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新类抗基底细胞癌药物Odomzo(sonidegib)获FDA批准即将上市

2015-07-26 11:05:44 作者：新特药房来源：互联网浏览次数：59 文字大小：【大】【中】【小】

简介： 2015年7月24日,美国食品和药品监督管理局(FDA)批准Odomzo(sonidegib)治疗有局部晚期基底细胞癌患者手术或放疗后复发，或不是对手术或放疗被选者。皮肤癌是最常见癌而基底细胞癌约占非-黑色素瘤皮肤癌的8 ...

关键字：sonidegib商品名odomzo 治疗晚期最常见皮肤癌晚期基底细胞癌刺猬信号通路

2015年7月24日,美国食品和药品监督管理局(FDA)批准Odomzo(sonidegib)治疗有局部晚期基底细胞癌患者手术或放疗后复发，或不是对手术或放疗被选者。
皮肤癌是最常见癌而基底细胞癌约占非-黑色素瘤皮肤癌的80%。基底细胞癌开始在皮肤的顶层(被称为表皮)和通常发生在曾被经常暴露在阳光下和紫外辐射的其他形式的区域。按照美国国家癌症研究所，非-黑色素瘤皮肤癌的新病例数似乎每年增加。局部地晚期基底细胞皮肤癌指基底癌尚未播散至机体其他部位，但不能用局部治疗根治，特别是手术和辐射。
Odomzo是一种药丸每天服用1次。它通过抑制一种分子途径作用，被称为刺猬信号通路[Hedgehog pathway]，在基底细胞癌中活化。通过抑制这个通路，Odomzo可能停止或减低癌性病变的生长。
FDA的药品评价和研究中心血液学和肿瘤室主任Richard Pazdur，M.D.说：“我们对涉及癌症分子途径了解的增加导致在难以治疗疾病中许多肿瘤药物的批准其中少数治疗选择以前存在，” “感谢对刺猬信号通路的更好了解，只是在过去三年，FDA现已两个药物为基底细胞癌的治疗。”在2012年，Erivedge(维莫德吉[vismodegib]是被批准治疗局部晚期和转移基底细胞癌第一个药物。
Odomzo携带一个黑框警告警示卫生保健专业人员当给予妊娠妇女Odomzo可能致在发育的胎儿中死亡或严重出生缺陷。Odomzo治疗的开始前妊娠状态应被验证，和男性和女性患者都应被警告关于这些风险和忠告使用有效避孕。
Odomzo的疗效was established 在一项多中心，双盲临床试验，其中66例患者有局部晚期基底细胞癌被随机地赋予接受Odomzo 200 mg每天和128例患者被赋予接受Odomzo 800 mg每天。研究的主要终点是客观反应率，它是他们的肿瘤经历部分收缩或完全消失患者的百分比。结果显示用Odomzo 200 mg治疗患者有58%有他们的肿瘤收缩或消失。这个效应至少持续1.9至18.6个月，和反应肿瘤收缩患者约半数持续6个月或更长。接受Odomzo 800 mg每天患者中反应率相似，但是在这个剂量时副作用更常见。
在剂量200mg每天时， Odomzo的最常见副作用是肌肉痉挛，脱发，味觉障碍(味觉失真)，疲乏，恶心，肌肉骨骼痛，腹泻，体重减轻，食欲减退，肌肉痛，腹痛，头痛，疼痛，呕吐和瘙痒。Odomzo还有潜力致严重肌肉骨骼相关副作用，包括血清肌酐激酶水平增加[有罕见肌肉组织分解报告(横纹肌溶解症)]，肌肉痉挛，和肌肉痛。
Odomzo 是由总部在新泽西州East Hanover的Novartis Pharmaceuticals Corporation上市。Erivedge是有加州旧金山的 Genentech上市。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455862.htm
New Drugs Online Report for sonidegib
Information
Generic Name: sonidegib
Trade Name: Odomzo
Synonym: LDE225, erismodegib
Entry Type: New molecular entity
Development and Regulatory status
UK: Recommended for approval (Positive opinion)
EU: Recommended for approval (Positive opinion)
US: Pre-registration (Filed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Jun 15: EU positive opinion for treatment of adults with locally advanced BCC who are not amenable to curative surgery or radiation therapy [13].
26/06/2015 12:22:38
Q3 14: Filed in the US [11].
18/12/2014 13:51:03
Jun 14: Filed in the EU under the centralised procedure, using the name sonidegib [10].
03/07/2014 15:56:19
Apr 12: Filing for BCC now planned for 2014 [7].
12/06/2012 14:36:17
PII study started Apr 11 [6].
16/08/2011 10:38:53
Filings now expected 2012 (5).
02/12/2010 15:33:23
Filings now planned for 2011 (4).
11/06/2010 12:39:26
Filing planned 2010 (1).
22/03/2010 13:55:11
Trial or other data
May 15: Results of PII BOLT trial published in The Lancet Oncology [12].
17/05/2015 18:50:02
Feb 14: The pivotal PII trial met its primary endpoint of demonstrating an objective response rate (complete and partial response) among patients within six months of treatment. The randomized, double-blind BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) study was designed to assess the safety and efficacy of two oral dose levels of LDE225 (200mg and 800mg) in patients with locally advanced or metastatic basal cell carcinoma [9]
