Lyrfigtu (lirafugratinib)

A once-daily pill approved by the FDA on September 23, 2026 as Lyrfigtu for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 gene fusion or other rearrangement. It is built to block FGFR2 more selectively than the older FGFR inhibitors.

In a minority of intrahepatic cholangiocarcinomas, a piece of the FGFR2 gene is fused to an unrelated gene, and the fused protein signals the cancer cell to grow nonstop. The 2 earlier FGFR drugs still on the market block FGFR2 but also its close relatives. By their FDA labels, pemigatinib blocks FGFR1, FGFR2 and FGFR3, and touches FGFR4 only at about 100 times the concentration, while futibatinib blocks all 4. Blocking FGFR1 raises blood phosphate, and blocking FGFR4 causes diarrhea, which is why dose cuts and pauses are common on those drugs. Lirafugratinib was designed with long molecular-dynamics simulations of how the 4 receptors move, and it binds a flexible loop that only FGFR2 exposes; in lab tests it is about 250 times more selective for FGFR2 than FGFR1 and about 5,000 times more than FGFR4. It binds permanently (covalently), and it was built to keep working against several FGFR2 mutations that cause resistance to the older drugs.

In the 116-patient pivotal ReFocus cohort, the most common serious (grade 3 or higher) side effects were the on-target skin and mouth effects of blocking FGFR2: hand-foot syndrome (palmar-plantar erythrodysesthesia, painful redness and peeling on the palms and soles) in 32.8% and mouth sores (stomatitis) in 12.1%. Side effects led to a dose reduction in 75.9% of patients and a pause in 82.8%, but only 4.3% stopped the drug because of them. The drug was designed to avoid the high phosphate and diarrhea seen with the older FGFR drugs. In the safety data behind the approval, high phosphate was still reported in 21% of patients, though almost always mild, and diarrhea occurred in 22% of patients (0.9% grade 3 or 4). The FDA label warns about eye problems, including fluid under the retina (retinal pigment epithelial detachment, seen in 31%), so an eye exam with a retina scan is needed before starting, every 2 months for the first 13 months and every 4 months after that, and right away for any vision change. It also warns about high blood phosphate that can lead to calcium deposits in soft tissues, so phosphate is checked throughout treatment, and about harm to a developing baby: women who could become pregnant should use effective birth control during treatment and for 6 months after the last dose, and men with such partners for 3 months after the last dose.

An oral pill, 70mg once a day, taken continuously until the cancer grows or side effects become too much. Doses are commonly lowered or paused to manage hand-foot syndrome and mouth sores. The approved dose is 70mg once daily. Treatment requires a tumor test showing an FGFR2 fusion or other rearrangement.

Yes, Lirafugratinib (Lyrfigtu) is FDA approved (2026) for the treatment of Cholangiocarcinoma.

Yes. The FDA approved lirafugratinib, brand name Lyrfigtu, on September 23, 2026 for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 gene fusion or other rearrangement. The approved dose is 70mg by mouth once daily.

It is designed to block FGFR2 selectively, about 250 times more than FGFR1 and 5,000 times more than FGFR4 in lab tests. Pemigatinib blocks FGFR1, FGFR2 and FGFR3, and futibatinib blocks all 4 receptors. That selectivity is meant to avoid the high phosphate and diarrhea those drugs cause. In its pivotal trial 46.5% of patients responded with a median response of 11.8 months, compared with 36% and 9.1 months for pemigatinib and 42% and 9.7 months for futibatinib in their own trials, though separate single-arm trials cannot be compared directly.

Hand-foot syndrome and mouth sores, the on-target effects of blocking FGFR2. In the pivotal cohort, 32.8% had severe hand-foot syndrome and 12.1% severe mouth sores. Most patients needed a dose reduction, but only 4.3% stopped because of side effects. The FDA label also warns about eye toxicity, high blood phosphate with soft tissue mineralization, and harm to a developing baby.