Boryung(003850) tore down the last patent barrier that had blocked the monotherapy market for the blockbuster anticancer drug "Lenvima (ingredient lenvatinib mesylate)" generics. After successive wins in a patent dispute with global drugmaker Eisai that began in 2022, it also neutralized the use patent for differentiated thyroid cancer.

But the real battle starts now. That is because a combination therapy patent remains for using Lenvima together with MSD's immuno-oncology drug "Keytruda (ingredient pembrolizumab)." Boryung lost at the Intellectual Property Trial and Appeal Board stage in this patent fight and is now waging a second round at the Intellectual Property High Court.

There is a reason Boryung is challenging even the combination therapy patent. In cancer drug development and treatment, the share of combination therapy using multiple drugs is growing. The U.S. National Cancer Institute (NCI) analyzed 465 phase 1 clinical trials for solid tumors from 2000 to 2019, and found that 69% were combination therapies using two or more treatments.

Lenvima, too, has expanded its use through combination therapy. It is used as monotherapy in differentiated thyroid cancer and hepatocellular carcinoma, but in endometrial cancer and renal cell carcinoma, a regimen administered together with Keytruda is used.

This expansion of combination therapy is also evident in Lenvima's global business. According to Eisai, Lenvima sales reached $1.51 billion (about 2.14 trillion won) for the fiscal year ending Mar. 2025. Eisai cites as a key driver of recent years' Lenvima sales growth the U.S. Food and Drug Administration (FDA) approvals of its combination with Keytruda in first-line renal cell carcinoma and some second-line endometrial cancer.

Boryung's Lenvanib, the generic (copy drug) of Eisai's blockbuster cancer therapy Lenvima./Courtesy of Boryung

◇ From use to composition to formulation… successive neutralization of Lenvima follow-on patents

The Intellectual Property High Court recently ruled against the plaintiff in Eisai's lawsuit seeking to overturn the decision invalidating the use patent for an "antitumor agent for thyroid cancer" filed against Boryung. After receiving the ruling on the 27th of last month, Eisai did not file an appeal within the prescribed period, and the ruling was finalized on the 11th. The patent was set to remain in force until Mar. 2028.

Boryung has challenged various follow-on patents surrounding Lenvima. It filed invalidation trials or scope confirmation trials targeting crystal form patents, formulation patents, and composition patents, and also won cases that went up to the Supreme Court. In Mar., it also targeted the patent "method for suppressing bitterness of quinoline derivatives," which was not listed in the Ministery of Food and Drug Safety patent list, and obtained a decision of partial acceptance and partial dismissal.

Among these, the patent Boryung viewed as most important was the composition patent that had been scheduled to remain in force until Aug. 2035. Boryung judged that even if all other patents were cleared, the risk to product sales would not be resolved as long as this patent remained. With the invalidation of this patent finalized in Aug. last year, some analysts say it effectively shortened the original drug's de facto exclusivity by about 10 years.

Including this thyroid cancer use patent, Boryung said it is "in a state where all patents have been circumvented or invalidated." At least for monotherapy in indications such as thyroid cancer and hepatocellular carcinoma, this means patents are no longer a factor blocking generic prescriptions.

A view of the Intellectual Property High Court in Seo District, Daejeon./Courtesy of Intellectual Property High Court

◇ 'Launch first' worked… rising share for lenvatinib, but full-fledged sales not yet

Boryung won marketing approval last Feb. for "lenvatinib" 4 mg, 10 mg, and 12 mg, and launched the product in Jul. the same year. All three dosages were also listed for national health insurance coverage.

How was that possible with the patent dispute still unresolved?

That is because the Ministery of Food and Drug Safety's review of a generic's quality and equivalence to grant marketing approval is a separate matter from whether the product infringes an existing patent. In particular, unlisted patents not entered in the MFDS patent list are not subject to the marketing approval–patent linkage system and therefore do not, by themselves, block the approval or sale of a generic.

The finalization of the thyroid cancer use patent likewise is more meaningful as a ruling that resolved lingering legal uncertainty after launch, rather than one that enabled the launch.

Since launch, lenvatinib has been gradually settling into the market. According to the pharmaceutical industry data analysis platform BRP Insight, lenvatinib's market share steadily rose from 1.0% in Dec. last year to 6.5% in Jan. this year and 12.9% in Feb.

However, it is expected to take more time before substantial sales materialize. Boryung is currently proceeding with procedures to register the product with general hospital pharmacy and therapeutics committees. A Boryung official said, "It typically takes six months to more than a year to complete hospital-by-hospital registration procedures," adding, "We expect sales to hit their stride after this process is completed."

Endometrial cancer starts in the endometrium, the tissue lining the inner wall of the uterus. Because early symptoms such as abnormal bleeding are pronounced, it is often detected early. When diagnosed early, a hysterectomy alone can be curative./Courtesy of Mayo Clinic

◇ Capture the "Keytruda combination" market… Boryung's second round at the Intellectual Property High Court

According to the 2023 National Cancer Registration Statistics from the Ministry of Health and Welfare and the Korea Central Cancer Registry, Korea had 3,813 new endometrial cancer patients and 7,367 new kidney cancer patients. About 94% of kidney cancers are known to be renal cell carcinoma.

That is why Boryung, just two months after the Lenvima–Keytruda combination therapy patent was registered, simultaneously filed an invalidation trial and a negative scope confirmation trial in Jun. 2024. One move argues "this patent itself is invalid," and the other seeks confirmation that "our product does not fall within this patent's scope of rights."

But in Apr., the Intellectual Property Trial and Appeal Board did not accept Boryung's claims. Boryung has appealed and filed a lawsuit at the Intellectual Property High Court to overturn the decision.

Boryung has already obtained approval for Keytruda combination therapy in endometrial cancer and renal cell carcinoma. However, as long as the patent protecting that regimen remains in force, merely being listed in the approved indications does not mean it can freely market for those indications.

Boryung plans to continue the lawsuits while seeking additional opportunities to enter the market. At the same time, it will pursue expansion of monotherapy market share by emphasizing dosing convenience.

To that end, Boryung added a 12 mg strength to lenvatinib that Lenvima does not have. A Boryung official explained, "The initial dosing for hepatocellular carcinoma is 12 mg, so if only 4 mg and 10 mg Lenvima are used, patients must take three 4 mg capsules," adding, "Cancer patients often take other medications together, so there was clinical demand to reduce this burden."

However, regarding the core issues the company is contesting in the combination therapy patent suit and the likelihood that the Intellectual Property High Court will overturn the Intellectual Property Trial and Appeal Board's decision, it said, "It is difficult to comment as the matter is ongoing," declining to elaborate.

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