Tonlamarsen

正文共： 3292字 8图预计阅读时间： 8分钟「  收集周期：8月8日-8月13日，包括“首次申请临床”及“首次申请上市”的化药、生物药、中药 」NDA汇总1、珂罗利单抗8月10日， CDE官网公示，罗氏的珂罗利单抗注射液（Crovalimab）的上市申请已获得受理，并被纳入优先审批品种，拟用于治疗目前未接受补体抑制剂治疗的成人和青少年（≥12岁）患者阵发性睡眠性血红蛋白尿症。Crovalimab是一种通过连续单克隆抗体回收技术（Smart-Ig）工程化改造的新一代C5抑制剂，可以阻断补体C5裂解为C5a和C5b，有望抑制补体活化。2022年5月，罗氏宣布Crovalimab在用于治疗阵发性睡眠性血红蛋白尿症（PNH）患者的III期临床研究COMMODORE 3中取得阳性结果，以乳酸脱氢酶（LDH）水平测定的溶血控制的平均比例，以及避免输血（TA）的患者比例均达到共同主要终点。PNH是一种由于体细胞xp22.1上PIG-A基因突变导致补体系统失调的罕见获得性造血干细胞克隆性疾病，临床表现以血管内溶血性贫血为主，可伴有血栓、肾功能不全、肺动脉高压等症状。除了骨髓移植，PNH尚无其他有效治愈手段，控制溶血发作是临床上治疗该病的主要手段，主要治疗药物包括糖皮质激素、免疫抑制剂、补体通路抑制剂等，其中抗补体C5药物是其当前标准疗法。IND汇总1、HLX608月9日，CDE官网显示，复宏汉霖的HLX60临床试验申请获受理，用于治疗实体瘤。HLX60是国内首款申报临床的GARP单抗，旨在靶向抑制调节性T（Treg）细胞产生具有免疫抑制效应的活性TGF-β发挥治疗作用。Treg的免疫抑制机制主要通过产生多种抑制性细胞因子，包括转化生长因子β（TGF-β）、IL-35和IL-10等。GARP单抗可以通过靶向抑制Treg细胞产生具有免疫抑制效应的活性转化生长因子β（TGF-β）发挥治疗作用。2、rAAV2/8-hCYP4V28月9日，上海天泽云泰生物（简称“天泽云泰”）宣布其自主研发的VGR-R01注射剂（rAAV2/8-CYP4V2）的IND申请获得CDE受理。VGR-R01是天泽云泰自主研发的针对CYP4V2基因突变导致的结晶样视网膜变性（BCD）患者的基因治疗产品，也是全球范围内首个申请新药临床试验的针对BCD的治疗性药物，作用原理为基因替代。BCD又称Bietti结晶样视网膜病变，是一种常染色体隐性遗传的进展性视网膜变性疾病。大多数BCD患者于20-40岁发病，出现夜盲和视力下降等症状，在50-60岁发展为法定盲人，目前暂无药物医治。3、CUD0028月9日，CDE官网公示，四川康德赛（简称“康德赛”）自主研发用于治疗晚期卵巢癌的个体化树突状细胞（DC）CUD002注射液临床试验的申请已受理。CUD002为中国首款基于患者肿瘤新生抗原的mRNA编辑DC肿瘤疫苗， C细胞作为最为高效的抗原递呈细胞，可根据患者独特的突变信息定制设计并制造，激发患者自身免疫系统识别卵巢癌抗原，产生抗肿瘤免疫反应并杀伤肿瘤细胞，让当前无法从现有疗法获益的患者看到新的曙光。在攻克癌症的道路上，康德赛借助其自主研发的四大平台“生物信息分析平台“、”mRNA平台“、”CUNDE®细胞平台“及”体内药效评价平台“持续研发可供进一步转化的候选细胞药物，依托四大平台支持新一代DC肿瘤疫苗技术迭代更新。4、BEBT-5038月8日，CDE官网显示，广州必贝特BEBT-503胶囊的1类新药临床申请获CDE受理，适应症可能为糖尿病合并非酒精性脂肪性肝炎。BEBT-503是一种高活性泛PPAR激动剂，用于治疗糖尿病合并非酒精性脂肪性肝炎。BEBT-503是目前为止活性最高的新型泛PPAR激动剂，属于安全性高的Fibrate类化合物，有可能成为治疗糖尿病、控制高脂血症、阻止非酒精性脂肪性肝炎症和纤维化进程以及保护心脏功能的有效药物。NASH是一种严重的进行性NAFLD，由肝脏脂肪堆积引起，并伴有炎症、肝细胞损伤，在某些情况下还会造成肝脏瘢痕。在美国，大约有1700万患者(占全球成年人口的3-5%)，中国约有5000万患者，由于肥胖和2型糖尿病患病率的增加以及人口老龄化，预计这一数字在未来10-15年将显著增长。5、通降颗粒8月8日，健民药业提交了通降颗粒的临床申请。据悉，健民药业于2018年独家受让中国中医科学院西苑医院拥有的通降颗粒临床前研究材料及临床申报期间的所有技术秘密和专利，交易金额为1000万元。公司表示，通降颗粒开发完成后将填补国内治疗胃食管反流病中成药市场空白；同时，公司作为中成药生产企业，通降颗粒有利于补充公司特色中药品种，丰富公司产品线。每周概览：全球核酸药物研发进展1. Ionis在2022年Q2财报中详细披露了目前管线进展Ionis下阶段两个重磅药进展Eplontersen：Eplontersen在ATTRv-PN患者的3期NEURO-TTRansform研究的中期分析中达到了共同主要和关键次要终点；有望在今年下半年向美国食品和药物管理局（FDA）提交新药申请（NDA）。Tofersen：百健公司在欧洲治愈ALS网络（ENCALS）会议上报告了3期VALOR研究和正在进行的tofersen开放标签扩展研究的长期数据，显示SOD1-ALS患者的临床获益。百健公司报告说，tofersen的NDA被FDA接受并授予优先审查权，处方药使用费法案（PDUFA）的行动日期是2023年1月25日。Ionis晚期管道的推进计划Pelacarsen：诺华公司在3期Lp(a)HORIZON心血管结果研究中，对已患心血管疾病和Lp(a)升高的患者进行了pelacarsen的全面招募，预计在2025年获得数据。Olezarsen：对FCS患者进行的olezarsen3期BALANCE研究实现了全面入组，预计将在2023年获得数据。Ionis中期研究项目的推进计划Bepirovirsen：葛兰素史克在欧洲肝脏研究协会（EASL）的国际肝脏大会™上公布了慢性乙型肝炎患者的B-Clear 2b期研究的积极数据。基于这些结果，葛兰素史克公司计划在2023年上半年将bepirovirsen推进到3期单一疗法研究中。IONIS-FB-LRx：罗氏报告了IONIS-FB-LRx在免疫球蛋白A肾病（IgAN）患者中的2期研究的积极数据。基于这些结果，罗氏授权并计划将IONIS-FB-LRx推进到3期研究。Fesomersen：拜耳公司报告说，在对终末期肾病患者进行的2b期RE-THINc ESRD研究中，Fesomersen达到了主要终点。Fesomersen还证明了因子XI活性水平的大幅和统计学意义上的降低。IONIS-AGT-LRx：治疗耐药高血压患者的2b期研究实现了全面入组，预计在2022年下半年获得数据ION904：启动ION904的2期研究，这是IONIS-AGT-LRx在耐药性高血压患者中的后续药物。ION582：被FDA授予孤儿药称号和罕见儿科疾病称号，用于治疗Angelman综合症患者。2. Arcturus Therapeutics在2022年Q2财报中披露mRNA药物进展ARCT-810：ARCT-810是该公司针对OTC缺乏症的mRNA治疗候选药物，将在24名患有OTC缺乏症的青少年和成人中进行随机，双盲，安慰剂对照，嵌套单次和多次上升剂量2期研究的评估。参与研究中心已在预筛查中确定了数十名患者，目标是在年底前获得中期概念验证数据。关于Arcturus TherapeuticsArcturus Therapeutics Holdings 成立于2013年，是一家全球晚期临床mRNA药物和疫苗公司，其技术优势：（i）LUNAR®脂质介导递送，（ii）STARR™ mRNA技术（samRNA）和（iii）mRNA药物物质以及药物产品制造专业知识。Arcturus的技术可应用于多种类型的核酸药物，包括信使RNA， 小干扰RNA，再循环RNA，反义RNA，microRNA，DNA和基因编辑疗法。Arcturus的技术受到美国、欧洲、日本、中国和其他国家/地区颁发的专利和专利申请的保护。