Scottish Medicines Consortium (SMC) publishes its acceptance of the first and only targeted combination therapy, for use in Scotland for adults with BRAFV600E mutation-positive metastatic colorectal cancer, who have had previous systemic treatment

Scottish Medicines Consortium (SMC) publishes its acceptance of the first and only targeted combination therapy, for use in Scotland for adults with BRAF^V600E mutation-positive metastatic colorectal cancer, who have had previous systemic treatment

Reading, United Kingdom, (Monday 10 May 2021) – Pierre Fabre today announced that the Scottish Medicines Consortium (SMC) has accepted BRAFTOVI^®q(encorafenib) plus cetuximab, within its marketing authorisation, as an option for treating BRAF^V600E mutation-positive metastatic colorectal cancer (mCRC), in adults who have had previous systemic treatment. This acceptance addresses the urgent need for effective and well-tolerated treatment options, since the current standard of care for these patients is chemotherapy-based regimens which have shown minimal response rates. Encorafenib plus cetuximab represents the first and only targeted combination regimen licensed in Europe specifically for BRAF^V600E mCRC, and is now funded on the NHS in Scotland.

“The SMC’s acceptance represents an important milestone for the colorectal cancer community in Scotland. In the past metastatic patients, with a BRAF^V600E mutation, have been treated with traditional, cytotoxic-based chemotherapy which generally offers low response rates. From today, the SMC allows us to access targeted medicines in these NHS Scotland patients,” said Dr Janet Graham, Consultant Medical Oncologist at Beatson West of Scotland Cancer Centre. “Given cytotoxic chemotherapy is associated with suppression of the immune system, the availability of this chemotherapy-free regimen is particularly pertinent as we continue to treat Scottish cancer patients amidst the COVID-19 pandemic.”

Genevieve Edwards, Chief Executive of Bowel Cancer UK, said: “We welcome the SMC’s acceptance of this targeted, combination therapy. Treatment options for the roughly one in ten people who are diagnosed with metastatic BRAF^V600E bowel cancer have been extremely limited to date. We worked alongside clinicians and patients to submit evidence to the SMC consultation, and we’re very pleased that the benefits have been recognised. This will give new hope to Scottish patients that could benefit.”

In Scotland, bowel cancer is the third most diagnosed cancer with approximately 3,700 new cases in 2017. Bowel cancer is the second most common cause of cancer death in Scotland with around 1,600 people dying from the disease each year. The five-year relative survival rate for bowel cancer is approximately 60% in Scotland, dropping to around one in ten for patients with metastatic disease throughout the UK.

The SMC’s acceptance is based on data from the pivotal, Phase 3 BEACON CRC trial, which met its primary endpoint. Results showed encorafenib plus cetuximab significantly improved median overall survival (OS) in patients with BRAF^V600E-mutant mCRC, and reduced the risk of death by 39%, compared to cetuximab plus irinotecan-containing regimens (control arm) (9.3 months vs 5.9 months; hazard ratio: 0.61; 95% confidence interval: 0.48–0.77; p<0.0001) [secondary endpoint]. 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 to the control arm [secondary endpoint].

The encorafenib plus cetuximab combination demonstrated a generally well-tolerated side effect profile, with the most common adverse drug reactions (>25%) observed in the BEACON CRC trial for encorafenib plus cetuximab being fatigue, nausea, diarrhoea, dermatitis acneiform, abdominal pain, arthralgia/musculoskeletal pain, decreased appetite, rash and vomiting. The rate of all study drug discontinuation due to any adverse reaction was 1.9 % in patients treated with encorafenib in combination with cetuximab.

“We are delighted that the SMC has recognised encorafenib plus cetuximab as a valuable treatment regimen for this high medical-need population,” said Laura McMullin, General Manager UK & Ireland, Pierre Fabre. “Securing NHS reimbursement in Scotland is the culmination of collaborative discussions with the SMC and we are grateful to the patient groups and clinical experts who strongly advocated for appropriate availability. Scottish patients now have access with immediate effect, in line with their counterparts throughout the UK. The acceptance is testament to our commitment to the colorectal cancer community and we hope that as many eligible patients as possible will benefit moving forwards.”

- ENDS –

NOTES TO EDITORS

About BRAF^V600E-mutant metastatic colorectal cancer

In Scotland, bowel cancer is the third most common cancer, with around 3,700 new cases diagnosed in 2017 – around 23-26% of bowel cancer patients have metastases at diagnosis. BRAF mutations are estimated to occur in approximately 8-12% of patients with mCRC, and V600E is the most common BRAF mutation.

