2019年5月7日，FDA批准amifampridine（商品名：Ruzurgi，JacobusPharmaceutical公司开发）片上市，用于治疗6~17岁的Lambert-Eaton肌无力综合征（LEMS）儿科患者。
这是FDA批准的第一款针对LEMS儿科患者的新药。Ruzurgi曾获得过FDA授予的优先审评、快速通道以及孤儿药资格。2018年11月28日，Ruzurgi获批用于治疗LEMS成人患者
FDA药物评价与研究中心神经病学产品部主任Billy Dunn博士说：“我们将继续促进罕见病治疗的开发和批准，尤其是儿科治疗。这一批准为LEMS儿科患者提供了急需的治疗选择，这些患者往往因为肌无力和疲惫而影响到日常生活。”
一般信息
amifampridine（商品名：Ruzurgi）片是一种钾通道阻滞剂。
amifampridine（商品名：Ruzurgi）片特别适用于治疗6岁至17岁以下患者的Lambert-Eaton肌无力综合征（LEMS）。
Ruzurgi作为口服片剂提供。推荐剂量如下：
患者6至17岁以下，体重45公斤以上：
初始剂量为每日15至30毫克，分剂量。每日增加5至10毫克增量，每日最多5剂
最大单剂量为30毫克;每日最大剂量为100毫克
患者6至不到17岁，体重不足45公斤：
初始剂量为每日7.5至15毫克，分剂量。每日增加2.5毫克至5毫克增量，每日最多5剂
最大单剂量为15毫克;每日最大剂量为50毫克。
临床结果
FDA批准
美国食品和药物管理局批准Ruzurgi是基于对32名成年患者的随机，双盲，安慰剂对照戒断研究，其中患者在进入研究之前服用Ruzurgi至少三个月。
该研究比较了继续使用Ruzurgi的患者和转为安慰剂的患者。效力的主要衡量标准是，当3TUG的时间匹配平均值与3TUG的时间匹配平均值相比时，在停止使用活性药物时，三次计时和去试验（3TUG）的变化程度（例如，大于30％恶化）的分类基线评估。
3TUG衡量一个人从椅子上升，走3米，然后连续3次回到椅子上而没有停顿的时间。较高的3TUG分数代表更大的损伤。随机接受继续使用Ruzurgi的患者在最终给药后3TUG试验中没有经历超过30％的恶化。相比之下，安慰剂组中72％的患者在最终给药后3TUG试验中确实经历了大于30％的恶化。
副作用
与使用Ruzurgi相关的不利影响可能包括但不限于以下内容：
灼热感或刺痛感（感觉异常）
腹痛
消化不良
头晕
恶心
在没有癫痫病史的患者中观察到癫痫发作。
作用机制
amifampridine（商品名：Ruzurgi）片是一种钾通道阻滞剂。Ruzurgi对LEMS患者发挥治疗作用的机制尚不完全清楚。
Ruzurgi Approved for Pediatric Patients With Lambert-Eaton Myasthenic Syndrome
The Food and Drug Administration (FDA) has approved Ruzurgi (amifampridine; Jacobus Pharmaceutical) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to <17 years of age.
Ruzurgi contains amifampridine, a broad spectrum potassium channel blocker. The mechanism by which amifampridine exerts its therapeutic effect in LEMS patients has not been fully elucidated.
The use of Ruzurgi for pediatric patients was based on evidence from clinical studies eva luating the treatment in adults. Data from these trials were used to identify a dosing regimen for younger patients. Amifampridine is marketed under the brand name Firdapse (Catalyst) for adult patients with LEMS.
The approval of Ruzurgi was based on data from a placebo-controlled withdrawal study conducted in 32 adult patients who were taking Ruzurgi for ≥3 months before entering the study; patients either continued on Ruzurgi or were switched to placebo. Results showed that those who continued with the treatment experienced less impairment based on a test that assessed the time it took to rise from a chair, walk 3 meters, and return to the chair 3 consecutive times without stopping.
In addition, compared with patients who continued treatment with Ruzurgi, those in the placebo group reported greater perceived weakening, according to scores derived from a self-assessment scale for LEMS-related weakness.
With regard to safety, the most common adverse reactions experienced by both pediatric and adult patients were paresthesia, abdominal pain, indigestion, dizziness, and nausea.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug eva luation and Research. |
