US FDA grants priority review status to Pfizer's sNDA for Braftovi in combo with Erbitux to treat BRAFV600E-mutant metastatic colorectal cancer after prior therapy

Pfizer announced that the US Food and Drug Administration (FDA) has accepted and granted priority review to the company’s supplemental New Drug Application (sNDA) for Braftovi (encorafenib) in combination with Erbitux (cetuximab) (Braftovi Doublet) based on results from the phase 3 BEACON CRC trial, which evaluated the efficacy and safety of Braftovi in combination with Erbituxwith or without Mektovi (binimetinib) in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy.

As published in The New England Journal of Medicine (NEJM), results from the BEACON CRC trial showed improvements in overall survival (OS) and objective response rates (ORR) for both the Braftovi Doublet and Braftovi Triplet (Braftovi, Mektovi and Erbitux) combination, compared to Erbituxplus irinotecan-containing regimens (Control). In descriptive analyses comparing the Doublet and Triplet arms, the results showed comparable efficacy between the Doublet and Triplet in the overall population. The Braftovi Triplet and Doublet showed no unexpected toxicities.

“The FDA’s acceptance of our application for the Braftovi Doublet is highly encouraging news for patients with mCRC harboring a BRAFV600E mutation,” said Chris Boshoff, M.D., Ph.D., chief development officer, oncology, Pfizer Global Product Development. “Currently, there are no FDA-approved treatments specifically for patients with BRAF-mutant mCRC who have received prior treatment. If approved, the Braftovi Doublet would become the first targeted regimen for this patient population, who typically have a poor prognosis. We also look forward to continuing to explore this targeted Doublet regimen with or without Mektovi in earlier lines of BRAF-mutant mCRC, including in the ongoing, phase 2 ANCHOR study in previously untreated patients.”

The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2020.

On November 2, 2019, the European Medicines Agency (EMA) also started the review procedure for Pierre Fabre’s Type II variation applications based on the BEACON CRC trial.

BEACON CRC is a randomised, open-label, global trial evaluating the efficacy and safety of Braftovi, MEKTOVI and Erbituxin patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens.

The randomised portion of the BEACON CRC trial is designed to assess the efficacy and safety of Braftovi in combination with Erbituxwith or without MEKTOVI compared to Erbituxand irinotecan-based therapy. 665 patients were randomized 1:1:1 to receive the Triplet combination, the Doublet combination (Braftovi and Erbitux) or the control arm (irinotecan-based therapy and Erbitux). The study was amended to include an interim analysis of endpoints including ORR. The primary overall survival endpoint is a comparison of the Triplet combination to the control arm. Secondary endpoints address efficacy of the Doublet combination compared to the control arm, and the Triplet combination compared to the doublet therapy. Other secondary endpoints include progression-free survival, duration of response, safety and tolerability. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. The BEACON CRC trial is being conducted with support from Ono Pharmaceutical Co. Ltd., Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

Braftovi is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma and colorectal cancer. In the US, Braftovi + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. Braftovi is not indicated for treatment of patients with wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test. In Japan, the combination is approved for unresectable melanoma with a BRAF mutation.

Pfizer has exclusive rights to Braftovi and Mektovi in the US and Canada. Ono Pharmaceutical Co. Ltd. has exclusive rights to commercialize both products in Japan and South Korea, Medison has exclusive rights to commercialize both products in Israel and Pierre Fabre has exclusive rights to commercialise both products in all other countries, including Europe, Latin America and Asia (excluding Japan and South Korea).



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