[Edaily Reporter KIM SAE-MI ] HLB INC.(028300)has cleared the U.S. Food and Drug Administration (FDA) hurdle for the first time. This comes after the company had suffered three consecutive setbacks with its new liver cancer drug, a combination therapy of riboceranib and camrelizumab; its bile duct cancer treatment “Ripictu” (active ingredient: lirapugratinib) was the first to secure marketing approval.

Although the market that “Ripictu” targets is not large at the moment, from HLB INC.’s perspective, this signifies that the company has secured its first new drug to generate global revenue and is now able to actively operate its local commercialization organization in the U.S. If this leads to expansion into Europe and tumor-agnostic indications—and eventually to the approval of a new drug for liver cancer—Ripictu is expected to serve as the “first step” in launching HLB GLOBAL Co., Ltd.’s global oncology business. Furthermore, some analysts view this as a case that takes the K-Bio new drug development model—which had previously centered on technology exports—to the next level.

First FDA-Approved New Drug… Elevado Transforms from a “Drug Development Company” to a “Commercialization Company”

According to the biotech industry on the 28th, the FDA approved Rifictu on the 23rd (local time) as a treatment for adult patients with previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements. HLB INC.’s U.S. subsidiary, Elevate Therapeutics, is preparing for a U.S. launch in the fourth quarter of this year.

Ripicto is the first new drug from the HLB INC. pipeline to receive FDA approval. This achievement is significant because Elevate secured the global development and commercialization rights for Ripicto from U.S.-based Relay Therapeutics in December 2024 and subsequently obtained approval through a direct NDA submission and FDA review.

With the approval of Ripictu, the nature of Eleva’s business will also change. Until now, Eleva has primarily functioned as a new drug developer responsible for the clinical trials and approvals of Riboceranib and Ripictu, but it is now entering the commercialization phase by directly selling its products in the U.S. With the U.S. launch of the Riboceranib and Camrelizumab combination therapy and Rifictu in mind, Eleva has been preparing its local sales infrastructure, including expanding its team dedicated to insurance reimbursement and market access.

If Ripictu is launched first, this organization can be tested in real-world prescription, reimbursement, and distribution processes. Given that cancer centers and medical oncology departments specializing in gastrointestinal tumors—which treat both cholangiocarcinoma and hepatocellular carcinoma—are the primary customers, there is a high likelihood that the sales and marketing infrastructure can be shared if the combination therapy with Riboceranib eventually receives FDA approval.

Furthermore, Ripictu represents a significant milestone for K-Bio’s global anti-cancer drug development efforts. Although “Lazertinib,” a new lung cancer drug developed by Yuhan(000100), received FDA approval in 2024, Janssen—which acquired global rights excluding Korea—led the U.S. NDA submission, approval, and commercialization. In contrast, for Ripictu, HLB INC.’s U.S. subsidiary, Eleva, secured global development and commercialization rights and will directly handle everything from late-stage clinical development to NDA submission, FDA approval, and U.S. sales.

As this marks the first instance in which a domestic pharmaceutical or biotech company has taken a new anticancer drug—for which it secured global rights—all the way to the FDA approval stage and is proceeding with commercialization in the U.S., some observers view this as a significant expansion of the K-Bio new drug development model, which had previously been centered on technology exports. A biotech industry official commented, “This approval demonstrates that domestic biotech companies are capable of conducting late-stage clinical development on their own,” adding, “It is significant in that it shows a new possibility: that companies can go beyond technology exports to handle everything from in-house development to approval and commercialization.”

Applied for Accelerated Approval but Received ‘Full Approval’… Regulatory Status Also Sets It Apart

A particularly noteworthy aspect of this approval is the type of approval granted. Eleva submitted its New Drug Application (NDA) expecting to receive Accelerated Approval based on the tumor response confirmed in a single-arm clinical trial. However, the FDA ultimately granted Full Approval rather than Accelerated Approval.

Jang Seong-hoon, former vice president at Eleva who was directly in charge of submitting the NDA for Ripicto, explained that the difficulties faced by earlier FGFR2 therapies in their confirmatory trials influenced this decision.

