u200cFDA批准佩米替尼(pemigatinib)作为首个治疗FGFR1重排髓系/淋巴系肿瘤的靶向治疗药物

‌FDA approves pemigatinib as the first targeted therapy for the treatment of FGFR1-rearranged myeloid/lymphoid tumors

‌August 26, 2022‌ Wilmington, Del., Business Wire.

Incyte Corporation announced that the U.S. Food and Drug Administration (FDA) has approved pemigatinib, a selective fibroblast growth factor receptor [FGFR] inhibitor, for the treatment of adult patients with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangements. FGFR1-rearranged MLNs are extremely rare and aggressive blood cancers that may affect less than 1 in 100,000 people in the United States.

Patients with MLNs with FGFR1 rearrangements may present with chronic myeloid malignancies or blast-stage malignancies with bone marrow involvement (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 associated with extramedullary disease (EMD); some patients may present with EMD alone. MLNs are caused by chromosomal translocations involving the FGFR1 gene. Different partner genes lead to sustained activation of FGFR1 receptor tyrosine kinase, affecting cell differentiation, proliferation, and survival. Patients often relapse due to failure of existing first-line therapies to induce durable clinical and cytogenetic responses.

Recently, the FDA approved its Phase II FIGHT-203 for marketing based on the multi-center, open-label, single-arm safety and efficacy study data. The drug will be available for clinical treatment of 28 patients with relapsed or refractory FGFR1-rearranged MLNs. Patients may relapse after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) or disease-modifying therapy, or may be ineligible for allo-HSCT and other disease-modifying therapies.

Patients with MLNs with characteristics such as FGFR1 rearrangement, which have been confirmed to have 8p11 translocations through traditional cytogenetic testing or isolated FISH testing, were selected as research subjects.

Among patients in the chronic phase of bone marrow with or without EMD (N=18), the complete response (CR) rate was 78%. Median time to CR was 104 days (range 44-435 days). Median CR duration was not reached (range 1+ to 988+ days).

Among patients in the bone marrow blast stage with or without EMD (N=4), 2 patients achieved CR (duration: 1+ and 94 days).

Among patients with EMD only (N=3), 1 patient achieved CR).

The complete cytogenetic response rate for all patients (N=28, including 3 patients without morphological evidence of disease) was 79%.

Pemigatinib (pemigatinib) common adverse reactions (incidence ≥20%)‌:

Hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye syndrome (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia Blood (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), limb pain (26%), loss of 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 MLN treated with Pemazyre in the FIGHT-203 study, the complete response and complete cytogenetic response rates in patients in the chronic phase and the complete cytogenetic response rate in the blast phase patients have important clinical implications, especially given the lack of these specific responses with existing first-line treatments,” said MD, University of Texas said Srdan Verstovsek, MD, PhD, professor in the Department of Leukemia in the Division of Cancer Medicine at MD Anderson Cancer Center and principal investigator of the FIGHT-203 study.

‌Pemigatinib Approval Information‌

The supplemental New Drug Application (sNDA) of pemigatinib for the treatment of adults with FGFR1 rearranged relapsed or refractory MLNs has received priority review from the FDA. The FDA grants priority review status to drugs that may provide significant therapeutic advances in the absence of existing treatments, shortening the review period from 10 months for standard review to 6 months.