The U.S. Food and Drug Administration on Sept. 23 approved lirafugratinib, a once-daily pill sold as Lyrfigtu, for adults with advanced bile duct cancer whose tumors carry an FGFR2 gene fusion or other rearrangement and who have already received treatment, OncLive reported.
Bile duct cancer, or cholangiocarcinoma, is rare, with about 8,000 new U.S. diagnoses each year, according to the American Cancer Society. It is often found late, when surgery is no longer possible. FGFR2 fusions or rearrangements appear in roughly 10% to 15% of cancers that start in the bile ducts inside the liver, Oncology Nursing News reported, so the approval applies to a small but seriously ill group.
The drug's maker, Elevar Therapeutics, said it expects the medicine to be available in the U.S. by the fourth quarter of 2026.
Who Qualifies and How the Drug Works
The approval covers adults whose cholangiocarcinoma cannot be removed surgically or has spread, whose tumors test positive for an FGFR2 gene fusion or other rearrangement, and who have received prior treatment. FGFR2 is a growth-signaling protein. When the gene is abnormally fused with another gene, it can stay switched on and drive tumor growth.
Lirafugratinib blocks that signal. Unlike earlier drugs that act on the whole FGFR family, it is designed to target FGFR2 selectively and binds to it permanently. The recommended dose is 70 milligrams by mouth once a day until the cancer progresses or side effects become unacceptable.
Patients learn whether they qualify through genomic testing of the tumor, which makes testing at diagnosis important. "The results also reinforce the importance of molecular testing at diagnosis so that patients can be matched to therapies most likely to benefit them," said Dr. Alison Schram, a gynecologic medical oncologist at Memorial Sloan Kettering Cancer Center, in a statement released by the company.
The Trial Results and Their Limits
The approval was based on REFOCUS, an open-label, single-arm trial of 116 patients who had received prior chemotherapy or chemoimmunotherapy but had never taken an FGFR inhibitor. Tumors shrank enough to count as a response in 46% of patients, and responses lasted a median of 11.8 months, according to CURE.
The company also reported a median progression-free survival of 11.3 months, with 49.2% of patients living without cancer progression at one year, according to Elevar's announcement.
Those results come with important limits. The trial had no comparison group, so it cannot show whether patients lived longer than they would have with other treatment. It measured tumor shrinkage, not overall survival. It also excluded people who had already taken an FGFR inhibitor, so the data do not show how well the drug works after earlier FGFR-targeted drugs stop working.
Dr. Lipika Goyal of the Stanford Cancer Center, the study's lead author, said in the company's release that the drug can inhibit FGFR2, "including many resistance mutations that can emerge with earlier FGFR inhibitors." That claim has not been tested in a head-to-head trial. The expert comments in this story were provided through Elevar's announcement.
The FDA granted the application priority review, and the drug received breakthrough therapy and orphan drug designations, CancerNetwork reported.
Side Effects Patients Should Expect
Eye problems are the main safety concern, and they are common. Among 385 patients who received the drug across studies, 31% developed retinal pigment epithelial detachment, a fluid buildup under the retina that can blur vision, and 38% had dry eye, according to the prescribing information summarized by Elevar. The label calls for a full eye exam, including an imaging scan of the retina, before treatment starts, then every two months for the first 13 months and every four months after that.
The drug can also raise blood phosphate levels, which occurred in 21% of patients and can lead to calcium deposits in soft tissue, so phosphate is monitored throughout treatment. It can harm a developing pregnancy. Women are advised to use effective contraception during treatment and for six months afterward, and men with female partners who could become pregnant for three months afterward.
Serious side effects occurred in 32% of patients, most often infection, pneumonia, fatigue, and bleeding, and one patient died of bleeding. Common side effects include nail changes, hand-foot skin reactions, mouth sores, hair loss, dry eye, dry mouth, fatigue, and taste changes.
Patients should report any new blurred vision promptly, since the label calls for urgent eye evaluation. Fever, heavy bleeding, or signs of serious infection need immediate medical attention.
Cost, Access and Next Steps
Elevar has not announced a price. Families can ask the oncology team about insurance prior authorization, specialty pharmacy options, and manufacturer assistance programs once the drug launches.
Patients taking another FGFR inhibitor should not switch without talking to their oncologist. Those not yet tested for FGFR2 changes can ask whether tumor genomic testing has been done. Elevar has also applied for approval in Europe and is studying the drug in other FGFR2-altered cancers.
Lirafugratinib offers a new targeted option for a small group of previously treated patients with FGFR2-driven bile duct cancer, with nearly half seeing tumor shrinkage. Frequent eye checks are part of treatment, and a survival benefit has not been shown in a comparison trial.
Key Questions Answered
What did the FDA approve?
Lirafugratinib (Lyrfigtu), a once-daily pill for adults with previously treated, advanced bile duct cancer that has an FGFR2 gene fusion or other rearrangement.
How well did it work in the trial?
In a single-arm trial of 116 patients, 46% had tumor shrinkage, and responses lasted a median of 11.8 months.
What are the main side effects?
Eye problems, including fluid buildup under the retina and dry eye, high phosphate levels, nail and skin changes, mouth sores and fatigue. Regular eye exams are required.
How do patients know if they qualify?
Through genomic testing of the tumor to look for an FGFR2 fusion or rearrangement. Patients can ask their oncologist whether this testing has been done.
When will the drug be available?
Elevar Therapeutics said it expects Lyrfigtu to be available in the U.S. by the fourth quarter of 2026. A price has not been announced.
Published by Medicaldaily.com