In fact, Incyte’s “Pemazyre” (femigatinib) and Taiho Oncology’s “Litgovi” (putibatinib) received FDA Accelerated Approval in 2020 and 2022, respectively. They currently remain under Accelerated Approval status, with post-marketing requirements still pending to verify their clinical benefit. QED Therapeutics’ “Truseltic” (infigratinib) requested voluntary withdrawal after facing difficulties recruiting patients for its confirmatory clinical trial, and its approval was ultimately revoked in 2024.

The Phase 1/2 clinical trial (ReFocus) that served as the basis for approval was a single-arm study, not a randomized Phase 3 trial. In 116 patients with cholangiocarcinoma who were FGFR inhibitor-naïve but had received prior treatment, the objective response rate (ORR) was 46%, and the median duration of response (mDOR) was 11.8 months.

With the obligation to confirm clinical benefit—a requirement for drugs granted accelerated approval—removed, Rifictu has gained a regulatory edge over its competitors. Pemazire and Ritgov still hold accelerated approval status and face the challenge of providing further evidence of clinical benefit. In contrast, Rifictu received full approval from the outset, thereby reducing such regulatory uncertainty.

This approval is expected to raise the bar for subsequent entrants and create a barrier to entry. Former Vice President Jang predicted, “With Rifictu receiving full approval, it could become a benchmark for future FGFR2 therapies,” adding, “It will become more difficult for subsequent drugs to gain approval based solely on single-arm clinical trial results, as was the case in the past, and it is increasingly likely that they will need to demonstrate additional clinical value compared to Rifictu.”

The U.S. bile duct cancer market is small… The key battlegrounds are Europe and expansion across all cancer types

It is difficult to expect Repicto to generate large-scale sales immediately. Approximately 8,000 new cases of bile duct cancer are diagnosed annually in the U.S. Among these, FGFR2 fusions and rearrangements occur primarily in intrahepatic bile duct cancer, accounting for only about 10–15% of cases. Since Repicto also requires patients to have “prior treatment experience,” the actual patient population eligible for treatment is even narrower.

The fact that Pemazyre and Ritgov have already secured a foothold in the market is also a challenge. While Ripictu was designed to selectively inhibit FGFR2 and demonstrated its potential for differentiation by achieving an ORR of 46% in the ReFocus trial, it remains to be seen how much market share it can capture from competing drugs. In the early U.S. market, market share is expected to hinge on safety and tolerability related to FGFR2 selectivity, actual prescribing experience, insurance coverage, and access to patient screening tests.

In the medium to long term, expanding indications and sales regions beyond the narrow U.S. cholangiocarcinoma market is essential to increase Rifictu’s value. Eleva has already submitted a marketing authorization application for Rifictu to the European Medicines Agency (EMA) on the 15th. At the same time, it is conducting a global Phase 2 clinical trial targeting patients with FGFR2 fusions or rearrangements in solid tumors, excluding cholangiocarcinoma. The strategy is to secure a “tumor-agnostic” indication—where the drug is prescribed based on the presence of FGFR2 mutations, regardless of the cancer’s location.

For this reason, it is difficult to gauge the value of this FDA approval based solely on Rifictu’s initial sales figures. For HLB INC., this achievement not only establishes a track record as the group’s first FDA-approved new drug but also enables the company to actually launch its direct sales system in the U.S., while creating additional growth drivers through expansion into Europe and broader indications. Furthermore, if the combination therapy of riboceranib and camrelizumab—a first-line treatment for liver cancer that received its third Complete Response Letter (CRL)—succeeds in obtaining FDA approval following a resubmission, Eleva could establish itself as the outpost for HLB INC.’s U.S. oncology business, selling new drugs for both cholangiocarcinoma and liver cancer simultaneously.

Therefore, the recent approval of Rifictu is not so much the final destination of HLB INC.’s long-standing goal of “U.S. new drug approval” as it is the starting point for the company’s transition from a global new drug developer to the commercialization phase. The next key point to watch will be how HLB translates this first approval into actual U.S. sales and how it builds on that success to secure a second new drug approval and expand Rifictu’s geographic reach and indications.