新型降胆固醇注射型药物Repatha（Evolocumab）获FDA批准为首个PCSK9抑制剂的上市新药
批准日期：2015年8月27日；公司：Amgen Inc.
REPATHA(evolocumab)注射液，为皮下使用
美国初次批准：2015
RepathaTM(evolocumab)是一种可抑制前蛋白转化酶枯草溶菌素/kexin9型(PCSK9)的全人源化单克隆抗体1。PCSK9是一种能够降解LDL受体，从而降低肝脏从血液中清除LDL-C或“坏”胆固醇的能力的蛋白18。Repatha由安进的科学家研发获得，用于结合PCSK9，从而抑制PCSK9与肝脏表面LDL受体的结合。在PCSK9缺失的条件下，肝脏表面的LDL受体水平更高，从而能够更有效地清除血液中的LDL-C1。
作用机制
Evolocumab是一种直接对人前蛋白转化酶枯草杆菌蛋白酶Kexin9(PCSK9)人单克隆IgG2。Evolocumab结合至PCSK9和抑制循环PCSK9避免结合至低密度脂蛋白(LDL)受体(LDLR)，阻止PCSK9-介导的LDLR降解和允许LDLR回收返回至肝细胞表面。通过抑制PCSK9结合至LDLR，evolocumab增加可得到从血液清除LDL的LDLRs数，因此降低LDL-C水平。
适应症和用途
REPATHA是一种PCSK9(人前蛋白转化酶枯草杆菌蛋白酶Kexin类型9)抑制剂抗体适用为一种对膳食辅助和：
●最大耐受他汀治疗有杂合子家族性高胆固醇血症(HeFH)或临床动脉粥样硬化心血管疾病(CVD)需要另外降低低密度脂蛋白胆固醇(LDL-C)成年的治疗。
● 其他降LDL治疗(如，他汀类，依泽替米贝[ezetimibe]，LDL血浆分离置换)在有纯合子家族性高胆固醇血症(HoFH)需要另外降低LDL-C患者.
使用限制
未曾确定REPATHA对心血管患病率和死亡率的影响。
剂量和给药方法
通过皮下注射给药
原发性高脂血症有确定的临床动脉粥样硬化CVD或HeFH：140mg每2周或420mg每月1次在腹部，大腿，或上臂。
HoFH：420mg每月1次.
给予420mg，在30分钟内连续给予3次REPATHA注射。
见剂量和给药方法对重要给药指导。
剂型和规格
注射液：140mg/mL在一个单次使用预装注射器.
注射液：140mg/mL在一个单次使用预装SureClick®自动注射器.
禁忌症
有对REPATHA严重过敏反应病史患者。
警告和注意事项
过敏反应：曾发生皮疹和荨麻疹。如发生严重过敏反应的体征或症状，终止用REPATHA治疗，按照标准医护，和监视直至体征和症状解决。
不良反应
在临床试验中常见不良反应(用REPATHA治疗患者>5%和比安慰剂发生更频)：鼻咽炎，上呼吸道感染，流感，背痛，和注射部位反应。
供应/贮存和处置
REPATHA是一个无菌，透明至乳白色，无色至淡黄色溶液为皮下注射在一个单次使用预装注射器或一个单次使用预装SureClick®自动注射器供应。每个REPATHA的单次使用预装注射器或单次使用预装SureClick®自动注射器被设计输送1mL的140mg/mL溶液。

药房
在原纸盒中贮存在冰箱在2°至8°C(36°至46°F)避光保护。不要冻结。不要摇晃。
对患者/护理人员
在原纸盒内贮存在冰箱2°至8°C(36°至46°F)。另外，REPATHA在原纸盒内可被保持在室温(至25°C(77°F))；但是，在这些条件下，REPATHA必须在30天内使用。如30天内未使用，遗弃REPATHA。
保护REPATHA避免光直接照和不要暴露在25°C(77°F)以上。

