Nexletol（双歧酸）片

公司名称：Esperion Therapeutics，Inc.

批准日期：2020年2月21日

治疗：高胆固醇血症

Nexletol（苯丙二酸）是一流的三磷酸腺苷柠檬酸裂解酶（ACL）抑制剂，用于治疗患有杂合性家族性高胆固醇血症或已确立的动脉粥样硬化性心血管疾病的成人，这些患者需要进一步降低LDL-胆固醇。

密歇根州安那堡市，2020年2月21日（美国地球仪新闻）– Esperion（NASDAQ：ESPR）今天宣布，美国食品药品监督管理局（FDA）批准了口服，每日一次的Nexletol™（比美多酸）片剂，非他汀类药物（LDL-C）降低药物。 Nexletol被认为是饮食和最大耐受他汀类药物的辅助治疗，用于治疗杂合子家族性高胆固醇血症（HeFH）或已确立的动脉粥样硬化性心血管疾病（ASCVD）的成年人，需要进一步降低LDL-C。尚不确定Nexletol对心血管疾病的发病率和死亡率的影响。 Nexletol是自2002年以来批准的针对指定患者的第一种口服，每日一次，非他汀类降脂药物。

Nexletol是一流的ATP柠檬酸裂解酶（ACL）抑制剂，可通过抑制肝脏中的胆固醇合成来降低LDL-C。

Esperion总裁兼首席执行官蒂姆·梅勒本（Tim Mayleben）表示：“耐世泰尔已履行了我们对数百万患者的承诺，如果他们因胆固醇不良而患有ASCVD或HeFH，他们将寻求新的治疗选择。” “即使他汀类药物的耐受性达到最大，这可能意味着他汀类药物根本没有，但其中一些患者仍无法达到他们的LDL-C目标。今天的批准为他们提供了一种新药以及健康饮食。我们对所有对Esperion脂质专家团队充满信心的患者和医生表示由衷的感谢。”

LDL-C是体内发现的蜡状，脂肪状物质。升高的LDL-C有助于动脉中这种脂肪的堆积，并可能导致心血管事件，包括心脏病和中风。尽管有包括他汀类药物治疗在内的标准治疗方法，但据估计在美国有近1500万患者（约四分之一）无法达到指导性推荐的LDL-C水平。

Esperion第三阶段执行委员会主席兼教授兼首席科学家Christie M. Ballantyne医师表示：“ FDA批准Nexletol为因HeFH而导致LDL-C和ASCVD升高或心血管疾病风险增加的患者提供了重要选择。”休斯敦贝勒医学院心脏病学系。 “尽管有可用药物，仍有数百万患者无法达到他们的LDL-C目标。 Nexletol是近二十年来针对指定患者的第一个口服，每日一次，非他汀类药物治疗选择。”

Nexletol的批准得到全球关键的3期LDL-C降低计划的支持，该计划在3,000多名患者中进行。在这些研究中，当与中度或高强度他汀类药物一起使用时，奈塞特洛平均提供18％的安慰剂校正LDL-C降低。第三阶段开发计划的结果已发表在《新英格兰医学杂志》（040研究）和《美国医学协会杂志》（047研究）中。

Nexletol在临床研究中通常耐受良好。标签警告和注意事项包括高尿酸血症，一小部分患者会出现痛风，以及肌腱破裂或受伤的风险增加。总的来说，在3期研究中，接受奈克塞特的患者中最常报告的不良事件在接受安慰剂的患者中也以相似的比率报告。 Nexletol报告的最常见不良事件（发生率≥2％，大于安慰剂）是上呼吸道感染，肌肉痉挛，高尿酸血症，背部疼痛，腹痛或不适，支气管炎，四肢疼痛，贫血和肝酶升高。 Nexletol报道的大多数不良事件的严重程度为轻度至中度，并且在接受安慰剂的患者中与不良事件的发生相平衡。有关Nexletol的其他信息，请访问Esperion.com上的“完整处方信息”。

今天的批准强调了Esperion的承诺，即向患有ASCVD或HeFH且无法达到最大耐受他汀类药物的LDL-C目标的成年患者提供Nexletol。 Esperion正在与健康保险提供商合作，以确保广泛的保险范围和患者对Nexletol的使用。符合条件的患者可在Nexletol的商业药物保险范围内每次支付10美元，最多三个月。此外，Esperion致力于为Medicare患者实现最低的品牌等级覆盖率。 Esperion将为医师推荐使用Nexletol治疗的患者提供资源。这些资源包括教育材料，专门的呼叫中心以及针对符合条件的患者的自付费用计划。

