[Edaily Reporter KIM SAE-MI ] Few people know the U.S. Food and Drug Administration (FDA) approval process for “Ripicto” (generic name: lirapugratinib) as thoroughly as Jang Seong-hun, former vice president of Eleva Therapeutics. After gaining extensive experience in new drug review and regulatory affairs at the U.S. FDA, he moved to Eleva, a U.S. subsidiary of HLB INC., as vice president, where he was in charge of new drug development and approval strategies. One of his final tasks at Eleva was to personally submit the New Drug Application (NDA) for “Ripicto” to the FDA.

During his meeting with E-Daily at the office in Mapo-gu, Seoul, on the 28th, former Vice President Jang assessed this approval as an event that goes beyond simply being “HLB INC.(028300)’s first FDA new drug approval.” This is because, although Eleva submitted the New Drug Application (NDA) based on single-arm clinical data with Accelerated Approval in mind, the FDA granted Standard Approval without imposing any separate confirmatory clinical trial requirements.

Former Vice President Jang said, “Even within Eleva, we naturally assumed we would receive Accelerated Approval,” adding, “Until the very end, the biggest point of interest was how the FDA would handle this.”

Pioneering Drugs

Face

Consecutive Setbacks in Confirmatory Trials… FDA Grants Exception for Rifictuene

The approval of Rifictuene was driven by the difficulties encountered by earlier FGFR2 inhibitors in their confirmatory trials. Incyte’s “Pemazyre” (femigatinib) and Taiho Oncology’s “Litgovi” (putibatinib) each received FDA accelerated approval in 2020 and 2022, respectively, but faced difficulties—including patient recruitment—while conducting their confirmatory trials. QED Therapeutics’ “Truseltic” (infigratinib) received FDA accelerated approval in 2021 but ultimately voluntarily withdrew its approval and exited the market.

Elevado faced the same problem immediately after introducing “Ripictu.” To obtain accelerated approval, the company had to prepare a confirmatory clinical trial to demonstrate clinical benefit, but it was practically difficult to recruit hundreds of patients with the rare FGFR2 mutation to conduct a randomized trial.

Former Vice President Jang recalled, “We explained to the FDA that confirmatory trials for existing FGFR2 inhibitors were facing difficulties and discussed what kind of trial should be conducted,” adding, “Surprisingly, the FDA postponed specific discussions regarding the confirmatory trial until after approval.”

He noted, “It was quite exceptional that the FDA accepted an NDA based on accelerated approval without having specifically determined the confirmatory trial,” adding, “Although the NDA submission was delayed by a few months while we discussed this issue, it would have taken much longer if we had designed and initiated the confirmatory trial before submitting the application.”

Full

Approval Based on a Single-Arm Trial… “Will Set the Benchmark for Future FGFR2 Approvals”

The biggest twist came with the final approval. Repicto was approved based not on a randomized Phase 3 trial, but on a single-arm Phase 1/2 clinical trial (ReFocus) involving 116 patients with cholangiocarcinoma who were previously treated but had not received an FGFR inhibitor. The objective response rate (ORR) was 46%, and the median duration of response (mDOR) was 11.8 months.

Former Vice President Jang noted, “This is a historic event even from the perspective of the FDA, the regulatory authority,” adding, “This is because the FDA decided to grant full approval—rather than accelerated approval—based on the ORR and DOR data from a single-arm trial.”

He cited treatment efficacy and the practical limitations of confirmatory trials as the reasons behind the full approval. Former Vice President Jang explained, “While an ORR of 46% is not overwhelmingly higher than that of competing drugs, it is by no means a bad result,” adding, “I view this as a decision made after comprehensively considering the entire dataset, including unmet medical needs, treatment efficacy, the feasibility of confirmatory trials, and the value of information that could be obtained through additional clinical trials.”

With the burden of a confirmatory trial lifted by the full approval, both costs and time have been significantly reduced. According to former Vice President Jang, the cost of a recent anticancer drug clinical trial is approximately $200,000 per patient. Conducting a trial with 100 participants would therefore cost about $20 million (approximately 27.3 billion won).

Former Vice President Jang also highlighted the potential for Rifictu to become a new benchmark for future FGFR2 therapeutic development. Another benefit of this full approval is that it has established a favorable market position by raising the bar for latecomers seeking approval.

He predicted, “While existing drugs were approved under accelerated approval and could not be considered established standard-of-care treatments, Repicto’s full approval means it can serve as a reference point for future FGFR2 therapies,” adding, “It will become increasingly difficult for subsequent drugs to gain approval based solely on single-arm clinical trials, as in the past, and they will likely need to demonstrate clinical value compared to Repicto.”

Beyond Technology Export to Direct Approval and Sales… Expanding the K-Bio New Drug Development Model

This approval is also significant in that it expands the

new drug development

model for the domestic biotech industry.

Previously, Yuhan Corporation’s new lung cancer drug “Lazertinib” received FDA approval in 2024, but the global rights outside of Korea were licensed to Janssen, which 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, directly conducted late-stage development and the FDA approval process, and will also handle sales in the U.S.

Former Vice President Jang emphasized, “In the past, we would have licensed the technology to a global pharmaceutical company during the late stages, but now we’ve demonstrated a new model where domestic companies can conduct late-stage clinical development on their own,” adding, “The significance of Ripictu lies not only in HLB INC.’s first FDA approval but also in this achievement.”

Jin Yang-gon, Chairman of the HLB INC. Group, also mentioned via YouTube on the day of approval, “I believe it is more progressive to secure an anticancer drug on our own and propose, ‘Let’s develop our anticancer drug in combination with yours,’ rather than entrusting the company’s fate to Big Pharma after licensing the technology to them.”