20/02/2014 09:41:57
NCT01327053: PII study will assess the efficacy and safety of two doses of oral LDE225 in patients with locally advanced or metastatic BCC [8].
21/09/2012 09:12:55
NCT00961896 PII study to evaluate the safety, local tolerability, pharmacokinetics and pharmacodynamics of multiple topical administrations of LDE225 (0.25% and 0.75%) on skin basal cell carcinomas in 18 patients with Gorlin´s syndrome [8]
21/09/2012 09:10:40
NCT01350115: A PII double-blind, 12 week Proof of Concept RCT to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of LDE225 in treatment of skin basal cell carcinomas in 42 adults with Nevoid Basal Cell Carcinoma Syndrome (NBCCS). A long-term follow-up period for safety and disease burden assessment is planned after the end of the core study. The study will test different doses vs placebo. Primary outcome is clinical response. The study started in Apr 11 and is due to complete Dec 11 [6].
16/08/2011 10:38:29
Gorlin´s syndrome is an inherited condition and pts with it are predisposed to a number of different medical conditions incl. basal cell skin cancer, skin tags, skin cysts, medulloblastoma (PNET) and benign ovarian tumours. PNET develops in 1 in 20 people who have Gorlin´s syndrome (2).
22/03/2010 14:05:41
Mar 09: the first-in-human dose-escalation open-label study (NCT00880308) of LDE225 began to investigate the safety, tolerability, pharmacokinetics & pharmacodynamics of LDE225 in adult pts with advanced solid tumors (incl medulloblastoma & basal cell carcinoma). The trial will enrol 58 pts in the UK, Spain and the US, and will complete in Dec 10 (3).
22/03/2010 14:03:04
Evidence Based Evaluations
NHSC References
Available only to registered users
Category
BNF Category: Other antineoplastic drugs (08.01.05)
Pharmacology: Smoothened (Smo) protein antagonist. Smo is a G protein-coupled receptor-like molecule that is essential to the actions of the Hedgehog family of secreted proteins.
Epidemiology: In 2010, 99,549 cases of non-melanoma skin cancer were registered in the UK. The metastatic rate of BCC is between 0.0028% and 0.5%7. The time from initial tumour to metastasis is about 9 years and median survival ranges from 8 months in etastatic disease to 3.6 years in locally advanced disease7. ~ 90% of people with BCC will achieve a complete cure (www.nhs.uk/conditions/Cancer-ofthe-kin/Pages/Introduction.aspx) Gorlin syndrome is a rare condition, affecting about 1 in 57,000 people
Indication: Basal cell carcinoma
Additional Details: advanced, including Gorlin syndrome
Method(s) of Administration
Oral
Topical
Company Information
Name: Novartis
US Name: Novartis
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Awaiting Update
Tariff Chemotherapy is locally negotiated.
Implications Available only to registered users