[Edaily Reporter KIM SAE-MI ] While HLB INC.(028300)has successfully obtained U.S. Food and Drug Administration (FDA) approval for “Ripicto” (active ingredient: lirapugratinib), a new drug for cholangiocarcinoma, analysts say that the true test of its commercial success lies ahead. This is because the U.S. market for second-line cholangiocarcinoma treatment—which Ripicto is entering—is not particularly large, and two FGFR inhibitors have already established a strong foothold in the market.

For Ripicto to generate meaningful revenue, the key will be not only how much market share it can take from the market leaders but also how quickly it can expand into the European market and into indications beyond bile duct cancer.

8,000

Annual Cases of Bile Duct Cancer in the U.S. … The FGFR2-Positive Second-Line Market Is Even Narrower

According to the biotech industry on the 27th, the FDA approved Ripictu, developed by HLB INC.’s U.S. subsidiary Elevate Therapeutics, on the 23rd (local time) as a treatment for adult patients with previously treated, unresectable, locally advanced, or metastatic bile duct cancer harboring an FGFR2 gene fusion or other rearrangement.

The number of patients for whom Ripicto is immediately available following FDA approval is quite limited. Bile duct cancer is a rare cancer that occurs in the ducts through which bile flows; according to the American Cancer Society (ACS), approximately 8,000 new cases of bile duct cancer are diagnosed in the United States each year. Even this figure combines cases of both intrahepatic and extrahepatic bile duct cancers.

The FGFR2 fusion targeted by Rifictu is known to be found primarily in intrahepatic cholangiocarcinoma. The National Cancer Institute (NCI) reports that FGFR2 gene fusions occur in about 15% of intrahepatic cholangiocarcinoma cases.

Furthermore, since Ripicto is intended for patients who have received prior treatment, only a fraction of the 8,000 new bile duct cancer patients each year will actually qualify for approval. Considering that FGFR2 abnormalities must be confirmed through molecular testing, the actual prescription market could be even narrower.

Facing

Competition from Two Rival Drugs… What Weapons Will It Use to Capture Market Share

? Moreover, the market Ripictu is entering is not uncontested. Incyte’s “Pemazyre” (femigatinib) received FDA approval in 2020, and Taiho Oncology’s “Litgovi” (putibatinib) also received approval in 2022. Pemazyre is indicated for previously treated FGFR2-fusion or -rearranged cholangiocarcinoma, while Ritgovi is indicated for intrahepatic cholangiocarcinoma with the same genetic abnormality.

Last year, Pemazyre—the first-to-market drug—posted net product sales of $86.73 million (approximately 118 billion won), a 6% increase from the previous year’s $81.75 million (111 billion won). This figure represents Pemazyre’s total net product sales, not just revenue generated from bile duct cancer in the U.S. Nevertheless, the presence of the first-to-market drug, which has already accumulated several years of prescribing experience, is expected to pose a significant barrier to entry for the latecomer, Ripicto.

Commercialization capabilities are also a key variable. Eleva holds the global commercialization rights for Rifictu and is preparing for its U.S. launch in the fourth quarter of this year. Since experience with new drug approvals and local sales and marketing capabilities are distinct areas, Eleva’s commercialization capabilities—including the speed at which it builds a prescribing network, secures insurance coverage, and establishes a distribution network—are expected to determine the pace of initial market penetration.

Ripictu’s key strengths are its efficacy and FGFR2 selectivity. Among the 116 patients evaluated by the FDA as the basis for approval, Ripictu’s objective response rate (ORR) was 46%, and the median duration of response (mDoR) was 11.8 months. At the time of Ritgo’s approval, the ORR was 42% and the mDoR was 9.7 months. Pemazyre also had an ORR in the 30% range at the time of its approval.

Another distinguishing feature of Ripictu is that it is designed to minimize inhibition of other FGFR subtypes and selectively target FGFR2. According to Eleva, the incidence rates of hyperphosphatemia and diarrhea in the Ripictu clinical trial were 20.7% and 21.6%, respectively. The company is highlighting the potential for high FGFR2 selectivity to reduce the side effects typically seen with non-selective FGFR inhibitors.

Kim Dong-geon, CEO of Eleva, stated, “Lirapugratinib has established a remarkable clinical profile that sets it apart from existing treatment options.”

Another point worth noting is that Ripictu is a step ahead of its competitors from a regulatory perspective. Pemazaire and Ritgov are currently under FDA accelerated approval and still require follow-up trials to confirm their clinical benefits. In contrast, although Ripictu received approval based on Phase 1/2 clinical data, it entered the market with full approval rather than accelerated approval.

Unlike competing drugs, whose continued approval depends on the results of confirmatory clinical trials, Ripictu stands out by having alleviated this regulatory uncertainty. While competing drugs must demonstrate actual therapeutic efficacy through follow-up clinical trials after market entry, Ripictu is not subject to such conditions. Given that patient recruitment is difficult due to the nature of rare cancers, making it challenging to conduct confirmatory trials in the first place, this is a significant advantage for commercialization.

Limitations of Focusing Solely on Cholangiocarcinoma… Expanding into Europe and Targeting All Cancer Types

Ripictu’s market potential depends on how successfully it can move beyond the narrow market of cholangiocarcinoma. This month, Eleva submitted a marketing authorization application to the European Medicines Agency (EMA) for Ripictu as a treatment for cholangiocarcinoma with FGFR2 fusions or rearrangements. The strategy is to expand the patient pool by extending sales into Europe, following the U.S. market.

Efforts to expand indications are also underway. Eleva is currently conducting the global Phase 2 clinical trial “ReFocus202” in patients with solid tumors other than bile duct cancer that harbor FGFR2 fusions or rearrangements. Starting in South Korea and the U.S., the company is conducting clinical trials in the U.K., Spain, France, and other countries, pursuing a “tumor-agnostic” strategy that broadens the patient population based on the presence of FGFR2 gene abnormalities rather than specific cancer types.

Jin Yang-gon, Chairman of HLB INC., emphasized, “ReFocus202 has now moved beyond being a treatment for cholangiocarcinoma and can be expanded to various cancer types, and the path has been opened to diversify indications through combination development with anticancer drugs held by big pharma,” adding, “The approval of this new drug for cholangiocarcinoma is not the end, but the beginning.”