2015年7月24日 - 美国食品和药物管理局今天批准Odomzo（sonidegib）治疗的患者已经复发手术或放射治疗，或谁是不适合手术或放射治疗局部晚期基底细胞癌。
皮肤癌是最常见的癌和基底细胞癌占大约80％的非黑素瘤皮肤癌。基底细胞癌开始于皮肤的顶层（称为表皮），通常在已经经常暴露在阳光和其它形式的紫外线辐射的区域发展。据美国国家癌症研究所，出现的非黑色素瘤皮肤癌的新发病例数每年都在增加。局部晚期基底细胞皮肤癌是指还没有扩散到身体的其他部位基底癌症，但不能与局部治疗，特别是手术和放射来治疗性治疗。
Odomzo是一天服用一次一丸。它的工作原理是通过抑制的分子途径，被称为Hedgehog通路，这是活跃在基底细胞癌。通过抑制该途径，Odomzo可能停止或减少癌病变的生长。
“我们越来越多参与癌症分子通路的认识，导致了许多肿瘤药物为其中一些治疗方法以前就存在难以治疗疾病的批准，”理查德Pazdur博士，医学博士，血液学和肿瘤学产品办公室主任中说FDA的药品评价中心和研究。“多亏了更好地了解Hedgehog通路中，FDA已经批准了现在两种药物基底细胞癌的治疗只是在过去的三年。”在2012年，Erivedge（vismodegib）被批准用于治疗局部晚期的第一个药物和转移性基底细胞癌。
Odomzo带有黑框警告提醒医疗专业人员当给予孕妇的Odomzo可能会导致发育中的胎儿死亡或严重出生缺陷。怀孕状况应Odomzo治疗开始前验证，男性和女性患者，应警告这些风险，并建议使用有效的避孕方法。
Odomzo的功效成立于一项多中心，双盲临床试验，其中66例局部晚期基底细胞癌患者随机分配到200毫克，每日接收Odomzo和128名患者被分配每天服用800 Odomzo毫克。该研究的主要终点是客观缓解率，这是谁经历局部收缩或他们的肿瘤（S）完全消失的患者百分比。结果表明，与Odomzo 200毫克治疗的患者58％有他们的肿瘤缩小或消失。这种效果持续了至少1.9至18.6个月，约一半的反应的患者“肿瘤缩小的历时半年或更长时间。反应率谁收到Odomzo 800毫克，每天的病人相似，但副作用是比较常见的，在这个剂量。
在200毫克，每日一剂，Odomzo的最常见的副作用是肌肉痉挛，脱发（脱发），味觉障碍（失真味觉），乏力，恶心，肌肉骨骼痛，腹泻，体重下降，食欲下降，肌痛（肌肉疼痛），腹痛，头痛，疼痛，呕吐，皮肤瘙痒（痒）。Odomzo也有可能造成严重的肌肉骨骼相关的副作用，包括增加的血清肌酸激酶水平[与肌肉组织分解罕见报告（横纹肌溶解）]，肌肉痉挛，和肌痛的潜力。
Odomzo由东汉诺威，新泽西州的诺华制药公司销售。Erivedge由Genentech公司在旧金山，加利福尼亚州销售。
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: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Jul 15: The FDA has approved Odomzo® for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. [14]
27/07/2015 10:30:47 
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
Jul 15: US approval of sonidegib (Odomzo) for basal cell carcinoma was based on clinical trials showing an overall response rate - the percentage of patients who experienced partial shrinkage or complete disappearance of their tumour - of 58% in those given the drug. This effect lasted at least 1.9 to 18.6 months, and around half of the responding patients’ tumour shrinkage lasted six months or longer. However, Odomzo carries a Boxed Warning that the drug may cause death or severe birth defects in a developing foetus when administered to a pregnant woman, and the incidence of musculoskeletal adverse reactions in patients taking part in trials was 68%, with 9% reported as grade 3 or 4. Also, adverse reactions occurring in more than 10% of patients treated with Odomzo were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus [15]. 
28/07/2015 15:59:53
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 eva luate 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 eva luate 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 eva luations
FDA doc  http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205266s000lbl.pdf 
NHSC  http://www.hsc.nihr.ac.uk/files/downloads/1989/2338.97d616b8.Erismodegib_Jan13.pdf
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