New clinical standard for RAF melanoma! The new targeted combination therapy Braftovi and Mektovi has been approved by NICE UK

France's Pierre Fabre recently announced that the UK's National Institute for Health and Clinical Optimization (NICE) has issued guidelines recommending a combination of Braftovi (binimetinib, a MEK inhibitor) and Mektovi (a BRAf inhibitor) for the treatment of adult patients with non-removable melanoma who have been tested for the BRAF V600 mutation. In the United States and the European Union, the portfolio was approved in June 2018 and September 2018, respectively, for the treatment of non-removable or metastasis melanoma patients who have been tested for BRAF V600E or V600K mutations. It is important to note that Braftovi is not suitable for the treatment of wild BRAF melanoma.
the Braftovi-Mektovi combination is based on the results of the Phase III clinical study COLUMBUS. Data show that compared to Roche's late melanoma specialty drug Zelboraf (vemurafenib, Verofenib), the Braftovi-Mektovi combination scheme (binimetinib 45mg twice a day and encorafenib 450mg once a day) makes no progress for life Significantly doubled (medium PFS: 14.9 months vs 7.3 months, HR:0.54, 95% CI:0.41-0.71, p<0.0001). In the study, only 5% of patients in the Braftovi-Mektovi programme group stopped treatment for adverse reactions, with the most common adverse reactions (≥25%) in the group being fatigue, nausea, diarrhea, vomiting, abdominal pain and joint pain.
total lifeseed (OS) analysis of COLUMBUS studies published in February 2018 shows that the Braftovi-Mektovi programme significantly reduces the risk of death compared to Zelboraf (960mg, once a day) (HR=0.61,95 %CI: 0.47-0.79, p<0.0001): Zelboraf single-drug group medium OS is 16.9 months, Braftovi and Mektovi scheme group mid OS is 33.6 months. These positive data further enhance the clinical evidence for BRAF/MEK inhibitor combination therapy.
industry believes that the Braftovi-Mektovi portfolio will compete in the late BRAF mutant melanoma segment, primarily for Novarma's Tafinlar-Mekinist solution. Jefferies, a well-known Wall Street investment bank, has previously said that the Braftovi-Mektovi portfolio could do better in this segment than Novarco's, which has annual sales of about $400m.
The Braftovi-Mektovi combination is the first targeted therapy to treat BRAF mutant melanoma for more than 30 months in Phase III clinical life, representing a new clinical care guarantee for BRAF mutant melanoma. With nearly half of patients diagnosed with metastasis melanoma detecting BRAF mutations, the approval of the Braftovi-Mektovi programme will be great news for the melanoma patient population and will meet a critical unseemly medical need in this group of patients.
Braftovi and Mektovi were developed by American biopharmaceutical company Array BioPharma, and Pierre Fabre of France has licensed exclusive commercial rights to both products in all countries except the United States, Canada, Israel, Japan, Korea, including Europe, Latin America and Asia (except Japan and Korea). Array reserves exclusive rights to 2 products in the United States and Canada, Israeli pharmaceutical company Medison authorizes exclusive commercialization rights for both products in Israel, and Ono Pharmaceuticals licenses the development and commercialization rights for both products in Japan and South Korea.
AND BRAF are key protein kinases in the MAPK signaling path (RAS-RAF-MEK-ERK). Studies have shown that this path path is regulating a variety of key cell activities, including cell proliferation, differentiation, survival, and angiogenesis. In many cancers, such as melanoma, colorectal cancer, and thyroid cancer, proteins in this signaling pathline have been shown to be abnormally active.
binimetinib is a MEK inhibitor and encorafenib is a BRAF inhibitor, both of which target key enzymes in the signaling path. Currently, Array is also evaluating the potential of binimetinib and encorafenib to treat other types of cancer, including BRAF-mutated colorectal cancer. (Bio Valley)