FDA批准首款XI因子抑制剂Sunharbo：试验中再次中风风险降低26%
华盛顿 — 美国食品药品管理局（FDA）11月9日批准 Sunharbo（asundexian）50 毫克片剂上市销售。这是美国批准的第一款活化 XI 因子（FXIa）抑制剂，与抗血小板治疗联用，用于降低成人近期发生轻至中度非心源性缺血性中风（血栓并非来自心脏的中风）或高风险短暂性脑缺血发作（TIA，俗称小中风）之后再次中风的风险。
FDA 药物评价与研究中心心脏病学、血液学、内分泌学与肾脏病学办公室主任 Hylton V. Joffe 说，中风是美国致残与致死的主要原因之一，幸存者面临再次中风的风险，这项批准为患者与医护人员在二级预防上提供了一个有意义的新选择。
这项批准依据三期临床试验 OCEANIC-STROKE 的结果。这项多中心、随机、双盲、安慰剂对照试验共纳入 12,327 名成人，受试者为近期发作的非心源性缺血性中风患者（美国国立卫生研究院卒中量表评分不高于 15 分）或高风险短暂性脑缺血发作患者，在症状出现 72 小时内随机分组，两组都同时接受抗血小板治疗。结果显示，每日一次服用 Sunharbo 50 毫克的一组，与安慰剂组相比，缺血性中风风险降低了 26%，中位治疗时长为 14.2 个月。
安全性方面，两组的大出血总体发生率相近，但 75 岁以上患者以及治疗最初 90 天内，Sunharbo 组的大出血有所增加，胃肠道出血也比安慰剂组更常见。Sunharbo 组最常见的不良反应是腹泻，发生率在 3% 以上。
FDA 同时明确了几项使用限制：Sunharbo 不与合并 P 糖蛋白和强 CYP3A4 诱导剂类药物（如卡马西平）同用，以免药效下降；中度或重度肝功能不全患者不建议使用；择期手术或有创操作前至少停药 24 小时，急性缺血性中风溶栓治疗后至少 24 小时内也不使用。该药未获批准用于房颤患者的卒中预防。
FDA 此前已授予 Sunharbo 快速通道与优先审评资格。本次批准的持有人为位于 New Jersey 州 Whippany 的 Bayer HealthCare Pharmaceuticals Inc.。据路透社报道，中国药品监管部门已于 10 月下旬先行批准该药在华上市。
（来源：美国食品药品管理局）
FDA Approves Sunharbo, First Factor XIa Inhibitor: Recurrent Stroke Risk Cut 26% in Trial
WASHINGTON — The U.S. Food and Drug Administration (FDA) on November 9 approved Sunharbo (asundexian) 50 mg tablets. It is the first factor XIa (FXIa) inhibitor approved in the United States, for use in combination with antiplatelet therapy to reduce the risk of stroke in adults following a recent mild-to-moderate non-cardioembolic ischemic stroke, a stroke caused by a clot that did not originate in the heart, or a high-risk transient ischemic attack (TIA), often called a mini-stroke.
"Stroke is a leading cause of disability and death in the United States, and survivors are at risk of having another stroke," said Hylton V. Joffe, M.D., MMSc, Director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology in the FDA's Center for Drug Evaluation and Research. "Today's approval represents a meaningful advance for patients and health care providers seeking a new option for secondary stroke prevention."
The approval was based on OCEANIC-STROKE, a multicenter, randomized, double-blind, placebo-controlled phase 3 study that enrolled 12,327 adults. Participants had a recent non-cardioembolic ischemic stroke (NIH Stroke Scale score of 15 or less) or a high-risk TIA and were randomly assigned to Sunharbo or placebo within 72 hours of symptom onset, with both groups also receiving antiplatelet therapy. Sunharbo 50 mg once daily significantly reduced the risk of ischemic stroke by 26% compared with placebo over a median treatment period of 14.2 months.
On safety, the overall rate of major bleeding was similar between the Sunharbo and placebo groups, but it was increased with Sunharbo in patients older than 75 years and during the first 90 days of treatment. Gastrointestinal bleeding occurred more commonly with Sunharbo than with placebo. The most frequently reported adverse reaction, occurring in 3% or more of Sunharbo-treated patients, was diarrhea.
The FDA also set out several limits on use. Concomitant use with medicines that are combined P-gp and strong CYP3A4 inducers, such as carbamazepine, is not recommended because they may decrease Sunharbo's effectiveness. Sunharbo is not recommended in patients with moderate or severe hepatic impairment. It should be withheld at least 24 hours before elective surgery or invasive procedures and for at least 24 hours after thrombolysis for acute ischemic stroke. Sunharbo is not approved for stroke prevention in patients with atrial fibrillation.
The FDA had granted Sunharbo Fast Track and Priority Review designations. The approval was granted to Bayer HealthCare Pharmaceuticals Inc. of Whippany, New Jersey. According to Reuters, China's drug regulator approved the drug late last month.
(Source: U.S. Food and Drug Administration)
来源：美国食品药品管理局
发布：GSM·美国（发布链接）
图片来源：图：美国食品药品管理局总部大楼（GSM 固定图库）。 / Photo: U.S. Food and Drug Administration headquarters (GSM asset library).
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