Pierre Fabre’s Braftovi gets EU okay for BRAF+ colorectal cancer

The EMA has approved Pierre Fabre’s Braftovi for the treatment BRAF-positive colorectal cancer, making it the first drug specifically approved for this type of cancer in the EU.

BRAF inhibitor Braftovi (encorafenib) has been cleared in a regimen alongside Merck KGaA’s EGFR-targeting antibody Erbitux (cetuximab) for second-line treatment of BRAF+ colorectal cancer patients previously treated with other systemic therapies.

Braftovi was approved for the same indication in April in the US, where it is sold by Pfizer – and was one of the key elements in the big pharma company’s $11.4bn takeover of Array Biopharma last year, particularly for its potential as a colorectal cancer treatment.

Braftovi is already approved to treat BRAF+ melanoma – a form of skin cancer – as a combination therapy with MEK inhibitor Mektovi (binimetinib), and analysts at EvaluatePharma think that colorectal cancer will account for more than $700m of the drug’s predicted global sales in 2024 of $1.2bn. Pfizer claimed approval for the colorectal cancer indication from the FDA in April.

The latest EU approval – which also covers the UK, Norway, Iceland and Liechtenstein – follows the BEACON CRC trial, which according to Pierre Fabre is the first and only phase 3 study to test a BRAF combination targeted therapy in BRAF+ colorectal cancer.

The results showed that Braftovi/Erbitux significantly improved overall survival (OS) by 40% compared to Erbitux and irinotecan-based chemotherapy, with a median OS of 9.3 months and 5.9 months, respectively.

Data from the trial also showed that the two-drug combination was as effective as a triple therapy which also included Mektovi, which meant that additional toxicity from the MEK inhibitor could be avoided without compromising patient benefits.

The trial has established Braftovi and Erbitux as a standard therapy for second-line BRAF-mutant colorectal cancer, but trials are already underway that will try to move the combination into the front-line setting.

The phase 2 ANCHOR CRC trial, which started in 2018 before the BEACON CRC results were mature, is testing triple therapy with Braftovi/Mektovi plus Erbitux or another EGFR inhibitor – Amgen’s Vectibix (panitumumab) – as a chemotherapy-free option for patients. It is due to generate results this month.

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths, with about 1.8m new  diagnoses globally, and of these 7-10% have BRAF mutations.

Novartis is also testing its BRAF/MEK combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF-positive colorectal cancer, and recently started trials of the duo alongside other Novartis drugs, including its experimental PD-1 inhibitor PDR001, in this indication.