Patients with mCRC who have BRAF^V600E-mutant tumours generally have a poor prognosis and represent an area of high unmet medical need. In a meta-analysis, the risk of mortality in mCRC patients with the BRAF^V600E mutation was more than two times higher than for those with wild-type BRAF (pooled hazard ratio: 2.25; 95% confidence interval: 1.82–2.83).

Bowel cancer is the second most common cause of cancer death in Scotland with around 1,600 people dying from the disease each year. The five-year relative survival rate for Scottish bowel cancer patients is approximately 60%, below the average for Europe according to some estimates. For metastatic disease, the five-year net survival is around one in ten for bowel cancer patients throughout the UK.

About the BEACON CRC trial

BEACON CRC is a randomised, open-label, global Phase 3 trial evaluating the efficacy and safety of encorafenib, with or without binimetinib, in combination with cetuximab in patients with BRAF^V600E-mutant mCRC whose disease has progressed after one or two prior regimens.

Encorafenib with binimetinib and cetuximab is not licensed for the treatment of BRAF^V600E -mutant mCRC.

BEACON CRC is the first and only Phase 3 trial designed specifically to test a BRAF combination targeted therapy in BRAF^V600E-mutant mCRC. A total of 665 patients were randomised 1:1:1 to one of the following treatment arms:

• Encorafenib 300 mg orally once daily in combination with cetuximab (encorafenib plus cetuximab arm)
• Encorafenib 300 mg orally once daily in combination with cetuximab and binimetinib (encorafenib plus cetuximab plus binimetinib arm). This combination used for the primary endpoint, is not the licensed indication
• Irinotecan with cetuximab or FOLFIRI (folinic acid, fluorouracil and irinotecan) 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 encorafenib plus binimetinib in combination with cetuximab versus the control arm. Secondary endpoints measured the overall survival efficacy of encorafenib in combination with cetuximab, compared with the control arm. 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, including five sites in the UK. 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 encorafenib

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 3 June 2020, encorafenib, in combination with cetuximab, received marketing authorisation from the European Commission (EC) for the treatment of adults with BRAF^V600E-mutant mCRC who have received prior systemic therapy.

On 20 September 2018, the EC granted marketing authorisations for encorafenib and binimetinib to be used in combination for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF^V600 mutation. The EC decision is applicable to all 27 EU member states as well as Iceland, Liechtenstein, Norway and the United Kingdom. Encorafenib and binimetinib have also received regulatory authorisation in the USA, Australia, Japan, Argentina and Switzerland.

On 27 June 2018, the combination of encorafenib and binimetinib was authorised by the FDA for the treatment of unresectable or metastatic melanoma with a BRAF^V600E or BRAF^V600K mutation, as detected by an FDA-approved test. Encorafenib and binimetinib are not indicated for treatment of patients with wild-type BRAF melanoma.

On 8 April 2020, the US FDA granted the license for encorafenib, in combination with cetuximab, for the treatment of adult patients with mCRC with a BRAF^V600E mutation, as detected by an FDA-approved test, after prior therapy. Encorafenib is not indicated for treatment of patients with wild-type BRAF CRC.

Pfizer has exclusive rights to encorafenib in the USA and Canada. Pfizer has granted Ono Pharmaceutical Co. Ltd. exclusive rights to commercialise encorafenib in Japan and South Korea; Medison exclusive rights to commercialise encorafenib in Israel; and Pierre Fabre exclusive rights to commercialise encorafenib in all other countries in Africa, Asia (excluding Japan and South Korea), Europe, and Latin America.

About Pierre Fabre

Pierre Fabre is a French health and beauty care company with 35-years of experience in innovation, development, manufacturing and commercialization in oncology, and 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 medical franchises and international brands, including Pierre Fabre Oncology, Pierre Fabre Dermatology, Eau Thermale Avène, Klorane, Ducray, René Furterer, A-Derma, Naturactive, Pierre Fabre Oral Care.

The company has recently reaffirmed oncology as one of its main R&D and commercial priorities, focusing on targeted therapies, biotherapies and immuno-oncology. Its therapeutic areas cover high unmet medical needs, including colorectal, breast, lung cancers, melanoma and pre-cancerous conditions like actinic keratosis.

In 2020, Pierre Fabre generated €2.2 billion in revenues, 65% of which came from international sales.

Established in the South-West of France since its creation, the Group manufactures over 95% of its products in France and employs some 10,000 people worldwide. Its products are distributed in about 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.

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