Olezarsen

6月25日，Ionis Pharmaceuticals宣布，FDA已经接受Olezarsen治疗家族性高乳糜微粒血症综合征（FCS）的新药上市申请（NDA），并授予其优先审查资格，PDUFA日期为2024年12月19日。 家族性乳糜微粒血症综合征是一种罕见的遗传性疾病，由脂蛋白酶（LPL）功能受损引起，其特征为甘油三酯水平极高。据统计，全球每百万人中有1-2人受到影响。除了疲劳、严重复发性腹痛等慢性健康问题外，FCS患者发生急性胰腺炎的风险也很高。 Olezarsen（IONIS-APOCIII-LRx）是一种新型N-乙酰半乳糖胺（GalNAc）结合的反义寡核苷酸，靶向肝脏APOC III mRNA，可以选择性地抑制APOC III的合成。而抑制APOC III的合成可能是降低甘油三酯水平的有效途径。 本次NDA主要基于III期Balance研究数据。Balance研究是一项全球、多中心、随机、双盲、安慰剂对照的III期临床试验，共招募了66例成人FCS患者，这些患者接受了包括他汀类药物、贝特类药物和omega-3脂肪酸等在内的背景治疗。在该研究中，患者1:1:1随机皮下注射50、80mg Olezarsen或者安慰剂，每4周1次，持续53周。主要终点是与安慰剂相比，6个月时治疗组患者空腹甘油三酯水平相较基线的百分比变化。次要终点包括12个月时的患者甘油三酯水平以及急性胰腺炎事件发生率。 结果显示，80mg剂量组中，Olezarsen达到了主要终点，6个月时经安慰剂调整后患者甘油三酯水平较基线有统计学意义降低（44%，p<0.001）；从6个月到12个月，患者甘油三酯水平持续降低，经安慰剂调整后降低了59%；apoC-III水平经安慰剂调整后在6个月、12个月时较基线分别减少74%、81%。 50mg剂量组中，Olezarsen也降低了甘油三酯水平，但6个月后与安慰剂相比并无统计学意义降低（22%，p=0.078）；从6个月到12个月，经安慰剂调整后甘油三酯水平减少44%。 此外，与安慰剂组（11次）相比，Olezarsen治疗的患者12个月期间急性胰腺炎事件明显减少，其中80mg、50mg剂量组都只发生过1次。安慰剂调整后，接受Olezarsen治疗的患者全因住院率较基线降低了84%。总体而言，Olezarsen安全性和耐受性良好。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。 精彩预告 线上直播 ↑点击扫码，直达直播间↑

– Olezarsen PDUFA date set for December 19, 2024 for treatment of familial chylomicronemia syndrome – – Phase 3 enrollment completed in CORE, CORE2 and ESSENCE evaluating olezarsen for the treatment of severe hypertriglyceridemia, with results expected in 2H 2025 – CARLSBAD, Calif., June 25, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for olezarsen, an investigational RNA-targeted medicine for the treatment of adults with familial chylomicronemia syndrome (FCS). The FDA has set an action date of December 19, 2024 and indicated they are not currently planning an advisory committee meeting for olezarsen. "FCS is a debilitating, rare, genetic disease that causes significant physical, emotional and financial burden with no approved treatment options in the U.S.," said Brett Monia, Ph.D., chief executive officer of Ionis. "The Priority Review underscores the urgent need people living with FCS have for a medicine that may help lower triglyceride levels and reduce incidence of life-threatening acute pancreatitis events. We look forward to partnering closely with the FDA during the review process as we work to bring this potentially breakthrough medicine to patients before the end of 2024. Separately, we are pleased with the progress of our now fully enrolled Phase 3 program investigating olezarsen in the much more common severe hypertriglyceridemia population." Priority Review is a designation for medicines that have the potential to provide significant improvements in the treatment, prevention or diagnosis of a serious disease, with the expectation of the FDA taking action within six months, compared to 10 months under standard review. The application to the FDA was based on positive results from Balance, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study. The study results were presented at the 2024 American College of Cardiology (ACC) Annual Meeting and published simultaneously in The New England Journal of Medicine (NEJM). The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023, as well as Orphan Drug designation and Breakthrough Therapy designation in February 2024. Ionis is planning additional regulatory filings for the treatment of FCS in the European Union this year. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in three Phase 3 clinical trials – CORE, CORE2 and ESSENCE, all three of which completed enrollment in the first half of 2024. CORE and CORE2 enrolled more than 1,000 sHTG patients with fasting triglyceride levels ≥500 mg/dL; ESSENCE enrolled more than 1,400 high triglyceride patients with fasting triglyceride levels ≥150 mg/dL to <500 mg/dL who were diagnosed and/or at risk for atherosclerotic cardiovascular disease as well as patients with fasting triglycerides ≥500 mg/dL. sHTG is a common, life-threatening condition that can result in severe health complications, including potentially fatal acute pancreatitis (AP). Data are expected in the second half of 2025. About Olezarsen Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG). Olezarsen is designed to lower the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. Olezarsen is an investigational medicine that has not been reviewed or approved for the treatment of any disease by any regulatory authority. About FCS FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact one to 13 people per million in the U.S. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and people with FCS are generally nonresponsive to standard triglyceride lowering therapies. People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to manage diets to navigate the health risks associated with FCS. About sHTG sHTG is a disease categorized by triglyceride levels of 500 mg/dL and above. It develops due to primary (genetic) and secondary causes including diet and lifestyle, other medical conditions and certain medications. More than three million people are currently estimated to live with sHTG in the U.S. People living with sHTG are at high risk of pancreatitis and damage to the pancreas, as such, reducing the risk of pancreatitis is a critically important reason to treat sHTG. People with sHTG are also at risk of heart, brain and blood vessel damage. There remains a need for additional therapeutic options for the treatment of sHTG. Endocrinology and cardiovascular treatment guidelines recommend treating triglyceride levels of ≥500 mg/dL to reduce the risk of pancreatitis. Multiple treatment guidelines recommend lifestyle interventions to reduce triglyceride levels in people with sHTG and the addition of a triglyceride lowering medicine such as a fibrate or omega-3 fatty acid if needed to reduce fasting triglycerides to appropriate levels. However, these interventions are not sufficient for all people with sHTG, for whom there remains a significant need for new treatments that may help further reduce triglyceride levels and the risk of pancreatitis. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis Forward-looking Statements This press release includes forward-looking statements regarding olezarsen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Ionis Investor Contact: D. Wade Walke, Ph.D. [email protected] 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc.