FDA Approves Incyte's Pemazyre for Rare Bile Duct Cancer

Bile Duct

The U.S. Food and Drug Administration (FDA) approved Incyte’s Pemazyre (pemigatinib) for 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 and only FDA-approved drug for the indication.

Cholangiocarcinoma is a rare cancer of the bile duct that is classified based on anatomical origin. So, intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. It is typically diagnosed late or at an advanced stage when the prognosis is poor. The incidence various from region to region, but ranges between 0.3 to 3.4 per 100,000 in North America and Europe. There are about 8,000 patients with cholangiocarcinoma in the U.S. each year.

“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.”

FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where it shows up in 10 to 16% of patients. FGFR fusions and rearrangements play a significant role in tumor cell proliferation and survival, migration and the formation of new blood vessels, called angiogenesis.

An FDA-approved companion diagnostic is used to test the cancers for the FGFR fusions. The agency also approved FoundationOne CDx as the companion diagnostic for the drug. FoundationOne CDx is Foundation Medicine’s comprehensive genomic profiling assay and companion diagnostic platform approved for all solid tumors. Foundation Medicine is a Roche company.

The drug was approved on the basis of the Phase II FIGHT-202 trial, a multi-center, open-label, single-arm study of Pemazyre for adults with cholangiocarcinoma patients with FGFR2 fusions or rearrangements (Cohort A). The trial showed the drug as a monotherapy had an overall response rate (ORR) of 36%, which was the trial’s primary endpoint, and a median duration of response (DOR) of 9.1 months, a secondary endpoint.

The trial has three cohorts. Cohort A evaluated patients with the FGFR2 fusions or rearrangements. The other two cohorts include patients with other forms of FGF or FGFR genetic changes and the third cohort is in patients with no FGF or FGFR genetic alterations.

The drug was granted Breakthrough Therapy designation for this indication, as well as Orphan Drug designation. The New Drug Application (NDA) was reviewed under the agency’s Priority Review program.

“Our research into FGFR2 fusions or rearrangements in cholangiocarcinoma and the development of Pemazyre as the first targeted treatment option demonstrates our commitment to translating scientific discovery into solutions that can positively impact patients’ lives,” said Herve Hoppenot, chief executive officer of Incyte. “We’re proud to bring Pemazyre to patients and will make this new treatment available immediately.”

One of the conditions of the accelerated approval is that Incyte will run a randomized-controlled trial after approval to show the drug improves PFS and overall survival over a comparator drug, with continued approval contingent on the results of the study.

The drug carries a risk of ocular toxicity. In the trial, 20% of patients had electrolyte disorders, alopecia (hair loss), diarrhea, nail toxicity, and fatigue.

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