FDA Approves Orphan Drug Pemigatinib for Rare Bile Duct Cancer Cholangiocarcinoma

FDA has approved pemigatinib (Pemazyre) for treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement. It is the first targeted therapy for patients with cholangiocarcinoma, a rare cancer that impacts the bile ducts.

The disease is often diagnosed at a late or advanced stage when the prognosis is poor.

Pemigatinib is an oral kinase inhibitor and has demonstrated selective pharmacologic activity against cancer cells with FGFR changes. It was approved under an accelerated approval process and continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s), according to the drugmaker, Incyte. The drug also received Orphan Drug status.

The “approval of [pemigatinib] provides an exciting new treatment option for patients and will bring hope to those who typically face a difficult diagnosis journey and poor prognosis,” said Stacie Lindsey, president of the Cholangiocarcinoma Foundation, in a statement.

Cholangiocarcinoma is a rare cancer of the bile duct. Intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver, whereas extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. FGFR2 fusion or rearrangements occurs almost exclusively in iCCA and is observed in 10-16% of patients.

“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,” noted Ghassan Abou-Alfa, MD from Memorial Sloan Kettering Cancer Center.

FGFRs plays a role in tumor cell production and survival. They also cause migration and angiogenesis (the formation of new blood vessels). FGFR fusion, rearrangements, translocations, and gene amplifications are closely correlated with the development of various cancers.

Cholangiocarcinoma incidence varies regionally and can occur in 0.3-3.4 of people per 100,000 in North America and Europe. “Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,” said Abou-Alfa.

The FDA approval evaluated data from the FIGHT-202 study, which is a multi-center, open-label, single-arm study. Monotherapy using pemigatinib resulted in an overall response rate of 36% (primary endpoint) and median of 9.1 months for the duration of response (secondary endpoint).

Pemigatinib is currently under review by the European Medicines Agency (EMA) treatment of adults with locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy.

Main risks associated with the drug include a serious of eye problems such as dry or inflamed eyes, inflamed cornea, increased tears and a disorder of the retina. Pemigatinib can also cause high blood phosphate levels and an increased risk in pregnant women of harm to the fetus or miscarriages.

The most common side effects of pemigatinib include hair loss, diarrhea, nails separate from the bed or poor formation of the nail, feeling tired, change in sense of taste, nausea, constipation, mouth sores, dry eyes, dry mouth, decrease in appetite, vomiting, joint pain, abdominal pain, low phosphate in blood, back pain, and dry skin.