FDA Approves Incyte’s Pemazyre for Rare Cancer

The U.S. Food and Drug Administration approved Incyte’s Pemazyre, a kinase inhibitor for the treatment of cholangiocarcinoma.

The accelerated approval was for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Cholangiocarcinoma is a rare cancer that forms in bile ducts, which are slender tubes that carry the digestive fluid bile from the liver to gallbladder and small intestine. At diagnosis, a majority of patients with cholangiocarcinoma have advanced disease that is no longer treatable with surgery. Until now, their only option was a combination of chemotherapy drugs. FGFR2 fusions have been found in the tumors of approximately 9 percent to 14 percent of patients with cholangiocarcinoma.

Pemazyre is a tablet that works by blocking FGFR2 in tumor cells to prevent them from growing and spreading. It is the first and only FDA-approved treatment for patients with cholangiocarcinoma that is locally advanced who have tumors that have a fusion or other rearrangement of the FGFR2 gene.

The FDA approval was based on data from the FIGHT-202 study, a multi-center, open-label, single-arm study that evaluated Pemazyre as a treatment for adults with cholangiocarcinoma. In patients harboring FGFR2 fusions or rearrangements, Pemazyre monotherapy resulted in an overall response rate of 36 percent (primary endpoint), and median duration of response of 9.1 months (secondary endpoint). Serious side effects of treatment with Pemazyre include eye problems such as dry or inflamed eyes, inflamed cornea, increased tears and a disorder of the retina; high levels of phosphate in the blood; and, for women who are pregnant, a risk of harm to the unborn baby or loss of pregnancy.

Pemazyre was approved under accelerated approval based on overall response rate and duration of response, and continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial.

Pemazyre had been granted FDA’s Orphan Drug and Breakthrough Therapy designations and was reviewed under the FDA’s Priority Review program. EU marketing authorization for pemigatinib is under review for adult patients with locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy.

The FDA is also expected to approve FoundationOne CDx as the companion diagnostic for Pemazyre. FoundationOne CDx is Foundation Medicine’s comprehensive genomic profiling assay and broad companion diagnostic platform approved for all solid tumors. If approved, this companion diagnostic would help identify patients with FGFR2 fusions or rearrangements who may be eligible for Pemazyre.

“Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,” said Ghassan Abou-Alfa of the Memorial Sloan Kettering Cancer Center. “It is encouraging to have a new targeted treatment option for patients who historically have had limited options after first-line chemotherapy or surgery, in which relapse rates remain high.”

Photo: Ghassan Abou-Alfa of the Memorial Sloan Kettering Cancer Center

Author: Rare Daily Staff