HLB's Elevar Submits EMA Marketing Application for Lirafugratinib in FGFR2-Driven Cholangiocarcinoma
核心洞察
Elevar Therapeutics (搜索) filed a marketing authorization application with the European Medicines Agency (搜索) for lirafugratinib as a second-line treatment for FGFR2 (搜索)-driven advanced or metastatic cholangiocarcinoma (搜索).
The filing rests on global Phase 1/2 data showing a 46.5% objective response rate, 11.8-month median duration of response, 11.3-month median PFS and 22.8-month median OS.
Lirafugratinib's selective FGFR2 (搜索) inhibition yielded hyperphosphatemia and diarrhea rates of 20.7% and 21.6%, which the company cites as differentiated tolerability versus first-generation FGFR inhibitors.
HLB (搜索)'s U.S. subsidiary Elevar Therapeutics (搜索) has submitted a marketing authorization application (MAA) to the European Medicines Agency (搜索) for lirafugratinib as a second-line treatment for patients with advanced or metastatic cholangiocarcinoma (搜索) harboring FGFR2 (搜索) fusion or rearrangement mutations, the company announced on the 15th. The application was filed on the 14th, marking the start of the drug candidate's European approval process and following an earlier filing in the United States.
The simultaneous push in the world's two largest regulatory markets comes as the U.S. Food and Drug Administration (搜索)'s final review deadline for lirafugratinib approaches on the 25th of this month. Elevar submitted a new drug application to the FDA in January of this year, and the drug is currently under priority review under the Prescription Drug User Fee Act.
Phase 1/2 Efficacy Data Underpin Both Filings
The EMA application is based on results from a global Phase 1/2 trial conducted by Elevar. In patients with FGFR2 (搜索) fusion-positive advanced or metastatic cholangiocarcinoma (搜索) who had received at least one prior systemic therapy, lirafugratinib produced an objective response rate of 46.5%.
Median duration of response was 11.8 months, median progression-free survival was 11.3 months, and median overall survival was 22.8 months.
Selective FGFR2 Inhibition and Tolerability
Lirafugratinib is an oral, small-molecule targeted anticancer agent designed to selectively inhibit FGFR2 (搜索), one of the genetic mutations that drive cancer. According to the company, the drug differs from previously approved first-generation FGFR inhibitors that broadly block FGFR1, 3 and 4 and can cause side effects such as hyperphosphatemia and diarrhea.
In clinical trials, the incidence rates of hyperphosphatemia and diarrhea — considered representative adverse events of FGFR inhibitors — were 20.7% and 21.6%, respectively, data the company cites as underscoring a differentiated tolerability and safety profile.
"Lirafugratinib is a novel drug candidate that has demonstrated clinically meaningful efficacy and differentiated safety data consistent with its high FGFR2 (搜索) selectivity and sustained inhibition mechanism," said Kim Dong-geon, CEO of Elevar Therapeutics (搜索). "We will proceed with the regulatory approval process in the United States and the European Union without disruption, while expanding the therapeutic potential of lirafugratinib to various solid tumors through tumor-agnostic clinical trials."
Regulatory History and Tumor-Agnostic Expansion
Lirafugratinib is an asset Elevar acquired from Relay Therapeutics in 2024, securing global development and commercialization rights. The FDA granted the drug orphan drug designation in 2022 and breakthrough therapy designation in 2023.
Beyond cholangiocarcinoma (搜索), HLB (搜索) and Elevar are running a global Phase 2 trial in patients with a range of solid tumors carrying FGFR2 (搜索) fusion or rearrangement mutations. Patient enrollment and dosing are proceeding at sites in South Korea, the United States, the United Kingdom and Europe. The company noted that timelines may be adjusted based on enrollment trends and FDA requirements, but it is targeting an interim analysis in 2027, with the goal of expanding the indication to multiple solid tumors with FGFR2 genetic alterations.
Unmet Need in a Rare Cancer
Cholangiocarcinoma (搜索) is a rare cancer type with a poor prognosis, and targeted treatment options after first-line therapy in the advanced or metastatic setting remain limited. FGFR2 (搜索) mutations are known to occur in approximately 10–15% of cholangiocarcinoma patients. If lirafugratinib is approved in the United States and Europe, it is expected to provide a new second-line targeted treatment option for this patient population.