英文药名: Firmagon (Degarelix)

中文药名: 地加瑞克, 地盖瑞利注射剂

品牌药生产厂家: Ferring Pharmaceuticals Inc

药品简介

美国FDA批准Ferring Pharmaceuticals公司degarelix粉针剂（Tradename/Firmagon）上市，用于治疗晚期前列腺癌。
本品剂量规格：degarelix 80 mg、120 mg/瓶。80 mg瓶含甘露醇 200 mg，120 mg瓶含甘露醇 150 mg。
本品系一促性腺激素释放激素（GnRH）受体抑制剂类药物，可逆性抑制垂体GnRH受体来减少促性腺激素释放继而抑制睾酮的释放。本品通过抑制对前列腺癌持续生长至关重要的睾酮来延缓前列腺癌的生长和恶化。以激素治疗前列腺癌来降低睾酮浓度的初期却造成睾酮浓度激增，此初始刺激该激素受体可暂时性促进肿瘤生长而不是抑制它。而地degarelix则不会。
Ⅲ期临床研究显示，本品降低睾酮浓度的效果至少可与亮丙瑞林储库型控释注射剂（Lupron Depot）相媲美，而且降低睾酮浓度在统计学上显著快。在治疗的第3日，本品组96％达到去生殖腺的睾酮浓度，亮丙瑞林组效果为0％。第14日，本品组99％达到去生殖腺的睾酮浓度，亮丙瑞林组为18％。
在临床研究中，前列腺特异抗原（PSA）浓度可作为监测的第2个疗效判断终点。使用degarelix2周后降低PSA 64％，1月后85％，3月后95％，在治疗的整个1年中始终抑制PSA。
本品在临床研究中报道的最常见的不良反应是注射部位反应（疼痛，红肿和肿胀），热潮红，体重增加，乏力和某些肝酶浓度升高。

FIRMAGON（degarelix）粉末，计量

生产商：辉凌制药公司

FIRMAGON ®（注射用degarelix）皮下给药。

初步U. S.批准：2008

适应症

FIRMAGON是GnRH受体拮抗剂治疗晚期前列腺癌患者的指示。
 
剂量和用法

FIRMAGON皮下给药和不静脉给药。

治疗开始用注射，每次120毫克的剂量为240毫克。

其次是维护管理作为一个单一的注射，每28天80毫克的剂量起始剂量。
 
剂型和优势
FIRMAGON（注射degarelix）120毫克每小瓶

FIRMAGON（注射degarelix）80毫克每小瓶
 
禁忌
Degarelix禁忌：

患者与以前的过敏反应FIRMAGON。

时可能发生的对孕妇怀孕等级X的胎儿造成伤害。
 
警告和注意事项
长期雄激素剥夺治疗的QT间隔延长。考虑风险和收益。

不良反应
FIRMAGON治疗期间最常观察到的不良反应（> 10％），包括注射部位反应（如疼痛，红斑，肿胀，或硬结），潮热，体重增加，血清转氨酶和γ-谷氨酰转肽酶（GGT增加）。 

药物相互作用
临床显着的细胞色素P450的药代动力学药物相互作用是不可能的。
 
在特殊人群中使用
有老人或轻度或中度肝或肾功能损害患者无需调整剂量。严重肝或肾功能不全患者进行了研究，因此值得谨慎。
 

修订日期：09/2010

Ferring Pharmaceuticals Announces Immediate Availability of Degarelix for the Treatment of Advanced Prostate Cancer

Ferring Pharmaceuticals, USA today announced the U.S. commercial availability of degarelix for injection (trade name pending), a new injectable gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the U.S. Food and Drug Administration (FDA) for the treatment of hormone sensitive advanced prostate cancer. Degarelix is available for order through traditional and specialty pharmacy distributors.

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Degarelix provides fast, long-term suppression of testosterone, a hormone that stimulates prostate cancer growth.(1-3) Clinical trials demonstrated that degarelix is effective in quickly reducing and sustaining castrate levels of testosterone.(2,3) Degarelix works differently than a luteinizing hormone-releasing hormone (LHRH) agonist bybinding immediately and reversibly to GnRH receptors in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone. In the Phase III study vs. leuprolide, the degarelix group achieved a 90 percent decrease in median testosterone levels at Day 3 of treatment, compared with the leuprolide group, which experienced a 65 percent increase in median testosterone levels. By Day 3, 96 percent of degarelix patients achieved castrate levels of testosterone, compared with zero percent receiving leuprolide. In addition, degarelix was as effective as leuprolide in suppressing testosterone levels from Day 28 to the end of the study (Day 364), with 97.2 percent of the degarelix patients maintaining medical castrate levels compared with 96.4 percent for leuprolide.

