Incyte recently announced that the European Commission (EC) has approved Pemazyre (pemigatinib), a selective fibroblast growth factor receptor (FGFR) kinase inhibitor, for the treatment of patients with unresectable locally advanced or metastatic cholangiocarcinoma who have relapsed or are refractory to at least one systemic therapy, have FGFR2 fusions or rearrangements, and whose disease has relapsed.
Pemazyre's active pharmaceutical ingredient, pemigatinib, is a potent, selective, orally administered small molecule inhibitor targeting FGFR isoforms 1, 2, and 3. In preclinical studies, pemigatinib has demonstrated potent and selective pharmacological activity against cancer cells with FGFR gene alterations.
The regulatory approvals of Pemazyre in the US, Japan, and the EU are based on data from the FIGHT-202 study. This study evaluated the efficacy and safety of Pemazyre in patients with previously treated locally advanced or metastatic cholangiocarcinoma. The results of this study were recently presented at the European Society for Medical Oncology (ESMO) Congress 2019.
Data showed that in patients with FGFR2 fusions or rearrangements (cohort A), with a median follow-up of 15 months, the overall response rate (ORR) of Pemazyre monotherapy was 36% (primary endpoint), and the median duration of response (DoR) was 7.49 months (secondary endpoint).
The most common treatment-acting adverse event (TEAE) during treatment in this study was ≤ grade 2 hyperphosphatemia (58.2%). Other more frequent TEAEs (all grades) observed in ≥30% of patients included alopecia, diarrhea, fatigue, dysphagia, nausea, constipation, stomatitis, dry mouth, and decreased appetite. Most of these TEAEs were ≤ grade 2. ≥ grade 3 TEAEs occurring in ≥10% of patients were hypophosphatemia.
Regarding the approval status of Pemazyre:
In April 2020, Pemazyre was the first drug approved by the US FDA for the treatment of patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or rearrangements. In March 2021, Pemazyre was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with unresectable cholangiocarcinoma carrying the FGFR2 fusion gene whose disease has progressed after chemotherapy.
Notably, Pemazyre is the first and only targeted therapy for cholangiocarcinoma in the US, Japan, and the EU. This drug works by blocking FGFR2 in tumor cells to inhibit tumor cell growth and spread. Because cholangiocarcinoma is a devastating cancer with a severely unmet medical need, Pemazyre had previously been granted Orphan Drug Designation, Breakthrough Therapy Designation, Priority Review Designation, and Accelerated Evaluation Designation.