Important Safety Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions: Renal impairment: Patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2) have not been studied. Repatha should be used with caution in patients with severe renal impairment. Hepatic impairment: In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed that may lead to a reduced effect on LDL‑C reduction. Therefore, close monitoring may be warranted in these patients. Patients with severe hepatic impairment (Child-Pugh C) have not been studied. Repatha should be used with caution in patients with severe hepatic impairment. Dry natural rubber: The needle cover of the glass pre-filled syringe and of the pre-filled pen is made from dry natural rubber (a derivative of latex), which may cause allergic reactions. Sodium content: Repatha contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.
Interactions: No formal drug-drug interaction studies have been conducted for Repatha. No studies on pharmacokinetic and pharmacodynamics interaction between Repatha and lipid-lowering drugs other than statins and ezetimibe have been conducted.
Fertility, Pregnancy and Lactation: There are no or limited amount of data from the use of Repatha in pregnant women. Repatha should not be used during pregnancy unless the clinical condition of the woman requires treatment with evolocumab. It is unknown whether evolocumab is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. No data on the effect of evolocumab on human fertility are available.
Undesirable Effects: The following common (≥ 1/100 to < 1/10) adverse reactions have been reported in pivotal, controlled clinical studies: influenza, nasopharyngitis, upper respiratory tract infection, rash, nausea, back pain, arthralgia, injection site reactions. Please consult the SmPC for a full description of undesirable effects.
Pharmaceutical Precautions: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the pre-filled syringe or the pre-filled pen in the original carton in order to protect from light. If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 week.
Repatha (evolucomab)- First PCSK9 Inhibitor in the world is approved
First PCSK9 Inhibitor in the world is approved
We've seen the dawn of a new family of medicines to treat cholesterol. The European Commission (agency analogous to the FDA in the US) approved evolocumab (Repatha) July 21, 2015 in Europe. This new class (family) of medicines offers great hope for treating abnormal cholesterol. Prescribers in Europe may soon be able to be use Repatha for:
1) Treating adult patients who have a kind of cholesterol problem known as primary hypercholesterolemia (Heterozygous familial and non-familial HeFH or mixed dyslipidemia in addition to dietary steps. In these patients, Repatha can be used:
Alone or in combination with other lipid-lowering treatments when they don’t tolerate an earlier approved family of medicines known as statins (HMG-CoA reductase inhibitors such as Lipitor [atorvastatin] or rosuvastatin [Crestor]. This is a novel approach for such statin-intolerant people. Repatha will also be able to be used in patients who should not be given a statin (those for whom a statin is contraindicated).
In combination with a statin or statin combined with other lipid-lowering therapies in people who do not reach their LDL cholesterol goals with the maximum tolerated dose of a statin, OR
2) Treating of adults or adolescents who are 12 years old or older who have homozygous familial hypercholesterolemia (HoFH) in combination with other lipid-lowering therapies.
While this discussion is somewhat complicated, several Repatha Essentials emerge in this exciting new topic:
In Europe, current therapies (statins and other approved lipid-lowering medicines) fail to adequately lower bad cholesterol (LDL-C) over 60% of the time in high risk patients.
In very high risk patients, previously available treatments failed more than 80% of the time to lower bad cholesterol enough.
Repatha is the first PCSK9 inhibitor to be approved anywhere in the world.
Problems from Repatha (adverse event or AE profile) was similar overall to the placebo (control) groups of patients. The most common Adverse Reactions (ARs) more than or equal to 2% were nausea, flu (influenza)joint or back pain, upper respiratory tract infection or nose or throat soreness (nasopharyngitis). Most new medicines are studied after approval have results based on approval studies and reports are submitted which show more about potential problems as time goes on. The FOURIER study below will undoubtedly tell more about additional benefits from Repatha treatment and while not expected, will reveal any problems not seen in the approval studies.
The cost of cardiovascular disease (CVD) in the European Union (EU) is immense and totals roughly 106 billion Euros each year.
While Repatha may be reasonably expected (based on the ability to lower LDL cholesterol and thinking toward parallel results from the statin family of medicines) to decrease problems from and death from heart disease (cardiovascular morbidity and mortality), this is still unknown. There is a large study (clinical trial) called FOURIER- Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) which should let us know that answer. This is a 22 500-patient trial comparing evolocumab to statin treatment to see how it compares in:
1) Lowering
1) cardiovascular death
2) heart attack (MI)
2) Lowering hospitalization for unstable angina, stroke, or coronary revascularization.
The full results from FOURIER won't be available until 2018 at the earliest.
Because evolocumab (Repatha) is the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in the world, I will most likely create a profile for the new Essential Guide to Prescription Drugs, using Repatha as the representatve member of this impressive new family. Once the results of the FOURIER study are known, I may opt to include it in the True Breakthroughs in Medicines section.

全球首个PCSK9抑制剂--被美国FDA批准的新型降胆固醇REPATHA用于高胆固醇治疗
2015年8月27日，美国食品与药物管理局FDA批准了注射型药物Evolocumab（Repatha），用于目前其他治疗不能有效降低低密度脂蛋白胆固醇（LDL-C）水平的患者。
Evolocumab是PCSK9抑制剂类的第二个药物。FDA批准其用于以下情况：目前治疗不能有效降低LDL-C水平的杂合子型家族性高胆固醇血症（HeFH）或纯合子型家族性高胆固醇血症（HoFH）患者，或动脉脉粥样硬化性心血管病成人患者，在饮食控制和最大耐受剂量他汀的基础上，可联合应用Evolocumab。
Evolocumab是一种以特殊蛋白PCSK9为靶向的抗体，PCSK9可减少存在于肝脏中的可清除血液中LDL-C受体数量，通过阻碍PCSK9作用，可保证血液中存在更多受体，以减少LDL-C。
针对Evolocumab有效性与安全性的评估，主要来自一项52周的安慰剂对照试验，以及8项12周的安慰剂对照试验。其中，有两项试验特别纳入了HeFH患者，另一项试验特别纳入了HoFH患者。
在一项为期12周的试验中，纳入了329例他汀和其他降脂治疗不能有效降低LDL-C的HeFH患者，患者被随机分入Evolocumab组或安慰剂组，治疗持续12周。结果发现，Evolocumab组较安慰剂组的LDL-C水平降低60%。
Evolocumab最常见的副作用包括鼻咽炎、上呼吸道感染、流感、背痛，以及注射部位反应，如发红、疼痛或淤青。过敏反应，如麻疹等也有报告。应用药物时，出现严重过敏反应者，应立即停药并就诊。