Study findings also showed that prostate specific antigen (PSA) levels were lowered by 64 percent two weeks after administration of degarelix, 85 percent after one month, 95 percent after three months, and remained suppressed throughout the one year of treatment.(1,2) These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to aclinicalbenefit."Degarelix, the lead product in our urology portfolio,demonstrated both a rapid onset of action and a profound long-term suppression of testosterone," said Wayne Anderson, President and CEO Ferring Pharmaceuticals Inc., USA. "Now, advanced prostate cancer can be treated with a direct-acting GnRH receptor antagonist inducing rapid reduction of testosterone and sustaining those levels over time, meeting the goals of systemic therapy. We are excited to provide this effective new treatment option for men fighting advanced prostate cancer."Approved by the FDA on December 24, 2008, degarelix represents Ferring Pharmaceuticals' first global launch and the second urology product launch for Ferring Pharmaceuticals, USA. The European Commission granted marketing authorization for degarelix on February 19, 2009. Degarelix is awaiting approval in other key global markets.

Phase III Study Results
The 12-month, randomized, open-label, parallel-group Phase III study evaluated the efficacy and safety of degarelixcompared with leuprolide administered monthly over one year of prostate cancer treatment. Patients with histologically confirmed prostate cancer were randomized to either degarelix or leuprolide: a degarelix subcutaneous (under the skin) injection of 240 mg for one month with monthly maintenance doses of 80 mg (n=207) or monthly intramuscular (into the muscle) injections of leuprolide depot 7.5 mg (n=201).

The primary endpoint was testosterone suppression to less than or equal to 50 ng/dL during monthly measurements from Day 28 to Day 364. Degarelix was at least as effective as leuprolide in achieving and maintaining castrate levels of testosterone.
                               N          Patients with         % (95% CI)
                                       treatment response
Degarelix                 207               202                97.2
240/80 mg
Leuprolide 7.5 mg         201               194                96.4

Suppression of testosterone levels to less than or equal to 50 ng/dL occurred significantly faster in patients receiving degarelix than in those receiving leuprolide. At Day 3 of treatment, the degarelix group achieved a 90 percent decrease in median testosterone levels, compared to the leuprolide group which experienced a 65 percent increase in median testosterone levels.

The most commonly observed adverse reactions during degarelix therapy included injection site reactions (e.g. pain, erythema, swelling or induration), hot flashes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Ninety-nine percent of these observed adverse reactions were Grade 1 or 2 (mild to moderate). Specifically relating to the injection site adverse reactions, most were transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 (severe) injection site reactions occurred in two percent or less
of patients receiving degarelix.

Degarelix is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components. Degarelix is not indicated in women or pediatric patients. Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients
with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.

About Degarelix
Degarelix is an injectable gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the U.S. Food and Drug Administration (FDA) for the treatment of hormone sensitive advanced prostate cancer. As a receptor antagonist, degarelix reversibly binds to the GnRH receptors in the pituitary gland, immediately suppressing the secretion of theluteinizinghormone (LH), follicle-stimulating hormone (FSH), and subsequently, testosterone levels.(4) Degarelix also reduces levels ofprostate-specific antigen (PSA). Unlike LHRH agonists, such as leuprolide, an established treatment for prostate cancer, degarelix does not induce an initial testosterone surge. Degarelix is administered monthly by subcutaneous injection. The starting dose is 240 mg, followed by monthly maintenance doses of 80 mg. Degarelix is available for order through traditional and specialty pharmacy distributors. The average monthly cost of one year of degarelix treatment is comparable to other hormone treatments for prostate cancer.
About Prostate CancerProstate cancer is the most common cancer, excluding skin cancers, and the second leading cause of cancer death in American men. About one man in six will be diagnosed with prostate cancer during his lifetime, and one in 35
will die of this disease.(5) Prostate cancer develops from cells in the prostate gland that begin to grow out of control. In most cases, prostate cancer grows slowly and can remain undetected throughout a man's life, although it can grow and spread quickly.(6) The four types of standard treatment are: watchful waiting, surgery, radiation therapy, and hormone therapy, also called androgen deprivation therapy (ADT).