3. Apellis Pharmaceuticals 在2022年Q2财报中披露了EMPAVELI +siRNA药物研发进展EMPAVELI + 小干扰RNA（siRNA）：Apellis正在研究EMPAVELI和siRNA的组合，这可能有可能降低EMPAVELI的治疗频率。Apellis预计将在2023年上半年提交其siRNA的研究性新药（IND）申请。关于艾佩利斯Apellis Pharmaceuticals， Inc. 是一家全球生物制药公司，致力于利用勇敢的科学、创造力和同情心来提供改变生活的疗法。在补体方面，十五年磨一剑，是全球第一个也是唯一一个获批靶向的C3疗法的公司。公司正在推进这门科学在罕见病、视网膜疾病和神经系统疾病领域的应用。4. 华东医药拟3.96亿元控股华仁科技，加码小核酸药物布局 8月9日，华东医药披露公告称，公司全资子公司中美华东拟以增资和受让股份的方式，收购芜湖华仁科技有限公司（以下简称“华仁科技”）60%股权，合计出资不超过3.96亿元。公告显示，华仁科技以小核酸药物和诊断试剂用核苷原料为主要业务领域， 通过多年研发投入和技术积累，形成了较为丰富的产品库（约1500种），并具备较完备的独立研发能力，在小核酸药物用核苷原料领域及诊断试剂用核苷酸（dNTP）领域处于行业先进地位。华东医药方面表示，华仁科技的收购，将快速补充公司工业微生物核苷版块在上述领域的技术积累和客户资源，与工业微生物在核苷版块已有的研发和产业布局形成有效协同；美华高科、珲达生物已开发酶法、合成等多种上游核苷原料， 匹配单体需求并已形成百公斤级以上的商业化生产能力，有望进一步降低华仁科技核苷产品单位生产成本；同时，珲达生物的国际化能力，亦有望助推华仁科技打开国际市场，加速核苷版块发展，进一步提升公司工业微生物核苷业务的整体市场竞争力。版权声明/免责声明本文为授权转载文章，版权归拥有者。仅供感兴趣的个人谨慎参考，非商用，非医用、非投资用。欢迎朋友们批评指正！衷心感谢！文中图片、视频为授权正版作品，或来自微信公共图片库，或取自公司官网/网络根据CC0协议使用，版权归拥有者。任何问题，请与我们联系（电话：13651980212。微信：27674131。邮箱：contact@drugtimes.cn）。衷心感谢！推荐阅读“最贵药物”Zolgensma出现两名儿童死亡，基因疗法面临新挑战又一个首款！FDA加快批准Enhertu（DS-8201）治疗HER2突变非小细胞肺癌患者药企们的「过冬」策略，裁员不尽兴，他还要收租...Aβ假说“被锤”后，离开4年的默沙东又被勾回来，买了一个连靶点都不知道的产品...54亿美金，买！歇了不到3个月的辉瑞，又开始溢价收购了...104家中国新药企业扬帆出海！ADC赛道喜讯频传！科伦博泰势头赶超老大哥石药 | 药时代出海系列对话RNA靶向新兴企业施能康（SynerK）：从Alnylam公司APOLLO-B的成功看RNAi药物的研发提前4个月！FDA批准ADC药物Enhertu（DS-8201）用于治疗「HER2低表达」乳腺癌患者，市场有望扩大5倍！接连7款药物试验失败！新药研发既要有毅力，更要有「及时止损」的智慧万字长文：从理论到生产，一文读懂mRNA-LNP制剂技术药时代第111期直播笔记 | 欧美儿童药物开发相关的法规和指导原则2022上半年成绩单出炉！勃林格殷格翰保持稳健增长，夯实研发管线！点击这里，欢聚药时代！

Reported positive eplontersen ATTRv-PN data, on track to file NDA in H2:22 Tofersen NDA under priority review, PDUFA January 25, 2023 Completed enrollment in pelacarsen Lp(a) HORIZON and olezarsen BALANCE Phase 3 studies On track to achieve 2022 financial guidance Webcast today, August 9, 2022, at 11:30 a.m. Eastern Time CARLSBAD, Calif., Aug. 9, 2022 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today reported financial results for the second quarter of 2022 and recent business achievements. "Over the first half of this year, we moved significantly closer to delivering an abundance of new medicines to the market. We reported positive Phase 3 data from the NEURO-TTRansform study of eplontersen in patients with hereditary ATTR polyneuropathy and we are on track to file an NDA in the second half of this year. We were also pleased that the FDA accepted the NDA for tofersen and granted priority review, enabling tofersen to potentially be the first disease modifying treatment approved for a genetic form of ALS. These achievements mean eplontersen and tofersen could be our next marketed products as early as next year," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We also significantly advanced our late- and mid-stage pipeline. The pelacarsen Lp(a) HORIZON and olezarsen BALANCE Phase 3 studies recently completed enrollment. Additionally, we reported positive data from six mid-stage programs, positioning us to grow our rich Phase 3 pipeline to at least eight medicines across 10 indications. We are looking forward to continuing our positive momentum in the second half of this year by presenting Phase 3 eplontersen data at the International Symposium on Amyloidosis in September, filing our eplontersen NDA, and reporting data from several important programs. These upcoming catalysts, together with our recent achievements, position us well to drive increasing value for all stakeholders." Second Quarter 