Dabrafenib: First Global Approval
Dabrafenib: First Global Approval
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DOI：
10.1007/s40265-013-0095-2
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发表时间：
2013-08-01
期刊：
影响因子：
11.5
通讯作者：
Garnock-Jones, Karly P.
中科院分区：
文献类型：
--
作者：
Ballantyne, Anita D.;Garnock-Jones, Karly P.
突变的BRAF激酶抑制剂达普拉非尼(Tafinlar(R))是葛兰素史克公司为发现突变的BRAF激酶活性的选择性抑制剂而进行的研究计划中推出的，用于治疗实体肿瘤；BRAF基因的突变与癌细胞的生长和增殖增加有关。葛兰素史克公司已将达普拉非尼的开发重点放在恶性黑色素瘤的治疗上，因为在这些癌症中有50%存在BRAF突变。达普拉非尼在美国被批准为治疗BRAF V600E突变患者中无法切除或转移性黑色素瘤的单一药物，并在欧盟这一适应症中获得了积极的评价。美国和欧盟也提交了将达普拉非尼与曲美替尼联合用于治疗具有BRAF V600E/K突变的转移性黑色素瘤的意见书。达普拉非尼作为单一疗法和联合疗法治疗恶性黑色素瘤的全球第三阶段开发正在进行中。第二阶段的开发正在进行中，用于治疗已转移到大脑的恶性黑色素瘤，以及结直肠癌和非小细胞肺癌。达普拉非尼用于治疗BRAF V600E/K突变患者。葛兰素史克在美国的达普拉非尼应用包括通过美国FDA批准的测试检测到的对这一人群的治疗。葛兰素史克与BioMerieux和Response Genetics合作，开发了一种分子治疗测试，以确定BRAF V600E/K突变。FDA已经批准了这项测试的上市前批准。这篇文章总结了达普拉非尼开发的里程碑，导致首次被批准为治疗BRAF V600E突变患者无法切除或转移性黑色素瘤的单一药物。
Dabrafenib (Tafinlar (R)), a mutant-BRAF kinase inhibitor, emerged from GlaxoSmithKline's research programme for the discovery of selective inhibitors of mutant BRAF kinase activity, for the treatment of solid tumours; mutations in the BRAF gene are associated with increased growth and proliferation of cancer cells. GlaxoSmithKline has focused the development of dabrafenib on the treatment of malignant melanoma, as BRAF mutations are present in 50 % of these cancers. Dabrafenib is approved in the US as a single agent treatment for unresectable or metastatic melanoma in patients with the BRAF V600E mutation, and has received a positive opinion in the EU in this indication. Submissions have also been made in the US and the EU for the use of dabrafenib in combination with trametinib for the treatment of metastatic melanoma with a BRAF V600E/K mutation. Global phase III development of dabrafenib as a monotherapy and as a combination therapy is ongoing in the treatment of malignant melanoma. Phase II development is ongoing for the treatment of malignant melanoma that has metastasised to the brain, and for colorectal and non-small cell lung cancers. Dabrafenib is intended to treat the patient population with a BRAF V600E/K mutation. GlaxoSmithKline's dabrafenib application in the US included the treatment of this population as detected by a US FDA-approved test. GlaxoSmithKline, in collaboration with bioMerieux and Response Genetics, has developed a molecular theranostic test to identify BRAF V600E/K mutations. Pre-Market approval of the test has been granted by the FDA. This article summarises the milestones in the development of dabrafenib leading to this first approval as a single agent treatment for unresectable or metastatic melanoma in patients with the BRAF V600E mutation.