Nexletol将于2020年3月30日在美国通过处方销售。

Esperion的第二种降低LDL-C的药物，苯二酸/依泽替米贝组合片剂，目前正在接受美国FDA的审查； PDUFA的目标日期是2020年2月26日。

Nexletol（双歧酸）片

Nexletol是一流的ATP柠檬酸裂解酶（ACL）抑制剂，可通过减少胆固醇的生物合成和上调LDL受体来降低LDL-C。在3,000多名患者中完成的3期研究完成了，超过2,000例患者接受了Nexletol治疗，结果表明，在中度或高强度他汀类药物患者中使用安慰剂后，平均LDL-C降低了18％。 Nexletol是近20年以来在美国批准的针对ASCVD或HeFH患者的首款口服，每日一次，非他汀类降脂药物LDL-C。 Nexletol于2020年2月获得FDA批准。

使用指示和限制

Nexletol被认为是饮食和最大耐受他汀类药物的辅助治疗，用于治疗需要进一步降低LDL-C的杂合性家族性高胆固醇血症或已确立的动脉粥样硬化性心血管疾病的成年人。尚不确定Nexletol对心血管疾病的发病率和死亡率的影响。

重要安全信息

警告和注意事项：

•血清尿酸升高。根据临床指示定期评估尿酸水平。监测高尿酸血症的体征和症状，并酌情开始使用降低尿酸的药物进行治疗。既往有痛风病史的患者，使用奈克泰尔痛风的风险更高，尽管在没有痛风史的奈克唑醇治疗的患者中，痛风的发生率也比安慰剂高。

•肌腱破裂。在肌腱断裂的第一个迹象时停止使用Nexletol。有肌腱疾病或肌腱破裂病史的患者应避免使用奈克酚。

不良反应：

•最常见的不良反应（发生率≥2％，大于安慰剂）是上呼吸道感染，肌肉痉挛，高尿酸血症，背部疼痛，腹痛或不适，支气管炎，四肢疼痛，贫血和肝酶升高。

药物相互作用：

•避免与辛伐他汀大于20 mg的奈克塞特同时使用。

•避免将Nexletol与超过40 mg的普伐他汀同时使用。

鼓励您向FDA报告处方药的不良副作用。请访问www.fda.gov/medwatch或致电1-800-FDA-1088，或致电833-377-7633（833 ESPRMED）向Esperion报告副作用。

清除心血管结局试验

尚不确定Nexletol对心血管疾病的发病率和死亡率的影响。 Esperion发起了一项全球心血管疾病预后试验（CVOT），以评估耐克沙特对仅能耐受低于每日最低批准剂量的心血管疾病患者（CVD）或处于高风险中的重大心血管事件发生的影响他汀类药物的起始剂量，被视为“他汀类药物厌恶”。 CVOT（称为CLEAR心血管预后试验）是一项事件驱动，全球性，随机，双盲，安慰剂对照研究，于2019年8月在32个国家/地区的1,400多个地点完成了14032例高胆固醇血症和高CVD风险患者的纳入研究。

太空疗法

通过卓越的科学和临床知识，以及对胆固醇生物学的深刻理解，Esperion经验丰富的脂质管理团队致力于开发新的降低LDL-C的药物，这些药物将对减少全球心血管疾病（对心血管疾病造成死亡的主要原因）产生重大影响世界。有关更多信息，请访问www.esperion.com并在Twitter上关注我们，网址为www.twitter.com/EsperionInc

Esperion Therapeutics对高脂血症患者的承诺

高水平的LDL-C会导致脂肪和胆固醇在动脉壁内和动脉壁上积聚（称为动脉粥样硬化），可能导致心血管事件，包括心脏病发作或中风。在美国，有9600万人，即成年人口的37％以上，其LDL-C升高。在美国，尽管采取了最大耐受性的调脂疗法（包括被认为是他汀类药物不受欢迎的个体），但仍有大约1800万人患有LDL-C水平升高的动脉粥样硬化性心血管疾病（ASCVD）或杂合子家族性高胆固醇血症（HeFH）。心血管事件的风险1。在美国，仅使用他汀类药物无法达到LDL-C的ASCVD患者中，超过50％的患者需要降低不到40％才能达到其LDL-C阈值2。

Esperion作为脂质管理公司的使命是提供口服，每日一次的药物，以补充现有的口服药物，以提供这些患者所需的额外LDL-C降低。

Company: Esperion Therapeutics, Inc.
Date of Approval: February 21, 2020
Treatment for: Hypercholesterolemia

Nexletol (bempedoic acid) is a first-in-class, adenosine triphosphate-citrate lyase (ACL) inhibitor for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-Cholesterol.

