilar of Eylea. Samsung Bioepis became the first Korean company to obtain marketing authorization from the U.S. Food and Drug Administration (FDA). In the domestic market, in partnership with SamilPharmaceutical(000520), the company has seen a steep upward trajectory in prescription sales since its initial launch.

In its push for Keytruda, Samsung Bioepis recently demonstrated equivalence to the originator drug by meeting the pharmacokinetic (PK) endpoint criteria for the primary evaluation in a global Phase 1 clinical trial of its Keytruda biosimilar. Samsung Bioepis is also aggressively advancing a global Phase 3 clinical trial under the project name “SB27.” This is interpreted as an effort to be the first in the world to bring the product to market on the very day the U.S. patent expires in 2028.

Furthermore, Samsung Bioepis has successfully launched its Stelara biosimilar (SB17), which had already seen declining sales, thereby completing the world’s largest biosimilar portfolio spanning autoimmune diseases, anticancer drugs, ophthalmic diseases, and endocrine disorders.

A Samsung Bioepis official stated, “The positive results confirmed in the Phase 1 clinical trial of SB27, a biosimilar of a blockbuster immunotherapy, are highly significant as they demonstrate our world-class R&D capabilities.”

Celltrion(068270)The company has taken a bold strategic gamble by adopting a “biobetter” strategy—which goes beyond simple replication to deliver innovative value that surpasses the originator drug—and by establishing a global direct-to-consumer sales network that completely eliminates distribution commissions. Celltrion is proceeding smoothly with patient dosing for the global Phase 3 clinical trial of “CT-P51,” a biosimilar of Keytruda. Celltrion is also successfully navigating the regulatory approval process for “CT-P41,” a biosimilar of the osteoporosis treatment Prolia.

Particularly noteworthy is the innovation in its revenue structure. Moving away from a model where a significant portion of sales was paid out as commissions to local distribution partners, the company has fully established a direct sales system by setting up its own subsidiaries in the U.S. and Europe and deploying its own sales force. This is also why the surging trillions of won in biosimilar sales are directly translating into higher operating profit margins for Celltrion without any commission leakage.

While the two giants of the domestic biosimilar industry are engaging in head-to-head battles with global Big Pharma in the massive biopharmaceutical arena, Boryung—the pride of traditional Korean pharmaceutical companies—is reaping substantial profits by wielding a sharper scalpel than anyone else in the chemical synthesis blockbuster market.

Boryung has perfectly targeted the market for Ibrance, Pfizer’s massive 6 trillion won breast cancer treatment, whose patent expires next year. It has precisely tapped into a multi-trillion won niche that antibody biotech companies have avoided entering because it involves a chemical drug with a different manufacturing process. For several years, Boryung has been at the forefront of patent litigation, including a patent scope confirmation trial, to invalidate the core substance patent for Ibrance. Ultimately, Boryung, along with other mid-sized domestic pharmaceutical companies, emerged victorious in its patent avoidance efforts.

As a result, Boryung has secured the right of first refusal to launch a generic version of Ibrance on the very day its core patent expires next March, allowing it to immediately capture the market for the original drug. If Boryung’s proprietary oncology sales network—already seamlessly established across the nation’s hospital network—generates synergy with this new product, the Ibrance generic is expected to become Boryung’s mega cash cow immediately upon launch.

However, some argue that a sober assessment to separate the wheat from the chaff is necessary from a long-term perspective. This is because, with a golden opportunity worth hundreds of trillions of won now open, not only domestic companies but also large Indian pharmaceutical firms with substantial capital and multinational companies specializing in biosimilars from the U.S. and Europe are fiercely entering this market.

A securities firm analyst stated, “The upcoming patent cliff in 2027–2028 will be a historic turning point for domestic biotech companies to elevate themselves to the status of true global players,” adding “Rather than investing based on vague expectations that a company is ‘developing a blockbuster biosimilar,’ it is time to place medium- to long-term trust in companies that demonstrate their fundamentals with concrete numbers—such as how well their Phase 3 clinical data is recognized at global academic conferences and whether U.S. FDA approval milestones are being achieved as planned,” he emphasized.