FDA Approves Incyte’s Pemazyre as the First and Only Targeted Treatment for Rare Blood Cancer

The U.S. Food and Drug Administration approved Incyte’s Pemazyre, a selective fibroblast growth factor receptor inhibitor (FGFR), for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement, extremely rare and aggressive blood cancers.

Photo: Hervé Hoppenot, CEO of Incyte

Pemazyre (pemiganitib) is the first targeted treatment approved for use in the United States for treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. It is the second indication for Pemazyre, which received accelerated FDA approval in 2020 for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement

“The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” said Hervé Hoppenot, CEO of Incyte. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.”

A patient with an MLN with FGFR1 rearrangement may present with bone marrow involvement with a chronic myeloid malignancy (such as myeloproliferative neoplasm [MPN], myelodysplastic syndrome/MPN) or a blast phase malignancy (such as B- or 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 only. MLNs with FGFR1 rearrangement are caused by chromosomal translocations involving the FGFR1 gene, with various partner genes resulting in constitutive activation of the FGFR1 receptor tyrosine kinase, impacting cell differentiation, proliferation and survival2. Patients often relapse because existing first-line therapies sometimes fail to induce durable clinical and cytogenetic responses.

The FDA approval was based on data from the phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial that evaluated the safety and efficacy of Pemazyre in 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy or were not a candidate for allo-HSCT or other disease modifying therapies.

Study participants included patients with documented MLNs with an 8p11 translocation on conventional cytogenetics and/or an FGFR1 rearrangement on break-apart FISH testing.

In patients with chronic phase in the marrow with or without EMD (N = 18), the complete response (CR) rate was 78 percent. The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days). In patients with blast phase in the marrow with or without EMD (N = 4), two patients achieved a CR (duration: 1+ and 94 days). In patients with EMD only (N = 3), one patient achieved a CR (duration: 64+ days). For all patients (N = 28 including three patients without evidence of morphologic disease) the complete cytogenetic response rate was 79 percent.

The most common (≥ 20 percent) adverse reactions were hyperphosphatemia (74 percent), nail toxicity (62 percent), alopecia (59 percent), stomatitis (53 percent), diarrhea (50 percent), dry eye (50 percent), fatigue (44 percent), rash (35 percent), abdominal pain (35 percent), anemia (35 percent), constipation (32 percent), dry mouth (32 percent), epistaxis (29 percent), retinal pigment epithelial detachment (26 percent), extremity pain (26 percent), decreased appetite (24 percent), dry skin (24 percent), dyspepsia (24 percent), back pain (24 percent), nausea (21 percent), blurred vision (21 percent), peripheral edema (21 percent) and dizziness (21 percent).

“In patients with relapsed or refractory MLNs with FGFR1 rearrangement treated with Pemazyre in FIGHT-203, the high rate of complete response and complete cytogenetic response in patients with chronic phase disease and the high rate of complete cytogenetic response in patients with blast phase disease is clinically meaningful, especially in light of the lack of these specific responses with existing first-line treatments,” said Srdan Verstovsek, professor in the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, and principal investigator for the FIGHT-203 study.

The supplemental New Drug Application for Pemazyre for the treatment of adults with relapsed or refractory MLNs with FGFR1 rearrangement was reviewed by the FDA under Priority Review. The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists. The designation shortens the review period to six months compared to 10 months for standard review.

Author: Rare Daily Staff