ANN ARBOR, Mich., Feb. 21, 2020 (GLOBE NEWSWIRE) -- Esperion (NASDAQ:ESPR) announced today that the U.S. Food and Drug Administration (FDA) approved Nexletol™ (bempedoic acid) tablet, an oral, once-daily, non-statin  (LDL-C) lowering medicine. Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-C. The effect of Nexletol on cardiovascular morbidity and mortality has not been determined. Nexletol is the first oral, once-daily, non-statin LDL-C lowering medicine approved since 2002 for indicated patients.

Nexletol is a first-in-class ATP Citrate Lyase (ACL) inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in the liver.

“Nexletol delivers upon a commitment we’ve made to millions of patients for a new treatment alternative if they struggle with bad cholesterol and have ASCVD or HeFH,” said Tim Mayleben, president and chief executive officer of Esperion. “Even with maximally tolerated statins, which may mean no statin at all, some of these patients can’t achieve their LDL-C goals. Today’s approval provides them with a new medicine to go along with a healthy diet. We express our sincere gratitude to all of the patients and physicians who put their confidence in Esperion’s team of lipid experts.”

LDL-C is a waxy, fat-like substance that’s found in the body. Elevated LDL-C contributes to a buildup of this fat in the arteries and can lead to cardiovascular events including heart attack and stroke. Despite standard of care treatments, including statin therapy, it is estimated nearly 15 million patients (approximately one in four patients) in the U.S. cannot achieve guideline recommended LDL-C levels.

“The FDA approval of Nexletol provides an important option for patients living with elevated LDL-C and ASCVD or increased risk for cardiovascular disease because of HeFH,” said Christie M. Ballantyne, M.D., chairman of Esperion’s Phase 3 Executive Committee and professor and chief of cardiology at Baylor College of Medicine in Houston. “There are millions of patients who are unable to reach their LDL-C targets despite available medicines. Nexletol is the first oral, once-daily, non-statin treatment option for indicated patients in nearly two decades.”

The approval of Nexletol is supported by a global pivotal Phase 3 LDL-C lowering program conducted in more than 3,000 patients. In these studies, Nexletol provided an average of 18 percent placebo corrected LDL-C lowering when used with moderate or high intensity statins. Results from the Phase 3 development program have been published in The New England Journal of Medicine (040 Study), and The Journal of the American Medical Association (047 Study).

Nexletol was generally well-tolerated in clinical studies. Label warnings and precautions include hyperuricemia, with the development of gout in a small percentage of patients, as well as increased risk of tendon rupture or injury. Overall in Phase 3 studies, the adverse events reported most frequently in patients who received Nexletol were generally reported at similar rates in patients who received placebo. The most common adverse events reported with Nexletol (incidence ≥ 2% and greater than placebo) were upper respiratory tract infections, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. The majority of adverse events reported with Nexletol were mild to moderate in severity and balanced in occurrence with adverse events in patients receiving placebo. For additional information on Nexletol, please see Full Prescribing Information at Esperion.com.

Today’s approval underscores Esperion’s commitment to deliver Nexletol to adult patients suffering from ASCVD or HeFH and who are unable to reach their LDL-C goal on maximally tolerated statins. Esperion is working with health insurance providers to help ensure broad insurance coverage and patient access to Nexletol. Eligible patients with commercial drug insurance coverage for Nexletol may pay as little as $10 per fill, up to a 3-month supply. Additionally, Esperion is committed to achieving the lowest branded tier coverage for Medicare patients. Esperion will provide resources to patients whose physician recommends treatment with Nexletol. These resources include educational materials, a dedicated call center, as well as a co-pay program for eligible patients.

Nexletol will be commercially available in the U.S., by prescription only, on March 30, 2020.

Esperion’s second LDL-C lowering medicine, the bempedoic acid / ezetimibe combination tablet, is currently under review by the U.S. FDA; the PDUFA goal date is February 26, 2020.

Nexletol (bempedoic acid) Tablet

Nexletol is a first-in-class ATP Citrate Lyase (ACL) inhibitor that lowers LDL-C by reducing cholesterol biosynthesis and up-regulating the LDL receptors. Completed Phase 3 studies conducted in more than 3,000 patients, with over 2,000 patients treated with Nexletol, demonstrated an average 18 percent placebo corrected LDL-C lowering when used in patients on moderate or high-intensity statins. Nexletol is the first oral, once-daily, non-statin LDL-C lowering medicine approved in the U.S. in nearly 20 years for patients with ASCVD or HeFH. Nexletol was approved by the FDA in February 2020.