2022 Summary Financial Results On track to achieve 2022 financial guidance, based on the following second quarter results: $134 million in total revenues $195 million of operating expenses on a non-GAAP basis(1) and $220 million on a GAAP basis $80 million net loss on a non-GAAP basis(1) and $105 million on a GAAP basis $2.0 billion of cash and short-term investments "We had a strong first half with year-over-year revenue growth of more than 15 percent. We continued to generate revenue from multiple diverse sources, with just over half from our marketed products and the balance from our numerous advancing partnered medicines. Additionally, our financial results reflect our accelerating investments in our rich late-stage pipeline and in our commercial readiness activities for eplontersen, olezarsen and donidalorsen," said Elizabeth L. Hougen, chief financial officer of Ionis. "With $2 billion of cash and investments, we have the financial resources to achieve our goal of bringing transformational medicines to the market. These results for the first half of the year keep us on track to meet our 2022 financial guidance." Recent Marketed Products Highlights SPINRAZA®: the global market leader for the treatment of spinal muscular atrophy (SMA) patients of all ages $431 million in worldwide SPINRAZA sales in the second quarter Biogen reported new results from the RESPOND study of SPINRAZA, stating the results indicate there are residual unmet clinical needs in infants and toddlers with SMA who were previously treated with gene therapy Biogen reported final data from Part A of the ongoing, three-part DEVOTE study demonstrating that a higher dosing regimen of SPINRAZA leads to higher levels of the drug in the cerebrospinal fluid and is generally well-tolerated TEGSEDI® and WAYLIVRA®: important medicines approved for the treatment of patients with polyneuropathy caused by hereditary TTR amyloidosis (ATTRv-PN) and familial chylomicronemia syndrome (FCS), respectively Continued to expand into new markets in Europe and Latin America through Swedish Orphan Biovitrum AB (Sobi) and PTC Therapeutics, respectively Second Quarter 2022 and Recent Events Advancing Ionis' next two potential marketed products Reported eplontersen met the co-primary and key secondary endpoints in the interim analysis of the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN; on track to file the New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the second half of this year Biogen reported longer-term data from the Phase 3 VALOR study and ongoing open-label extension study of tofersen showing clinical benefit in patients with SOD1-ALS at the European Network to Cure ALS (ENCALS) meeting Biogen reported that an NDA for tofersen was accepted and granted priority review by the FDA with a Prescription Drug User Fee Act (PDUFA) action date of January 25, 2023 Advancing Ionis' late-stage pipeline Novartis achieved full enrollment in the Phase 3 Lp(a) HORIZON cardiovascular outcomes study of pelacarsen in patients with established cardiovascular disease and elevated Lp(a) with data expected in 2025 Achieved full enrollment in the Phase 3 BALANCE study of olezarsen in patients with FCS with data expected in 2023 Advancing Ionis' mid-stage pipeline GSK presented positive data from the Phase 2b B-Clear study of bepirovirsen in patients with chronic hepatitis B at