U.S. FDA Accepts and Grants Priority Review to sNDA for BRAFTOVI® (Encorafenib) in Combination with ERBITUX® (Cetuximab) for BRAF V600E-Mutant Metastatic Colorectal Cancer After Prior Therapy
Dec 26, 2019 10:22
CST Updated
10:22
Pfizer
Pharmaceutical R&D Developer
FDA
U.S. Food and Drug Administration
December 26, 2019 /Bio ValleyBIOON/ --Pfizer(Pfizer) recently announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) and granted it Priority Review. The sNDA seeks approval for the combination regimen of Braftovi (encorafenib) and Erbitux (cetuximab) (the Braftovi two-drug regimen) for the treatment of patients with BRAF V600E mutation-positive metastatic colorectal cancer (mCRC) whose disease has progressed following prior therapy.FDAThe Prescription Drug User Fee Act (PDUFA) target date for this sNDA has been set for April 2020.
This sNDA is based on the results of the Phase III BEACON CRC trial. The study was conducted in patients with advanced BRAF V600E–mutant metastatic colorectal cancer (mCRC) who had experienced disease progression after prior treatment with one or two therapies, and it evaluated the efficacy and safety of the Braftovi dual-drug regimen and the Braftovi triple-drug regimen (Braftovi + Erbitux + Mektovi) versus the combination of Erbitux and an irinotecan-containing regimen (control).
The results showed that, compared with the control group, both the Braftovi two-drug regimen group and the three-drug regimen group demonstrated improvements in overall survival (OS) and objective response rate (ORR). Descriptive analysis indicated that the efficacy of the two-drug and three-drug regimens was comparable in the overall study population. No unexpected toxicities were observed with either the two-drug or the three-drug regimen.
Pfizer Global Product DevelopmentTumorChris Boshoff, M.D., Chief Development Officer, stated, “The FDA’s acceptance of our application for the two-drug Braftovi regimen is very encouraging news for patients with metastatic colorectal cancer (mCRC) harboring BRAF V600E mutations. Currently, there is noFDAThe approved treatment is specifically indicated for patients with BRAF-mutant metastatic colorectal cancer (mCRC) who have previously received therapy. These patients typically have a poor prognosis, and if approved, the Braftovi two-drug regimen would become the first targeted therapy for this patient population. We also look forward to continuing to explore this targeted two-drug regimen, with or without Mektovi, for earlier-line treatment of BRAF-mutant mCRC, including in the ongoing Phase II ANCHOR study evaluating previously untreated patients with BRAF-mutant mCRC.
On November 2 this year, the European Medicines Agency (EMA) also initiated a review procedure to assess the Class II variation application submitted by the French pharmaceutical company Pierre Fabre Group for the two-drug regimen of Braftovi in treating patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).
The active pharmaceutical ingredient of Braftovi, binimetinib, is an oral small-molecule BRAF inhibitor, while the active pharmaceutical ingredient of Mektovi, encorafenib, is an oral small-molecule MEK inhibitor. MEK and BRAF are two key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Studies have shown that this pathway regulates various critical cellular activities, including cell proliferation, differentiation, survival, and angiogenesis. In many cancers, such asMelanoma, colorectal cancer and thyroid cancer, proteins in this signaling pathway have been confirmed to be abnormally activated.
In the United States, the Braftovi + Mektovi combination has been approved for unresectable or metastatic melanoma with BRAF V600E or BRAF V600K mutations. Braftovi is not suitable for treating wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma harboring BRAF V600 mutations. In Japan, the combination is approved for unresectableMelanoma。
Braftovi and Mektovi were discovered and developed by Array BioPharma. In June this year, Pfizer acquired Array BioPharma for $11.4 billion. Currently, Pfizer holds exclusive rights to these two drugs in the United States and Canada.Ono Pharmaceutical has been licensed exclusive rights to two drugs in Japan and South Korea, Medison has been licensed exclusive rights to two drugs in Israel, and Pierre Fabre Group has been licensed exclusive rights to two drugs in all other countries, including Europe, Latin America, and Asia (excluding Japan and South Korea). (Bioon.com)