Indication and Limitation of Use
Nexletol is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. The effect of Nexletol on cardiovascular morbidity and mortality has not been determined.

Important Safety Information

Warnings and Precautions:

· Elevations in serum uric acid have occurred. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate. The risk for gout events with Nexletol was higher in patients with a prior history of gout although gout also occurred more frequently than placebo in patients treated with Nexletol who had no prior gout history.

· Tendon rupture has occurred. Discontinue Nexletol at the first sign of tendon rupture. Avoid Nexletol in patients who have a history of tendon disorders or tendon rupture.

Adverse Reactions:

· The most common (incidence ≥ 2% and greater than placebo) adverse reactions are upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia and elevated liver enzymes.

Drug Interactions:

· Avoid concomitant use of Nexletol with simvastatin greater than 20 mg.

· Avoid concomitant use of Nexletol with pravastatin greater than 40 mg.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 or report side effects to Esperion at 833-377-7633 (833 ESPRMED).

CLEAR Cardiovascular Outcomes Trial

The effect of Nexletol on cardiovascular morbidity and mortality has not been determined. Esperion initiated a global cardiovascular outcomes trial (CVOT) to assess the effects of Nexletol on the occurrence of major cardiovascular events in patients with, or at high risk for, cardiovascular disease (CVD) who are only able to tolerate less than the lowest approved daily starting dose of a statin and are considered "statin averse." The CVOT — known as CLEAR Cardiovascular Outcomes Trial — is an event-driven, global, randomized, double-blind, placebo-controlled study that completed enrollment in August 2019 of 14,032 patients with hypercholesterolemia and high CVD risk at over 1,400 sites in 32 countries.

Esperion Therapeutics

Through scientific and clinical excellence, and a deep understanding of cholesterol biology, the experienced Lipid Management Team at Esperion is committed to developing new LDL-C lowering medicines that will make a substantial impact on reducing global cardiovascular disease, the leading cause of death around the world. For more information, please visit www.esperion.com and follow us on Twitter at www.twitter.com/EsperionInc

Esperion Therapeutics’ Commitment to Patients with Hyperlipidemia

High levels of LDL-C can lead to a build-up of fat and cholesterol in and on artery walls (known as atherosclerosis), potentially leading to cardiovascular events, including heart attack or stroke. In the U.S., 96 million people, or more than 37 percent of the adult population, have elevated LDL-C. There are approximately 18 million people in the U.S. with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) living with elevated levels of LDL-C despite taking maximally tolerated lipid-modifying therapy — including individuals considered statin averse — leaving them at high risk for cardiovascular events1. In the United States, more than 50 percent of ASCVD patients who are not able to reach their LDL-C with statins alone need less than a 40 percent reduction to reach their LDL-C threshold2.

Esperion's mission as the Lipid Management Company is to deliver oral, once-daily medicines that complement existing oral drugs to provide the additional LDL-C lowering that these patients need.

Forward-Looking Statements

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the regulatory approval pathway for bempedoic acid tablet and the bempedoic acid / ezetimibe fixed dose combination tablet, the therapeutic potential of, and the clinical development plan for bempedoic acid tablet and the bempedoic acid / ezetimibe fixed dose combination tablet, including Esperion's timing, designs, plans for announcement of results regarding its CLEAR Outcomes study and other ongoing clinical studies for bempedoic acid tablet and the bempedoic acid / ezetimibe combination fixed dose tablet, timing for the review and approval of the NDAs and the MAAs, and Esperion's expectations for the market for medicines to lower LDL-C, including the commercial launch and market adoption of bempedoic acid tablet and the bempedoic acid / ezetimibe fixed dose combination tablet, if approved. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Esperion's actual results to differ significantly from those projected, including, without limitation, delays or failures in Esperion’s studies, that positive results from a clinical study of bempedoic acid may not be sufficient for EMA approval or necessarily be predictive of the results of future or ongoing clinical studies, that notwithstanding the completion of Esperion’s Phase 3 clinical development program for LDL-C lowering, the FDA or EMA require additional development in connection with seeking regulatory approval, or approval of an expanded indication, that existing cash resources may be used more quickly than anticipated, and the risks detailed in Esperion's filings with the Securities and Exchange Commission. Esperion disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

References
(1) Esperion market research on file: research project interviewing 350 physicians. Esperion Therapeutics, Inc. Sept-Oct 2018.
(2) Data on file: analysis of NHANES database. Esperion Therapeutics, Inc. 2018.

Source: Esperion Therapeutics

Posted: February 2020