the European Association for the Study of the Liver's (EASL) International Liver Congress™. Based on these results, GSK plans to advance bepirovirsen into a Phase 3 monotherapy study in the first half of 2023 Roche reported positive data from the Phase 2 study of IONIS-FB-LRx in patients with immunoglobulin A nephropathy (IgAN). Based on these results, Roche licensed and plans to advance IONIS-FB-LRx into a Phase 3 study Bayer reported fesomersen met the primary endpoint in the Phase 2b RE-THINc ESRD study in patients with end-stage renal disease. Fesomersen also demonstrated substantial and statistically significant reductions in Factor XI activity levels Achieved full enrollment in the Phase 2b study of IONIS-AGT-LRx in patients with treatment-resistant hypertension, with data expected in the second half of 2022 Initiated a Phase 2 study of ION904, a follow-on medicine to IONIS-AGT-LRx in patients with treatment-resistant hypertension Granted orphan drug designation and rare pediatric disease designation by the FDA for ION582 for the treatment of patients with Angelman syndrome 2022 Pipeline Milestones(2) Second Quarter 2022 Financial Results Revenue Ionis' revenue was comprised of the following (amounts in millions): The Company's revenue in the first half of 2022 increased more than 15 percent compared to the same period last year. The increase was driven by significant partner payments Ionis earned across multiple partnered programs, including $37 million from AstraZeneca for its share of the global Phase 3 development costs for eplontersen. Refer to the detailed table of costs and reimbursements for the eplontersen collaboration provided later in this release. The Company also earned $57 million from Biogen for advancing several neurology disease programs and $22 million from Roche for advancing IONIS-FB-LRx. Already in the third quarter of 2022, the Company has earned nearly $45 million from Roche and Biogen. The Company's commercial revenue in the first half of 2022 decreased 12 percent compared to the same period last year. SPINRAZA royalties decreased primarily due to competition outside of the U.S. In the U.S., SPINRAZA sales stabilized in the first half of 2022 compared to the same period last year, increasing two percent. TEGSEDI and WAYLIVRA revenue decreased due to the shift from product sales to distribution fees based on net sales generated by Sobi. The Company successfully completed the transition of its TEGSEDI and WAYLIVRA operations in the EU and North America to Sobi in the first and second quarters of 2021, respectively. As part of the transition, Ionis restructured its commercial operations in 2021 resulting in substantial cost savings. These decreases were partially offset by increasing licensing and royalty revenue. Operating Expenses Ionis is advancing a large late-stage pipeline and as a result, its non-GAAP operating expenses increased in the first half of 2022 compared to the same period in 2021. Higher R&D expenses were driven by the expanded number of Phase 3 studies the Company is conducting, which doubled from three to six studies in 2021. Lower SG&A expenses were largely due to the substantial savings Ionis achieved from integrating Akcea and restructuring its commercial operations in 2021. Ionis is redeploying these savings to advance its pipeline and go-to-market activities for