FDA approves Lyrfigtu (lirafugratinib) for previously treated FGFR2-positive cholangiocarcinoma after a 46% response rate and 11.8-month median response duration.
Written By: Siddhi Bhadekar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Lyrfigtu (lirafugratinib) for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma (CCA) harboring a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement. Elevar Therapeutics expects the drug to become available to U.S. patients in the fourth quarter of 2026.
CCA, also known as bile duct cancer, is a rare malignancy, with about 8,000 new cases diagnosed annually in the United States, according to the American Cancer Society. FGFR2 alterations occur in a subset of patients and provide a target for precision treatment.
Selective FGFR2 Inhibition Targets Resistance
Lirafugratinib, also known as RLY-4008, is an oral small-molecule inhibitor that selectively targets FGFR2, one of four receptor tyrosine kinases in the FGFR family. Its irreversible covalent binding enables sustained FGFR2 inhibition, including activity against several resistance mutations that can emerge following earlier FGFR inhibitor treatment.
The selective approach distinguishes lirafugratinib from earlier pan-FGFR inhibitors, which inhibit multiple FGFR isoforms and can cause off-target toxicities.
REFOCUS Trial Demonstrated Durable Responses
The FDA based its approval on the Phase 1/2 REFOCUS trial (NCT04526106), a multicenter, open-label, single-arm study involving 116 patients with unresectable or metastatic CCA. Participants had received prior chemotherapy or chemoimmunotherapy and had not received an FGFR inhibitor.
Patients received lirafugratinib 70 mg once daily until disease progression or unacceptable toxicity.
Independent review committee assessment using RECIST v1.1 showed a 46% objective response rate (95% CI, 36%-55%) and a median duration of response of 11.8 months (95% CI, 7.5-13.0).
Median progression-free survival was 11.3 months, with a 12-month progression-free survival rate of 49.2%, according to Elevar.
Ocular Toxicity Requires Monitoring
The FDA prescribing information includes warnings for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.
Retinal pigment epithelial detachment (RPED) occurred in 31% of 385 patients treated with Lyrfigtu, including Grade 3 events in 1.8%. Blurred vision occurred in 18%, while dry eye and corneal toxicity or keratitis occurred in 38% and 11%, respectively.
The prescribing information recommends comprehensive ophthalmologic examination, including optical coherence tomography of the macula, before treatment, every two months during the first 13 months and every four months thereafter. Serum phosphate should also be monitored throughout treatment because hyperphosphatemia occurred in 21% of patients.
Executive and Expert Perspectives
Dong-Gun Kim, CEO of Elevar Therapeutics, said the approval provides a new second-line treatment option for patients with CCA and that the company is focused on making Lyrfigtu available to U.S. patients as quickly as possible.
Lipika Goyal, M.D., lead author of the REFOCUS study, highlighted lirafugratinib’s irreversible, selective FGFR2 inhibition, noting its potential to maintain activity against resistance mutations that can emerge with earlier FGFR inhibitors while limiting off-target FGFR effects.
Regulatory Review and Next Development Steps
The FDA granted lirafugratinib priority review, along with breakthrough therapy and orphan drug designations. The application also underwent review through the FDA’s Real-Time Oncology Review pilot and Assessment Aid programs.
Elevar is continuing clinical development of lirafugratinib in other FGFR2-altered solid tumors. Any future indications will require separate regulatory review and approval.
Reference
Elevar Therapeutics Announces FDA Approval of Lyrfigtu (Lirafugratinib) as Second-line Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement Treatment Option, Elevar Therapeutics, 23 September 2026
FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma, FDA, 23 September 2026
REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors, ClinicalTrials.gov ID NCT04526106
About the Writer
Siddhi Rajendra Bhadekar (Linkedin) is an M.Pharm professional with expertise in medical and scientific writing, literature review, publication writing, and evidence synthesis, supported by four peer-reviewed publications.
She brings working knowledge of ICH-GCP, MedDRA, pharmacovigilance, ADR/AE reporting, clinical data management, and regulatory documentation.
With experience across pharmaceutical R&D, Quality Control, and Quality Assurance, she combines scientific research skills with strong attention to accuracy and detail.
Her background in manuscript development, publication planning, and scientific communication enables her to translate complex healthcare information into clear, reliable content.