August 26, 2022, Wilmington, Delaware, BUSINESS WIRE.
Incyte announced that the U.S. Food and Drug Administration (FDA) has approved pemigatinib® (pemigatinib, a selective fibroblast growth factor receptor [FGFR] inhibitor) for the treatment of adult patients with relapsed or refractory myeloid/lymphoid cancers (MLNs) with FGFR1 rearrangements. FGFR1-rearranged MLNs are extremely rare and aggressive blood cancers, affecting less than one in 100,000 people in the United States.
Patients with FGFR1-rearranged MLNs may present with chronic myeloid malignancies involving the bone marrow or blastic-stage malignancies such as B/T-cell acute lymphoblastic leukemia/lymphoma, acute myeloid leukemia, or mixed phenotype acute leukemia. Bone marrow involvement may or may not be accompanied by extramedullary disease (EMD); some patients may present with EMD alone. MLNs are caused by chromosomal translocations involving the FGFR1 gene, with different partner genes leading to persistent activation of the FGFR1 receptor tyrosine kinase, affecting cell differentiation, proliferation, and survival. Patients often relapse because existing first-line therapies fail to induce durable clinical and cytogenetic responses.
Recently, the FDA approved the drug for marketing based on safety and efficacy data from a Phase II, multicenter, open-label, single-arm study of FIGHT-203. This drug will be used to treat 28 patients with relapsed or refractory FGFR1 rearranged MLNs. Patients may have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or disease-modifying therapy, or may not be eligible for allo-HSCT or other disease-modifying therapies.
Study subjects were patients with MLNs characterized by 8p11 translocations confirmed by conventional cytogenetic testing or FGFR1 rearrangements confirmed by isolated FISH assays.
In patients in the chronic phase of myeloid blast disease with or without EMD (N=18), the complete remission (CR) rate was 78%. The median time to CR was 104 days (range 44–435 days). The median duration of CR was not reached (range 1+ to 988+ days).
In patients in the myeloblastic phase with or without EMD (N=4), 2 patients achieved CR (duration: 1+ and 94 days).
In patients with EMD only (N=3), 1 patient achieved CR.
The complete cytogenetic remission rate was 79% in all patients (N=28, including 3 patients with no evidence of morphological disease).
Common adverse reactions of pemigatinib (incidence ≥20%): Hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelium detachment (26%), limb pain (26%), decreased appetite (24%), dry skin (24%), indigestion (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%), dizziness (21%).
Pemigatinib Expert Review
“For patients with relapsed or refractory FGFR1 rearranged MLNs treated with Pemazyre in the FIGHT-203 study, the complete response rate and complete cytogenetic response rate in chronic phase patients, and the complete cytogenetic response rate in blast crisis patients, are of significant clinical importance, especially considering the lack of these specific responses in existing first-line treatments,” said Srdan Verstovsek, MD, PhD, Professor of Leukemia, Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, and Principal Investigator of the FIGHT-203 study.
Pemigatinib Approval Information
The supplemental New Drug Application (sNDA) for pemigatinib for the treatment of adults with FGFR1 rearranged relapsed or refractory MLNs has been granted Priority Review by the FDA. The FDA grants Priority Review designation to drugs that are likely to provide significant therapeutic progress in the absence of existing treatments, reducing the review period from 10 months to 6 months.