eplontersen, donidalorsen and olezarsen. Net Loss Ionis' non-GAAP net loss in the first half of 2022 increased compared to the same period in 2021, primarily related to higher R&D expenses, partially offset by higher revenue and lower SG&A expenses, as discussed above. Balance Sheet As of June 30, 2022, Ionis had cash, cash equivalents and short-term investments of $2.0 billion, compared with $2.1 billion at December 31, 2021. Ionis' debt obligations and working capital did not change significantly from December 31, 2021 to June 30, 2022. Webcast Ionis will conduct a webcast today at 11:30 a.m. Eastern time to discuss this announcement and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. About Ionis Pharmaceuticals, Inc. For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing the standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming a leading, fully integrated biotechnology company. To learn more about Ionis visit or follow us on Twitter @ionispharma. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen), eplontersen, olezarsen, donidalorsen, ION363, pelacarsen, tofersen, Ionis' technologies and Ionis' other products in development. 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 those related to the impact COVID-19 could have on our business, and including 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. 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 December 31, 2021, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen. Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and costs related to the Akcea merger and restructured commercial operations and the related tax effects. Compensation expense related to equity awards are non-cash. Costs related to the Akcea merger and restructured commercial operations included: severance costs, retention costs and other costs related to commercial operations. Ionis has regularly reported non-GAAP measures for operating results as non-GAAP results. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations. Ionis' financial results for the first half of 2022 reflected the cost-sharing provisions related to its collaboration with AstraZeneca to develop and commercialize eplontersen for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is paying 55 percent of the costs associated with the ongoing global Phase 3 development program. Because Ionis is leading and conducting the Phase 3 development program, Ionis is recognizing the 55 percent of cost-share funding AstraZeneca is responsible for, net of Ionis' share of AstraZeneca's development expenses, as R&D revenue in the same period Ionis incurs the related development expenses. In the first half of 2022, Ionis earned $37 million in joint development revenue under this collaboration. Because AstraZeneca is responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., Ionis is recognizing cost-share funding it receives from AstraZeneca related to these activities as a reduction of its medical affairs (R&D expenses) and commercialization expenses (SG&A expenses). In the first half of 2022, Ionis recognized $0.8 million and $0.7 million of medical affairs expenses and commercialization expenses for eplontersen, respectively, net of cost-share funding from AstraZeneca. Ionis expects its medical affairs and commercialization expenses to increase as this collaboration progresses. SOURCE Ionis Pharmaceuticals, Inc.