[Edaily Reporter KIM SAE-MI ] "Lirapugratinib" (RLY-4008), a bile duct cancer treatment for which HLB INC.(028300)has secured global commercialization rights, has received approval from the U.S. Food and Drug Administration (FDA). While the first-line liver cancer treatment combination of “riboceranib” and “camrelizumab” had been rejected by the FDA three times, “lirapugratinib”—a separate pipeline candidate—has succeeded in entering the U.S. market first.

FDA Approves Two Days Ahead of Review Deadline… “Ripictu” Enters U.S. Market

On the 23rd (local time), the FDA approved lirapugratinib as a treatment for adult patients with unresectable, locally advanced, or metastatic cholangiocarcinoma who have previously received treatment and have FGFR2 gene fusions or other rearrangements. Although the original review deadline under the Prescription Drug User Fee Act (PDUFA) was set for the 25th, the FDA issued its approval decision two days earlier.

The brand name is “LYRFIGTU.” Previously, on the 22nd, the FDA had conditionally accepted “LYRFIGTU” as the brand name, and with this marketing authorization, the brand name has been finalized. The recommended dosage is 70 mg administered orally once daily.

Specific postmarketing requirements (PMR) and postmarketing commitments (PMC) can be confirmed once the approval Seohan is made public. The FDA has announced that it plans to post LYRFIGTU’s full prescribing information on its drug approval database.

Ripictu is an oral targeted anticancer drug that selectively inhibits fibroblast growth factor receptor 2 (FGFR2), which is involved in the development and growth of cancer. Unlike existing FGFR-class therapies, which broadly inhibit FGFR1 through FGFR4, Ripictu is designed to selectively inhibit FGFR2, thereby minimizing off-target inhibition of other FGFRs. The FDA has designated Ripictu as a breakthrough therapy and an orphan drug, and in March of this year, it granted priority review status to the New Drug Application (NDA).

The global Phase 1/2 trial (ReFocus), which formed the basis for approval, was conducted in 116 patients with unresectable or metastatic cholangiocarcinoma who had previously received chemotherapy or chemoimmunotherapy but had no prior experience with FGFR inhibitors. The objective response rate (ORR), as assessed by an independent review committee, was 45.7%, and the median duration of response (mDOR) was 11.8 months. According to Eleva, the median progression-free survival (mPFS) was 11.3 months, and the 12-month progression-free survival rate was 49.2%.

Currently, FDA-approved treatments for cholangiocarcinoma in the same class include Insight’s “Pemazyre” (femigatinib) and Daiho Oncology’s “Litgov” (putibatinib). Given that Rifictu positions its FGFR2 selectivity as a key differentiator, the key question is how it will compete with existing treatments in the real-world prescribing market.

According to safety information released by the FDA, major warnings and precautions included ocular toxicity, hyperphosphatemia and soft tissue calcification, and embryo-fetal toxicity. Among the 385 patients treated with Rifictu, retinal pigment epithelium detachment (RPED) occurred in 31%, and hyperphosphatemia in 21%. Serious adverse events were observed in 32% of patients.

Approved by

the FDA Before the New Liver Cancer Drug… Eleva to Commercialize It Directly

From HLB INC.’s perspective, this approval is particularly significant as it stands in contrast to the outcome for its new liver cancer drug. Eleva had sought FDA approval for a first-line treatment for liver cancer using a combination of riboceranib and camrelizumab, developed by China’s Hengrui Pharmaceuticals, but received three Complete Response Seohans (CRLs) in May 2024, March 2025, and July of this year. Ripictu is a separate development program with different manufacturing facilities and an approval package from the new liver cancer drug.

HLB emphasized, “This approval marks the first instance in which a Korean pharmaceutical and biotech company has directly submitted a New Drug Application (NDA) for a global anti-cancer drug to the FDA and received approval.” Following its acquisition of the worldwide development and commercialization rights for lirapugratinib from U.S.-based Relay Therapeutics in December 2024, Eleva has led the formulation of the approval strategy, the submission of the NDA, and interactions with the FDA.

Lirapugratinib was not a compound discovered by HLB INC. itself. Eleva acquired the candidate compound, which had been under development by Relay. The deal is valued at up to $500 million (approximately 683.8 billion won), and Relay is eligible to receive milestone payments tied to regulatory and commercialization milestones, as well as tiered royalties based on global sales.

As of the end of June, Relay had received a total of $18.7 million (25.6 billion won) from Eleva, consisting of an upfront payment of $5 million (6.8 billion won), $3.7 million (5.1 billion won) for the transfer of active pharmaceutical ingredients and other materials, and $10 million (13.7 billion won) in milestone payments. The specific amounts of the regulatory milestones associated with this FDA approval have not been disclosed.

Eleva plans to launch Refictu in the U.S. in the fourth quarter of this year. Having secured FDA approval, the company is expected to accelerate the actual commercialization process, including distribution and insurance coverage in the U.S. Eleva, HLB INC.’s U.S. subsidiary, will directly lead the commercialization of Refictu.

Kim Dong-geon, CEO of Eleva, stated, “The FDA approval of Ripictu signifies that we are providing an important second-line treatment option for cholangiocarcinoma patients and their families,” adding, “We will do our utmost to ensure the drug is made available to healthcare providers and patients as quickly as possible.”

The company is also set to expand into global markets, starting with the U.S. This month, Eleva initiated the European approval process by submitting a Marketing Authorization Application (MAA) for Ripictu as a treatment for cholangiocarcinoma to the European Medicines Agency (EMA). If approval is secured in Europe following the U.S., Ripictu’s commercial reach is expected to expand significantly. Jin Yang-gon, Chairman of HLB INC., expressed confidence, saying, “Since we have manuals and organizational structures in place that we prepared in anticipation of the approval of a new liver cancer drug, a rapid launch will be possible.”

Efforts to expand the drug’s indications are also underway. Eleva is conducting a global clinical trial (ReFocus202) targeting patients with various solid tumors harboring FGFR2 fusions or rearrangements. This is a “tumor-agnostic” development strategy that screens patients based on FGFR2 gene abnormalities rather than specific cancer types.

Chairman Jin emphasized, “The greatest appeal of anticancer drugs is that successfully developing a single drug opens up the possibility of expanding its indications.” He added, “Refictu can now expand its indications beyond cholangiocarcinoma to various other cancer types, and the path has also been opened to further broaden the scope of treatment through combination therapy with anticancer drugs held by big pharma.”