关键词：葛兰素史克,黑色素瘤,Tafinlar,Mekinist,BRAF突变

2013年5月30日讯 /生物谷BIOON/ --葛兰素史克（GSK）29日宣布，2种黑色素瘤新药Tafinlar (dabrafenib) 和Mekinist (trametinib)均获得了FDA的批准。Tafinlar为BRAF抑制剂，作为一种单药口服胶囊，适用于携带BRAF V600E突变的手术不可切除性黑色素瘤或转移性黑色素瘤成人患者的治疗。Mekinist为首个MEK抑制剂，作为一种单药口服片剂，适用于携带BRAF V600E或V600K突变的手术不可切除性黑色素瘤或转移性黑色素瘤成人患者的治疗。

Tafinlar不适用于野生型BRAF黑色素瘤患者的治疗。
Mekinist不适用于既往接受过BRAF抑制剂疗法的患者的治疗。

这些突变，必须经由FDA批准的一款伴侣诊断试剂盒检测（THxID-BRAF，由BioMerieus开发）检测证实。

转移性黑色素瘤中，约有一半携带BRAF突变，该异常突变能促使黑色素瘤生长和扩散。Tafinlar和Mekinist分别获批用于携带BRAF V600E突变的患者，该突变约占转移性黑色素瘤所有BRAF V600突变的85%。Mekinist同时获批用于携带BRAF V600K突变的患者，该突变约占转移性黑色素瘤所有BRAF V600突变的10%。

基于临床试验中这2种药物的疗效及安全性数据，，作为获批的一部分，FDA也提出了相关警告及注意事项。Tafinlar 可能引发严重的副作用，其中一些可能危及生命，包括患新的原发性皮肤恶性肿瘤风险升高、野生型BRAF黑色素瘤中的肿瘤启动（tumour promotion）、严重的发热反应（严重发烧）、高血糖、葡萄膜炎、虹膜炎、葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症患者的溶血性贫血、生殖毒性（embryofoetal toxicity）。

Mekinist可能引发严重的副作用，其中一些可能危及生命，好医师网，包括心肌病（包括心脏衰竭）、视网膜色素上皮脱离（RPED）、视网膜静脉阻塞（RVO）、间质性肺病或肺炎、生殖毒性。

GSK称，将不迟于2013年第三季度将Tafinlar和Mekinist推向市场。

2010年，GSK与bioMérieux达成合作，开发用于检测BRAF V600突变（V600E和V600K）的伴侣诊断试剂盒。bioMérieux试剂盒THxID-BRAF已获得了FDA授予的上市前批准（pre-market approval），目前，该试剂盒是唯一获FDA批准的V600K突变检测试剂盒。（生物谷Bioon.com）

英文原文：Two new GSK oral oncology treatments, BRAF-inhibitor Tafinlar? (dabrafenib) capsules and the first MEK-inhibitor Mekinist? (trametinib) tablets, approved by FDA as single-agent therapies

-  Both approved for unresectable or metastatic melanoma with BRAF V600E mutation; Mekinist also approved for BRAF V600K mutation

Issued: 29 May 2013, London, UK and Philadelphia, U.S

GlaxoSmithKline plc [LSE/NYSE: GSK] announced today that the U.S. Food and Drug Administration (FDA) has approved both TAFINLAR? (dabrafenib) and MEKINIST? (trametinib). Tafinlar is indicated as a single-agent oral treatment for unresectable melanoma (melanoma that cannot be removed by surgery) or metastatic melanoma (melanoma which has spread to other parts of the body) in adult patients with BRAF V600E mutation. Tafinlar is not indicated for the treatment of patients with wild-type BRAF melanoma. Mekinist is indicated as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy. These mutations must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID?-BRAF.

“With today’s FDA approvals, GSK can now offer two new single-agent therapies to selected patients who have metastatic melanoma, a devastating disease with very low survival rates and few treatment options,” said Paolo Paoletti, M.D., President, GlaxoSmithKline Oncology. “GSK Oncology has been focused on progressing research in the most efficient manner possible, and we’re pleased to bring Tafinlar and Mekinist to physicians and their patients in rapid development times.”

Among those with metastatic melanoma, approximately half have a BRAF mutation, which is an abnormal change in a gene that can enable some melanoma tumours to grow and spread.[i]

Tafinlar and Mekinist are each approved for patients with the BRAF V600E mutation, which accounts for approximately 85 percent of all BRAF V600 mutations in metastatic melanoma.[ii] Mekinist is also approved for patients with the V600K mutation, which makes up approximately 10 percent of all BRAF V600 mutations in metastatic melanoma.2

“MEK has been pursued as a therapeutic target in cancer for more than a decade,” said Keith Flaherty, M.D., Director of Developmental Therapeutics, Massachusetts General Hospital Cancer Center, and principal investigator of the Phase III METRIC trial. “Based on the clear improvement versus chemotherapy in progression-free survival, trametinib represents the first validated MEK inhibitor. We welcome it as a new treatment option for patients with this disease.”

As part of the FDA approval, which was based on clinical studies evaluating the efficacy and safety of these products, warnings and precautions were also identified. Dabrafenib can cause serious side effects, some of which can be life threatening, including increasing the risk of developing new primary cutaneous malignancies (new skin cancers), tumour promotion in BRAF wild-type melanoma, serious febrile drug reactions (severe fevers), hyperglycaemia (blood sugar problems), uveitis and iritis (severe eye problems), haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and embryofoetal toxicity (potential harm to the unborn baby in pregnant women). Trametinib can cause serious side effects, some of which can be life threatening, including cardiomyopathy (heart problems, including heart failure), retinal pigment epithelial detachment (RPED) and retinal vein occlusion (RVO) (eye problems including blindness), interstitial lung disease or pneumonitis (lung or breathing problems), serious skin toxicity (rash) and embryofoetal toxicity.

GSK will be making Tafinlar and Mekinist available for prescription no later than in the early third quarter of 2013.

In 2010, GSK entered a collaboration with bioMérieux to develop a companion diagnostic test to detect BRAF V600 (V600E and V600K) gene mutations found in several cancers, including melanoma. bioMérieux has received FDA pre-market approval of THxID?-BRAF. Currently, it is the only FDA-approved test that detects the V600K mutation.

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