FDA Makes Landmark Approval for ANGPTL-3 Inhibitors

FDA批准ANGPTL-3抑制剂具有里程碑意义

2021-02-12 07:30:13 BioSpace

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The U.S. Food and Drug Administration (FDA) approved Regeneron’s monoclonal antibody Evkeeza (evinacumab-dgnb) as an add-on treatment for adult and pediatric patients ages 12 and above with homozygous familial hypercholesterolemia (HoFH). The approval marks the first ANGPTL-3 Inhibitor to be greenlit by the FDA. Patients with Homozygous FH suffer from dangerously high levels of LDL-C, the “bad” cholesterol. Evkeeza was approved as an adjunct therapy alongside other low-density lipoprotein cholesterol (LDL-C) lowering therapies. As an angiopoietin-like protein 3 inhibitor, Evkeeza plays a central role in lipoprotein metabolism and blocks of lipoprotein lipase and endothelial lipase. The FDA’s approval of Evkeeza was based on pivotal results from the Phase III ELIPSE trial that demonstrated treatment with Evkeeza nearly halved cholesterol levels after 24 weeks of treatment in patients with HoFH, an ultra-rare inherited disease. Reductions in LDL-C seen with Evkeeza were observed as early as the second week of treatment and were maintained throughout the double-blind treatment period of 24 weeks, Regeneron said. Those results continued to be seen through the open label trial period of 48 weeks, the company added. The approval was granted under Priority Review. Evkeeza won Breakthrough Therapy Designation from the FDA in 2017 for HoFH. Homozygous familial hypercholesterolemia affects approximately 1,300 patients in the U.S. The disease occurs when two copies of the familial hypercholesterolemia (FH)-causing genes are inherited, one from each parent. This results in dangerously high levels of LDL-C. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years. George Yancopoulos, president and chief scientific officer of Tarrytown, N.Y.-based Regeneron, said the approval of Evkeeza is the latest example of the promise of Regeneron's development approach that harnesses genetic insights and pioneering technology to deliver new treatment options for patients. He said the company is proud to bring Evkeeza to patients with HoFH. Evkeeza is administered based on weight (15 mg per kilogram) once a month via intravenous infusion. The average wholesale cost per U.S. patient will vary based on weight, and is expected to be approximately $450,000 per year on average.  Evkeeza was invented using Regeneron's VelocImmune technology, which was also used to create Dupixent, Libtayo, Praluent, Kevzara and other branded drugs. Katherine A. Wilemon, founder and Chief Executive Officer of the FH Foundation, called the approval of Evkeeza a watershed moment for HoFH patients. "Those living with HoFH have faced devastatingly high LDL-C levels and an uncertain future. Evkeeza significantly lowered LDL-C levels in clinical trials and this new treatment offers an important new option for people living with HoFH,” Wilemon said in a statement. Daniel J. Rader, chairman of the Department of Genetics in the Perelman School of Medicine of the University of Pennsylvania and a leading HoFH expert who was involved with Evkeeza clinical trials, called Evkeeza a potentially transformational new treatment. “Existing therapies for HoFH are insufficient for the majority of patients. Evkeeza, through its unique mechanism of action, was shown to reduce LDL-C levels in patients with all forms of HoFH, even those with nearly no LDL receptor activity, and represents a highly meaningful improvement in our ability to control LDL-C levels in patients with HoFH,” Rader said. The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The effect of Evkeeza on cardiovascular morbidity and mortality has not been determined.  Most Read Today
美国食品和药物管理局(FDA)批准Regeneron公司的单克隆抗体Evkeeza(evinacumab-dgnb)作为一种附加疗法,用于12岁及以上的纯合子家族性高胆固醇血症(HoFH)的成人和儿童患者。该批准标志着第一个ANGPTL-3抑制剂被FDA批准。 纯合子型FH患者的低密度脂蛋白胆固醇(一种“坏”胆固醇)水平高得很危险。Evkeeza被批准作为与其他低密度脂蛋白胆固醇(LDL-C)降低疗法并列的辅助疗法。作为一种血管生成素样蛋白3抑制剂,Evkeeza在脂蛋白代谢和阻断脂蛋白脂肪酶和内皮脂肪酶中起着核心作用。 FDA批准Evkeeza是基于III期ELIPSE试验的关键结果,该试验表明,Evkeeza治疗HoFH患者24周后,胆固醇水平几乎减半,这是一种超罕见的遗传性疾病。Regeneron说,Evkeeza治疗的低密度脂蛋白胆固醇的降低早在治疗的第二周就被观察到,并且在24周的双盲治疗期间保持不变。该公司补充说,通过48周的开放标签试验期,这些结果继续可见。 批准是在优先审查下批准的。Evkeeza于2017年获得FDA关于HOFH的突破性疗法指定。 在美国,纯合子家族性高胆固醇血症患者约有1300人,当家族性高胆固醇血症(FH)基因的两个拷贝从父母各遗传一个时,这种疾病就会发生。这会导致危险的高水平LDL-C。HoFH患者早在青少年时期就有发生过早动脉粥样硬化疾病和心脏事件的风险。 总部位于纽约州塔里敦的Regeneron公司总裁兼首席科学官George Yancopoulos说,Evkeeza的批准是Regeneron公司利用基因洞察力和开创性技术为患者提供新治疗选择的开发方法前景的最新例证。他说,公司很自豪能为HOFH患者带来Evkeeza。 Evkeeza根据体重(每千克15毫克)通过静脉输注每月一次。每个美国患者的平均批发成本将根据体重而不同,预计平均每年约为450,000美元。 Evkeeza是利用Regeneron公司的VelocImmune技术发明的,该技术还被用于制造Dupixent、Libtayo、Praluent、Kevzara和其他品牌药物。 FH基金会创始人兼首席执行官Katherine a.Wilemon称Evkeeza的批准是HoFH患者的分水岭时刻。 Wilemon在一份声明中说:“HoFH患者面临着极高的LDL-C水平和不确定的未来。Evkeeza在临床试验中显著降低了LDL-C水平,这种新的治疗方法为HoFH患者提供了一个重要的新选择。” Daniel J.Rader是宾夕法尼亚大学Perelman医学院遗传学系主任,也是参与Evkeeza临床试验的主要HoFH专家,他称Evkeeza是一种具有潜在变革性的新疗法。 “现有的治疗HoFH的方法对大多数患者来说是不够的。Evkeeza通过其独特的作用机制,被证明可以降低所有形式的HoFH患者的LDL-C水平,甚至那些几乎没有LDL受体活性的患者,这代表了我们控制HoFH患者LDL-C水平的能力的一个非常有意义的改进,“Rader说。 Evkeeza的安全性和有效性尚未在其他原因引起的高胆固醇血症患者中建立,包括杂合子家族性高胆固醇血症(HeFH)患者。Evkeeza对心血管发病率和死亡率的影响尚未确定。 今天阅读最多的

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