Degarelix—晚期前列腺癌新选择

Ferring公司研发生产的Degarelix主要用于治疗晚期前列腺癌，并于2008年12月24日获得FDA的批准。它是近年来FDA批准的首个用于治疗前列腺癌的新药。该药的问世给晚期前列腺癌患者带来了新的福音，临床应用更为方便。

这一新药属于“促性腺激素释放激素(GnRH)”受体抑制剂类药物，主要针对晚期前列腺癌患者，通过抑制睾丸激素来延缓前列腺癌的病程发展。

前列腺癌是最为常见的癌症之一。美国药品评价与研究中心肿瘤药办公室主任、医学博士Richard Pazdur表示：“前列腺癌是美国男性的第二大‘癌症杀手’，这些患者需要更多的治疗选择。”

目前对于前列腺癌的治疗在不同阶段可以选择不同的治疗手段，包括前列腺切除术、放射疗法、化疗以及激素疗法。

以前治疗前列腺癌的激素疗法的特点是“先升后降”，即在治疗初期，某些疗法会导致患者的睾丸激素水平激增，然后才会显现疗效，降低睾丸激素水平。这意味着在治疗初期，肿瘤可能非但未受到抑制，反而被刺激生长。而Degarelix从一开始就能产生疗效，与目前已用于治疗晚期前列腺癌的激素药物Leuprolide的临床对比试验显示，Degarelix不会导致常见的睾丸激素“先升后降”现象。

FDA还表示，服用这两种药物的患者睾丸激素对癌症的治疗都能达到前列腺切除术相当的水平。

Degarelix原料药是一种合成的线状十肽酰胺，含有7个非天然的氨基酸，分子式是C82H103N18O16Cl，分子量为163203Da。

其制剂是可注射的冻干粉针，规格有80 mg和120 mg两种。

Degarelix 是一种促性腺激素释放素（GnRH）受体拮抗剂，能与脑垂体GnRH受体可逆结合，降低促性腺激素释放，因而使睾丸素释放减少，维持血浆睾丸素水平在去势水平（50 ng/dL）以下。

适用于晚期前列腺癌的治疗

推荐用法和剂量为：初始剂量240 mg，分2次皮下注射，每次120 mg，然后每28天给予维持剂量80mg或160 mg。

临床试验中以本品240/160 mg、240/80 mg与亮丙瑞林（Leuprolide）对照研究显示，治疗1年的主要终点血浆睾丸素达到并维持在去势水平以下（50 ng/dL）的患者百分率分别为98.3％、97.2％和96.4％；第二终点血浆PSA水平2周降低64％，一个月降低85％，三个月降低95％。

主要不良反应是注射部位反应（红、痛、肿或结硬），潮热，体重增加，血清转氨酶增加。

地盖瑞利注射剂-前列腺癌治疗效果更快更好

地盖瑞利能可逆性抑制垂体GnRH受体来减少促性腺激素释放继而抑制睾酮的释放，治疗前列腺癌的效果与亮丙瑞林储库型控释注射剂相当，但见效更快且更持久，用药3天可使96％达到去生殖腺的睾酮浓度。

随着医药技术的快速发展，越来越多的新型抗癌药物进入临床，日前，Ferring（辉凌）公司的新型抗癌药物-地盖瑞利注射剂Firmagon(Degarelix)获美国批准用于治疗晚期前列腺癌。

睾酮是前列腺癌持续生长至关重要的物质。目前，临床主要采用激素降低睾酮浓度来治疗前列腺癌，但初期往往造成睾酮浓度激增，因此初始刺激该激素受体可暂时性促进肿瘤生长而不是抑制它，但地盖瑞利却不会出现此种情况，它主要通过持续抑制睾酮来延缓前列腺癌的生长和恶化。

地盖瑞利是一种新型促性腺激素释放激素（GnRH）受体抑制剂类药物，能可逆性抑制垂体GnRH受体来减少促性腺激素释放继而抑制睾酮的释放。研究证明，地盖瑞利1年的治疗可快速有效且持续抑制睾酮和前列腺特异抗原（PSA），耐受性良好，且未见睾酮快速升高。

Ⅲ期临床研究显示，地盖瑞利降低睾酮浓度的效果至少可与亮丙瑞林储库型控释注射剂（LupronDepot）相媲美，而且降低睾酮浓度兼相爱哦更快。研究发现，在治疗的第3日，地盖瑞利组96％达到去生殖腺的睾酮浓度，亮丙瑞林组效果为0％。第14日，本品组99％达到去生殖腺的睾酮浓度，亮丙瑞林组为18％。

在临床研究中，前列腺特异抗原（PSA）浓度可作为监测的第2个疗效判断终点。结果显示，使用地盖瑞利2周后降低PSA64％，1月后85％，3月后95％，在治疗的整个1年中始终抑制PSA。临床研究中，地盖瑞利最常见的不良反应是注射部位反应（疼痛，红肿和肿胀），热潮红，体重增加，乏力和某些肝酶浓度升高。