CASTRES, France--(BUSINESS WIRE)--Pierre Fabre today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of the indication of BRAFTOVI® (encorafenib) in combination with cetuximab (marketed as Erbitux®) for the treatment of adult patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) who have received prior systemic therapy. This opinion is based on data from the Phase 3 BEACON CRC trial.1,2 The CHMP recommendation will now be endorsed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). This decision will be applicable to all 27 EU member states plus Iceland, Liechtenstein, Norway and the United Kingdom.3
“The positive CHMP opinion is an important milestone for patients with BRAF-mutant metastatic colorectal cancer who generally have a poor prognosis with current approved therapies,” said Jean-Luc Lowinski, CEO of the Medical Care Business Unit. “We are delighted to be closer to offering a new treatment option for these individuals. If approved, this will be the first targeted regimen for the treatment of BRAFV600E-mutant mCRC that has the potential to significantly improve clinical outcomes in this patient population.”
The CHMP positive opinion is based on available results from the Phase 3 BEACON CRC trial. The data, presented by Professor Scott Kopetz at the American Society of Clinical Oncology Gastrointestinal meeting in January 2020, showed that BRAFTOVI in combination with cetuximab significantly improved overall survival (OS) in patients with BRAFV600E-mutant mCRC (median 9.3 months vs 5.9 months) and reduced the risk of death by 40%, compared with the cetuximab plus irinotecan-containing regimen (control) arm. Furthermore, the combination 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. BRAFTOVI plus cetuximab demonstrated a well-tolerated safety profile with no unexpected toxicities in the trial. In the BEACON CRC trial, the most common any-grade adverse events (≥20%) were nausea, diarrhoea, fatigue, acneiform dermatitis, decreased appetite, abdominal pain, asthenia and vomiting.2
On 8 April 2020, Pierre Fabre’s partner Pfizer, which has exclusive rights to BRAFTOVI in the USA and Canada, announced that BRAFTOVI, in combination with cetuximab, was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with mCRC with a BRAFV600E mutation, as detected by an FDA-approved test, after prior therapy.4 In the US prescribing information for BRAFTOVI, the most common any-grade adverse drug reactions (≥25%) reported for patients treated with BRAFTOVI in combination with cetuximab were fatigue, nausea, diarrhoea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia and rash.5 The Summary of Product Characteristics (SmPC) for BRAFTOVI in combination with cetuximab for the treatment of adult patients with BRAFV600E-mutant mCRC will include the full list of the adverse drug reactions, which will be published by the EMA following the EC’s approval of this indication.
BRAFTOVI is not currently approved in any other country outside of the USA for treatment of patients with BRAFV600E-mutant mCRC.4 Additional submissions of the BEACON data to health authorities around the world are ongoing.
About Colorectal Cancer
Worldwide, colorectal cancer (CRC) is the third most common type of cancer in men and the second most common in women, with approximately 1.8 million new diagnoses in 2018. Globally in 2018, approximately 881,000 deaths were attributed to CRC.6 Every year more than 450,000 people in Europe are diagnosed with CRC and approximately 230,000 will die of their disease.7 BRAF mutations are estimated to occur in approximately 8–12% of patients with mCRC and represent a poor prognosis for these patients.8–16 The V600E mutation is the most common BRAF mutation and the risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF.7,17,18
About BEACON CRC
BEACON CRC is a randomised, open-label, global trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) ± binimetinib in combination with cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF combination targeted therapy in BRAFV600E-mutant mCRC. A total of 665 patients were randomised 1:1:1 to one of the following treatment arms:
- BRAFTOVI 300 mg orally once daily in combination with cetuximab (BRAFTOVI/cetuximab arm)
- BRAFTOVI 300 mg orally once daily in combination with cetuximab and binimetinib
- Irinotecan with cetuximab or FOLFIRI with cetuximab (control arm)
The study was amended to include an interim analysis of endpoints, including ORR. The primary OS endpoint is a comparison of BRAFTOVI+binimetinib in combination with cetuximab with the control arm. Secondary endpoints address the efficacy (OS) of BRAFTOVI in combination with cetuximab, compared with the control arm and compared with BRAFTOVI+binimetinib in combination with cetuximab. Other secondary endpoints include progression-free survival, duration of response, safety and tolerability.
The trial was conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. The BEACON CRC trial was conducted with support from Ono Pharmaceutical Co. Ltd., Pierre Fabre, Pfizer and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).
About BRAFTOVI® (encorafenib)
BRAFTOVI (encorafenib) is an oral small-molecule BRAF kinase inhibitor that targets a key enzyme in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, colorectal cancer and others.
On 20 September 2018, the EC granted marketing authorisations for BRAFTOVI and MEKTOVI to be used in combination for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation.19,20 The EC decision is applicable to all 27 EU member states as well as Iceland, Liechtenstein, Norway and the United Kingdom. BRAFTOVI and MEKTOVI have also received regulatory approvals in the USA, Australia, Japan, Argentina and Switzerland. On 27 June 2018, the combination of BRAFTOVI and MEKTOVI was approved by the FDA for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.5,21 BRAFTOVI and MEKTOVI are not indicated for treatment of patients with wild-type BRAF melanoma.
