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欧洲推荐批准Kisplyx用于晚期肾细胞癌上市许可

2016-09-04 04:38:01 作者：新特药房来源：互联网浏览次数：8 文字大小：【大】【中】【小】

简介：新型抗癌药乐伐替尼(Kisplyx)，新适应症获欧洲药品管理局人用药品委员会的积极意见与依维莫司联合用药治疗晚期肾细胞癌2016年7月22日，欧洲药品管理局人用药品委员会（CHMP）对抗癌药甲磺酸乐伐替尼（通 ...

关键字：乐伐替尼硬胶囊lenvatinib 商品名Kisplyx 治疗晚期肾细胞癌

新型抗癌药乐伐替尼(Kisplyx)，新适应症获欧洲药品管理局人用药品委员会的积极意见与依维莫司联合用药治疗晚期肾细胞癌
2016年7月22日，欧洲药品管理局人用药品委员会（CHMP）对抗癌药甲磺酸乐伐替尼（通用名：乐伐替尼）的积极意见，其与依维莫司联合用药，治疗既往接受过血管内皮生长因子靶向疗法的晚期肾细胞癌成人患者。
如果获批，乐伐替尼将针对此适应症以Kisplyx®作为商品名上市
CHMP的积极意见主要基于一项评估乐伐替尼与依维莫司联合使用，治疗既往接受过血管内皮生长因子靶向疗法的患有不可切除的晚期或转移性肾细胞癌患者的安全性和有效性的II期临床研究（205试验）。
研究结果显示，与单独使用依维莫司治疗组相比，联合使用乐伐替尼和依维莫司治疗组的无进展生存期（研究主要终点）显著延长，且客观缓解率提高。乐伐替尼与依维莫司联合用药治疗组最常见的治疗中出现的不良反应包括腹泻、食欲不振和疲劳。
最常见的3级或以上的治疗中出现的不良反应包括腹泻、高血压和疲劳。
欧洲约有11.5万例肾细胞癌患者，肾细胞癌在所有肾癌患者中的比例超过90%。对于难以通过手术进行治疗的晚期或转移性肾细胞癌，标准疗法为分子靶向药物，但5年生存率很低，仍是一种亟需新的治疗选择的疾病。
目前，乐伐替尼已在美国、日本、欧洲，作为难治性甲状腺癌治疗药物，以Lenvima®为商品名上市。
另外，2016年5月，乐伐替尼在美国被FDA批准与依维莫司联合用药，治疗既往接受过血管内皮生长因子靶向疗法的晚期肾细胞癌患者。
Kisplyx将作为4毫克和10毫克/硬胶囊
lenvatinib mesylate (Kisplyx, Lenvima) (E7080)
Kisplyx® (lenvatinib) in Combination with everolimus Receives Positive CHMP Opinion in Advanced Renal Cell Carcinoma
About Lenvatinib's Novel Binding Mode (Type V)
Kinase inhibitors are categorized into several types (Type I to Type V) depending on the binding site and the conformation of the targeted kinase in complex with them. Most of the currently approved small molecule kinase inhibitors are either Type I or Type II, however lenvatinib was found to possess a new binding mode (Type V) of kinase inhibition that is distinct from existing compounds. In addition, lenvatinib was confirmed via kinetic analysis to exhibit rapid and potent inhibition of kinase activity, and it is suggested that this may be attributed to its novel binding mode.
About Everolimus
Everolimus is a selective mTOR (mammalian target of rapamycin) inhibitor. mTOR is a key serine-threonine kinase, the activity of which is known to be upregulated in a number of human cancers.
About Advanced Renal Cell Carcinoma
Renal cell carcinoma originates in the lining of the tubules,[9] the very small tubes in the kidney along with other parts of the nephron are involved in the blood filtration process to remove waste products.
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New Drugs Online Report for lenvatinib
Information
Generic Name: lenvatinib
Trade Name: Kisplyx
Entry Type: Licence extension / variation
Development and Regulatory status
UK: Recommended for approval (Positive opinion)
EU: Recommended for approval (Positive opinion)
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Jul 16: EMA grant positive opinion for MA Kisplyx for the treatment of patients with unresectable advanced or metastatic renal cell carcinoma [6].
26/07/2016 11:11:04
May 16: Approved in the US [5].
16/05/2016 14:10:21
Jan 16: Filed in the US, and granted priority review, for use in patients with unresectable advanced or metastatic RCC in combination with everolimus following one prior VEGF-targeted therapy [4].
20/01/2016 11:28:36
Jan 16: Filed in EU. EMA granted accelerated review to lenvatinib in October [3].
13/01/2016 10:10:53
Jul 15: The FDA has granted Eisai’s promising cancer drug lenvatinib (Lenvima) breakthrough therapy designation for renal cell carcinoma [1].
30/07/2015 15:26:09
Trial or other data
Jul 15: Breakthrough Therapy designation was based on the results of a PII trial (Study 205). Results published in J Clin Oncol. Study 205 was a multicenter, randomised, open-label study of lenvatinib (18 mg) in combination with everolimus (5 mg), lenvatinib alone (24 mg), and everolimus alone (10 mg) in patients with advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the safety and efficacy of these three regimens. From the results of the study, the combination of lenvatinib plus everolimus demonstrated a significant extension in the study´s primary endpoint of progression free survival (PFS) compared to everolimus alone (median PFS for the lenvatinib plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p<0.001). Additionally, median PFS for lenvatinib alone was 7.4 months, demonstrating an extension in PFS compared to everolimus alone (HR: 0.61 [95% CI: 0.38-0.98]). The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the lenvatinib plus everolimus group and the lenvatinib alone group showed an improvement in ORR compared to the everolimus alone group (lenvatinib plus everolimus: 43%, lenvatinib alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, an updated analysis carried out in December 2014 suggested that lenvatinib plus everolimus extends OS compared to everolimus alone (HR 0.51 [95% CI=0.30-0.88]). The most common treatment-emergent adverse events (TEAE) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher included diarrhea, hypertension and fatigue [2].
30/07/2015 15:37:43
Evidence Based Evaluations
NIHR HSRIC http://www.hsric.nihr.ac.uk/topics/lenvatinib-in-combination-with-everolimus-for-advanced-or-metastatic-renal-cell-carcinoma-second-line/
References
Available only to registered users
Category
BNF Category: Other antineoplastic drugs (08.01.05)
Pharmacology: A multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of several receptors involved in tumour proliferation [1]
Epidemiology: Renal cell carcinoma comprises more than 90% of all malignancies of the kidney and is thought to affect 338,000 people worldwide [1]
Indication: Renal cell carcinoma
Additional Details: advanced and/or metastatic, combination therapy with everolimus - second-line therapy or greater
Method(s) of Administration
Oral
Company Information
Name: Eisai
US Name: Eisai
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Awaiting Update
Tariff Chemotherapy is locally negotiated
Implications Available only to registered users