HLB announced that its U.S. subsidiary, Elevar Therapeutics, has submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for lirafugratinib. The drug is intended as a second-line treatment for advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. The submission was made on Monday.
The application is based on results from the global Phase 1/2 ReFocus clinical trial. Lirafugratinib showed promising results in patients with FGFR2 fusion-positive advanced or metastatic cholangiocarcinoma (CCA) who had previously received at least one systemic therapy. The drug achieved a 46.5% objective response rate (ORR), the primary endpoint, as assessed by an Independent Review Committee (IRC).
Key secondary endpoints were also encouraging. The median duration of response (mDOR) was 11.8 months, while median progression-free survival (mPFS) reached 11.3 months. Notably, the median overall survival (mOS) extended to 22.8 months.
Lirafugratinib sets itself apart as an irreversible inhibitor that specifically targets FGFR2. This contrasts with existing non-selective FGFR inhibitors that broadly affect FGFR1, 3, and 4. The drug’s high selectivity resulted in lower incidence rates of common FGFR inhibitor side effects, with hyperphosphatemia at 20.7% and diarrhea at 21.6%.
FGFR2, or fibroblast growth factor receptor 2, is crucial in cell growth and division. When the FGFR2 gene experiences abnormalities like fusions or rearrangements, it can lead to persistent abnormal signaling, potentially driving cancer cell growth. This makes it a key therapeutic target in cholangiocarcinoma.
Lirafugratinib has garnered significant recognition from the U.S. Food and Drug Administration (FDA). It received Orphan Drug Designation (ODD) in 2022 and Breakthrough Therapy Designation (BTD) in 2023. Elevate submitted a new drug application (NDA) to the FDA in January, which has been granted priority review. The review deadline under the Prescription Drug User Fee Act (PDUFA) is set for the 25th of this month.
Elevate is also conducting a global Phase 2 trial called ReFocus202. This study aims to evaluate lirafugratinib’s efficacy in various solid tumors with FGFR2 fusion or rearrangement, regardless of cancer type.
Patient enrollment and treatment are currently underway at clinical sites across the globe, including in the U.S., UK, EU, and South Korea. While the timeline may shift based on enrollment progress and FDA requirements, the company is targeting an interim analysis in 2027.
These efforts are part of Elevar’s broader strategy to expand lirafugratinib’s therapeutic reach beyond cholangiocarcinoma to various solid tumors harboring FGFR2 gene mutations.
Kim Dong-geun, Chief Executive Officer (CEO) of Elevar Therapeutics, expressed optimism about the drug’s potential. Lirafugratinib has demonstrated clinically meaningful therapeutic effects and a favorable safety profile, consistent with its high FGFR2 selectivity and sustained inhibition mechanism, Kim stated. Through its cancer-agnostic clinical trials, it aims to explore lirafugratinib’s therapeutic potential across a spectrum of solid tumors.