On 8 April 2020, the US FDA granted the approval for BRAFTOVI, in combination with cetuximab, for the treatment of adult patients with mCRC with a BRAFV600E mutation, as detected by an FDA-approved test, after prior therapy.4 The use of BRAFTOVI in combination with cetuximab for the treatment of patients with BRAFV600E-mutant mCRC is not approved outside the U.S.
Pfizer has exclusive rights to BRAFTOVI in the USA and Canada. Pfizer has granted Ono Pharmaceutical Co. Ltd. exclusive rights to commercialise BRAFTOVI in Japan and South Korea; Medison exclusive rights to commercialise both products in Israel; and Pierre Fabre exclusive rights to commercialise BRAFTOVI in all other countries in Africa, Asia (excluding Japan and South Korea), Europe, and Latin America.
About Pierre Fabre
Pierre Fabre is the second largest dermo-cosmetics laboratory in the world, the second largest private French pharmaceutical group, and the market leader in France for products sold over the counter in pharmacies. Its portfolio includes several global brands and franchises, including Eau Thermale Avène, Klorane, Ducray, René Furterer, A-Derma, Galénic, Elancyl, Naturactive, Pierre Fabre Health Care, Pierre Fabre Oral Care, Pierre Fabre Dermatologie and Pierre Fabre Oncologie.
In 2019, Pierre Fabre generated 2.4 billion euros in revenues, of which two-thirds originated from its international business.
Pierre Fabre, which has always been headquartered in the South-West of France, employs approximately 10,500 people worldwide, owns subsidiaries and offices in 45 countries and enjoys distribution agreements in over 130 countries.
Pierre Fabre is 86%-owned by the Pierre Fabre Foundation, a government-recognised public-interest foundation, and secondarily by its own employees through an international employee stock ownership plan.
In 2019, Ecocert Environment assessed the Group’s corporate social and environmental responsibility approach according to the ISO 26000 standard on sustainable development and awarded it the ECOCERT 26000 “Excellence” level.
 European Medicines Agency. CHMP Opinion: BRAFTOVI® (encorafenib). Available at: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/braftovi-0. Accessed April 2020.
 Kopetz S, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer. N Engl J Med. 2019;3811632-43.
 European Medicines Agency. Brexit: the United Kingdom’s Withdrawal from the European Union. Available at: https://www.ema.europa.eu/en/about-us/brexit-united-kingdoms-withdrawal-european-union#transition-period-section. Accessed April 2020.
 Pfizer. U.S. FDA Approves Braftovi® (encorafenib) in Combination with Cetuximab for the Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer (CRC) After Prior Therapy. Available at https://investors.pfizer.com/investor-news/press-release-details/2020/US-FDA-Approves-BRAFTOVI-Encorafenib-in-Combination-with-Cetuximab-for-the-Treatment-of-BRAFV600E-Mutant-Metastatic-Colorectal-Cancer-CRC-After-Prior-Therapy/default.aspx. Accessed April 2020.
 Pfizer. BRAFTOVI® (encorafenib) US Prescribing Information 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/210496s006lbl.pdf. Accessed April 2020.
 The Global Cancer Observatory, 2018. International Agency for Research on Cancer, World Health Organization. Available at: https://gco.iarc.fr/today/online-analysis-multi-bars. Accessed April 2020.
 EuropaColon. Colorectal Cancer in Europe: A Framework for Improving Outcomes for Patients. Available at: https://webgate.ec.europa.eu/chafea_pdb/assets/files/pdb/20124301/20124301_d04-00_en_ps_ecwhitepaper.pdf. Accessed April 2020.
 Maughan TS, et al. Lancet. 2011;377:2103–14.
 Souglakos J, et al. Br J Cancer. 2009;101:465–72.
 Richman SD, et al. J Clin Oncol. 2009;27:5931–7.
 Tran B, et al. Cancer. 2011;117:4623–32.
 Yokota T, et al. Br J Cancer. 2011;104:856–62.
 Tie J, et al. Int J Cancer. 2011;128:2075–84.
 Loupakis F, et al. Br J Cancer. 2009;101:715–21.
 Tviet KM, et al. J Clin Oncol. 2012;30:1755–62.
 Vecchione L, et al. Cell. 2016;165:317–30.
 Sclafani F, et al. Crit Rev Oncol Hematol. 2013;87:55–68.
 Safaee Ardekani G, et al. PLoS One. 2012;7:e47054.
 European Medicines Agency. BRAFTOVI® (encorafenib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/braftovi-epar-product-information_en.pdf. Accessed April 2020.
 European Medicines Agency. MEKTOVI® (binimetinib) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/documents/product-information/mektovi-epar-product-information_en.pdf. Accessed April 2020.
 Array BioPharma. MEKTOVI® (binimetinib) US Prescribing Information 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210498s001lbl.pdf. Accessed April 2020.