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
FDA approves Novartis drug Odomzo® (sonidegib) for locally advanced basal cell carcinoma (laBCC), a form of skin cancer
- Approval is based on pivotal Phase II study in which objective response rate (ORR) in patients with laBCC was 58%; responses were durable(1)
- Basal cell carcinoma, the most common form of skin cancer, can be highly disfiguring at advanced stages(2)
- Odomzo adds to company's expanding portfolio of targeted treatments for skin cancer
EAST HANOVER, N.J., July 24, 2015 /PRNewswire/ -- Novartis today announced the US Food and Drug Administration (FDA) has approved Odomzo® (sonidegib, formerly LDE225) 200 mg capsules 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.
"The FDA approval of Odomzo offers a new and non-invasive treatment option for a potentially devastating disease that is hard to treat and can be disfiguring," said Bruno Strigini, President, Novartis Oncology. "Odomzo is an important addition to our growing portfolio of targeted treatments for advanced skin cancers and underscores our commitment to developing and bringing to market new options for patients."
The Odomzo approval was based on the demonstration of a durable objective response rate (ORR) in an international, multi-center, double-blind, randomized, two-arm, non-comparative trial in patients with laBCC not amenable to local therapy or metastatic basal cell carcinoma (mBCC).1
Patients with laBCC treated with Odomzo 200 mg (n=66) were followed for at least 12 months unless discontinued earlier. The ORR was 58% (95% confidence interval: 45, 70), consisting of 5% (n=3) complete responses (CR) and 53% (n=35) partial responses (PR). A pre-specified sensitivity analysis using an alternative definition for CR, defined as at least a PR according to MRI and/or photography and no evidence of tumor on biopsy of residual lesion, yielded a CR rate of 20%.1 Among the 38 patients with an objective response, 31 patients (82%) have ongoing responses ranging from at least 1.9 to 18.6 months and the median duration of response has not been reached.1
The most serious risks of Odomzo are embryofetal toxicity and musculoskeletal adverse reactions including rhabdomyolysis. Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations, may occur with Odomzo and other drugs which inhibit the hedgehog pathway. The incidence of musculoskeletal adverse reactions in patients with laBCC treated with Odomzo 200 mg was 68%, with 9% reported as grade 3 or 4. Adverse reactions occurring in more than 10% of patients treated with Odomzo 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. The most frequent grade 3 and 4 laboratory abnormalities occurring in at least 5% of patients were serum creatine kinase (CK) elevation and lipase elevation.1
About the BOLT Clinical Trial
Data from the Phase II, randomized, double-blind multicenter BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) formed the basis of the FDA's approval. The primary endpoint was ORR of patients treated with Odomzo 200 mg and 800 mg, defined as the proportion of patients with confirmed complete or partial tumor response, or shrinkage, as measured by a central review committee. There was no evidence of better ORR among patients with laBCC randomized to receive Odomzo 800 mg daily.1
The eva luation of tumor response was based on a composite assessment of modified Response eva luation Criteria in Solid Tumors (mRECIST) that integrated tumor measurements obtained by radiographic assessments of target lesions (per RECIST 1.1), digital clinical photography (World Health Organization (WHO) adapted criteria), and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of CR.1
Please visit http://www.pharma.us.novartis.com/product/pi/pdf/odomzo.pdf for Odomzo full Prescribing Information.
About Basal Cell Carcinoma
BCC consists of abnormal, uncontrolled growths or lesions that arise in the skin's basal cells, which line the deepest layer of the epidermis (the outermost layer of the skin)6 and accounts for more than 80% of non-melanoma skin cancers.7 It occurs most frequently on the head and neck, with the nose being the most common site.7 BCC that spreads from where it started to nearby tissue is called locally advanced8 and can be highly disfiguring.2 Advanced BCC is thought to represent roughly 1–10% of all cases of BCC. 9-11 While BCC is generally diagnosed and treated early, it may recur in an estimated 3% of patients after five years. 12 Although BCC rarely becomes advanced, there have been few treatment options at this stage of the disease. Worldwide incidence of BCC is rising by 10% each year due to factors such as an aging population and increased ultraviolet exposure. Incidence rates are estimated to be between 0.003% and 0.55% worldwide.13
About Odomzo
Odomzo (sonidegib, formerly LDE225) is an oral, selective smoothened (SMO) inhibitor approved by the FDA 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. 1 SMO is a molecule that regulates the hedgehog (Hh) signaling pathway, which plays a critical role in stem cell maintenance and tissue repair, as well as in advanced basal cell carcinoma3-5. Odomzo is currently in clinical development in other diseases.
Odomzo was approved in Switzerland for the treatment of advanced BCC that is not amenable to curative surgery or radiotherapy on June 30, 2015. The CHMP granted a positive opinion on June 25, 2015. Additional regulatory submissions are being reviewed by health authorities worldwide.
IMPORTANT SAFETY INFORMATION
Odomzo can cause a patient's baby to die before it is born (be stillborn) or cause a patient's baby to have severe birth defects.
Females who can become pregnant should talk to their doctor about the risks of Odomzo to their unborn child. Before starting Odomzo females who can become pregnant should have a pregnancy test. Birth control should be used during Odomzo treatment and for at least 20 months after the final dose of Odomzo. Patients should talk to their doctor right away if they have unprotected sex or think they may be pregnant.
Males taking Odomzo should not donate semen while taking Odomzo and for at least 8 months after their final dose. Also, males taking Odomzo should always use a condom, even if they have had a vasectomy, during sex with a female partner who is pregnant or can become pregnant during treatment with Odomzo and for at least 8 months after their final dose. Patients should talk to their doctor right away if they are taking Odomzo and their partner becomes pregnant or thinks she is pregnant.
Patients should not donate blood or blood products while taking Odomzo or for 20 months after their final dose of Odomzo.
Muscle spasms and muscle pain are common with Odomzo, but can also sometimes be symptoms of serious muscle problems. Odomzo can increase the risk of muscle pain and, rarely a serious condition caused by injury to the muscles (rhabdomyolysis) that can lead to kidney damage. Patients should tell their healthcare provider right away if they develop any new or worsening muscle spasms, pain or tenderness, dark urine, or decreased amount of urine during treatment with Odomzo. Their doctor should do a blood test to check for muscle problems and to check kidney function before starting Odomzo, during treatment, and if muscle problems develop.
Other common side effects of Odomzo include hair loss, change in taste, tiredness, nausea, diarrhea, weight loss, decreased appetite, stomach area (abdominal) pain, headache, vomiting, and itching.
Odomzo can cause absence of menstrual periods (amenorrhea) in females who are able to become pregnant. It is not known if amenorrhea is permanent. Patients should talk to their doctor for concerns about fertility. |
