Pierre Fabre today announced that the European Commission (EC) has approved encorafenib in combination with cetuximab for the treatment of adult patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) who have received prior systemic therapy.

This approval is based on data from the Phase 3 BEACON CRC trial.

The EC decision is applicable to all 27 EU member states plus Iceland, Liechtenstein, Norway and the United Kingdom.
 
“This approval is truly great news and much needed for patients with BRAF V600E-mutant mCRC and for physicians treating this devastating cancer, as until now, there has been no EC-approved therapies specifically indicated for this high-medical-need population,” said Josep Tabernero, MD, PhD, BEACON CRC trial lead investigator and director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain.

“The new encorafenib and cetuximab combination regimen will now change the way we treat these patients, with the possibility of delaying disease progression and prolonging their lives.”
 
The EC decision, which follows the positive opinion by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on 30 April 2020, is based on available results from the pivotal Phase 3 BEACON CRC trial, the first and only randomised Phase 3 trial designed to test a BRAF combination targeted therapy in BRAF V600E-mutant mCRC. 

The data showed that encorafenib in combination with cetuximab significantly improved overall survival (OS) in patients with BRAF V600E-mutant mCRC (median 9.3 months vs 5.9 months; hazard ratio: 0.61; 95% confidence interval: 0.48–0.77; p<0.0001) and reduced the risk of death by 39%, compared with the cetuximab plus irinotecan-containing regimen (control) arm.

Furthermore, the data also reported an improved objective response rate (ORR; 20% vs 2%; p<0.0001; per assessment by blinded independent central review [BICR]), compared with the control arm. encorafenib plus cetuximab demonstrated a well-tolerated safety profile with no unexpected toxicities in the trial.

The most common adverse drug reactions (>25%), observed in the BEACON CRC trial, were fatigue, nausea, diarrhoea, dermatitis acneiform, abdominal pain, arthralgia/musculoskeletal pain, decreased appetite, rash and vomiting.
 
"We are extremely pleased that patients will now have access, for the very first time, to a targeted therapy specifically for BRAF V600E-mutant mCRC,” said Jean-Luc Lowinski, CEO of Pierre Fabre Medical Care Business Unit.

“Today’s approval is a testament to our long-term commitment to advancing care for patients living with difficult-to-treat cancers and to delivering precision medicine. We will now work tirelessly to bring this new treatment option to patients in Europe, as quickly as possible.”
 
BRAF mutations are estimated to occur in approximately 8–12% of patients with mCRC, and V600E is the most common mutation.

Patients with mCRC who have BRAF V600E-mutant tumours generally have a poor prognosis representing a high unmet medical need.

Currently, there are no other approved targeted treatments in Europe specifically indicated for this patient population.
 
Important safety information and recommendations for the use of encorafenib in combination with cetuximab will be detailed in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages.

The full SmPC will be found at www.ema.europa.eu.

On 8 April 2020, Pierre Fabre’s partner Pfizer, which has exclusive rights to encorafenib in the USA and Canada, announced that encorafenib, in combination with cetuximab, was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with mCRC with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

Additional submissions of the BEACON data to health authorities around the world are planned.

Source: Pierre Fabre