FDA approves Elevar Therapeutics' Lyrfigtu for bile duct cancer with FGFR2 alterations

On September 23, 2026, the FDA approved Elevar Therapeutics' oral drug Lyrfigtu (lirafugratinib) for adults with previously treated, advanced cholangiocarcinoma harboring FGFR2 alterations. The approval is backed by the Phase I/II ReFocus trial, where Lyrfigtu achieved a 46% objective response rate and a median progression-free survival of 11.3 months. Lyrfigtu's selective, covalent-binding mechanism targets FGFR2 while minimizing toxicities, offering a vital new second-line option.

FDA approval and US availability

• ▪The FDA granted priority review designation to lirafugratinib in March 2026, a status reserved for drugs that could significantly improve the safety or effectiveness of treating serious conditions.
• ▪Elevar Therapeutics, a majority-owned subsidiary of HLB Co., Ltd., expects lirafugratinib to be available to patients in the United States by the end of 2026.
• ▪The FDA approved the oral FGFR2 inhibitor lirafugratinib, marketed as Lyrfigtu, on September 23, 2026, for adults with previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma with FGFR2 fusion or other rearrangements.

ReFocus trial efficacy results

• ▪Lirafugratinib demonstrated a median duration of response of 11.8 months in the Phase I/II ReFocus trial, with a safety profile manageable through dose adjustments.
• ▪In the Phase I/II ReFocus trial of 116 patients with previously treated FGFR2-positive cholangiocarcinoma and no prior FGFR inhibitor exposure, lirafugratinib demonstrated an objective response rate of 46%.
• ▪In the Phase I/II ReFocus trial, patients treated with lirafugratinib achieved a median progression-free survival of 11.3 months and a 12-month progression-free survival rate of 49.2%.
• ▪The Phase I/II ReFocus trial showed a median overall survival of 22.8 months, a 12-month overall survival rate of 74.6%, and a disease control rate of 96.5% for patients treated with lirafugratinib.
• ▪Dr. Robin Kate Kelley of the University of California, San Francisco noted that patients in the ReFocus trial achieved robust tumor shrinkage and regained meaningful quality of life.

Prescribing warnings and side effects

• ▪The prescribing information for lirafugratinib includes warnings for ocular toxicity, including retinal pigment epithelial detachment which occurred in 31% of 385 patients, dry eye, and corneal toxicity.
• ▪Lirafugratinib prescribing warnings also cover hyperphosphatemia, which occurred in 21% of patients with a median onset of 15 days, soft tissue mineralization, and embryo-fetal toxicity.

Mechanism of action

• ▪Lirafugratinib is an oral small molecule inhibitor designed to selectively target FGFR2 while minimizing off-isoform toxicities associated with earlier pan-FGFR inhibitors.
• ▪Dr. Lipika Goyal of Stanford Cancer Center stated that lirafugratinib's irreversible, covalent-binding mechanism enables potent and sustained inhibition of FGFR2, including resistance mutations from earlier FGFR inhibitors.

Lirafugratinib licensing and development

• ▪Elevar Therapeutics is evaluating lirafugratinib in clinical trials for patients with other previously treated, advanced or metastatic solid tumors harboring FGFR2 fusions or rearrangements.
• ▪Elevar Therapeutics holds an exclusive license to lirafugratinib from Relay Therapeutics, Inc. for worldwide commercialization.

Debatable claims

• ▪Lyrfigtu's clinical benefits outweigh its severe ocular and systemic risks
• ▪The FDA is justified in approving Lyrfigtu based on Phase I/II trial data
• ▪Lyrfigtu represents a significant advancement in bile duct cancer treatment
• ▪Clinicians should mandate molecular testing at diagnosis for all bile duct cancer patients