Inclisiran sodium

1月13日，第43届摩根大通医疗保健会议（JP Morgan Healthcare Conference）如期召开。昨天，医药魔方已经报道了强生、BMS、吉利德、辉瑞、再生元等制药巨头披露的最新公司发展动态和2025年战略。今天，医药魔方继续报道默沙东、拜耳、礼来、罗氏、诺华等跨国公司在过去一年的进展和未来规划。 ▌默沙东：将推出20个“重磅炸弹”，上调肿瘤业务收入预期 在过去几年，默沙东首席执行官Rob Davis经常要回答“如何面对Keytruda（帕博利珠单抗）专利悬崖逼近的威胁”这个问题。现在的他似乎对这个问题不那么焦虑了。 默沙东首席执行官Rob Davis 为了弱化对Keytruda的依赖性，默沙东在肿瘤领域进行了非常全面的布局，ADC、多抗、溶瘤病毒、癌症疫苗等应有尽有。Rob Davis在路演PPT中介绍道，2024年默沙东的III期在研产品数量相比于2021年几乎翻了两倍，并且在BD交易上前前后后投入了大约400亿美元。鉴于现有管线项目的潜力，默沙东再次将2030年的肿瘤业务收入预期提高，从200亿美元调整至250亿美元。 来源：默沙东JPM2025大会PPT 近两年，默沙东在ADC领域和炎症性肠病领域投入重金，手握多款first in class和best in class产品，其中ifinatamab deruxtecan（B7-H3 ADC）、zilovertamab vedotin（ROR1 ADC）和tulisokibart（TL1A单抗）皆已挺进III期阶段。 默沙东计划在后续几年推出20款潜在“重磅炸弹”药物，为其业绩增长提供新的动力。“我比以往任何时候都更有信心，我们有能力在未来十年及以后成为一家可持续发展、不断发展的公司。”Rob Davi对默沙东的未来充满了信心。 来源：默沙东JPM2025大会PPT ▌拜耳：多个领域新产品会爆发，期待新运营模式 拜耳在为Xarelto（利伐沙班）失去独家经营权做准备。拜耳处方药事业部总裁Stefan Oelric表示，拜耳正在推进前列腺癌、心血管疾病、女性健康、眼科等领域的新产品开发以安全渡过这个时期。 拜耳处方药事业部总裁Stefan Oelric 前列腺癌疗法Nubeqa（达罗他胺）、心血管产品Kerendia（非奈利酮）、女性更年期产品elinzanetant、Eylea/ Eylea HD（阿柏西普）是拜耳在路演PPT中重点提及的产品。 据拜耳新闻稿，Nubeqa现在是美国市场销售表现最好的AR抑制剂，其年销售额已经跨过“重磅炸弹”门槛，今年有望覆盖更广的前列腺癌治疗场景。Kerendia也有望在今年年底前新增心力衰竭适应症。拜耳相信，Kerendia未来将成为肾病领域和心力衰竭领域的重要疗法。Elinzanetant则是一种激素替代疗法，可以帮助存在更年期相关血管舒缩症状（VMS）的女性患者远离激素治疗带来的代谢紊乱烦恼。Stefan Oelric认为患者和医生都会喜欢这款，“我们认为elinzanetant是‘重磅炸弹’候选者，不然我们也不会推出这款产品。”至于阿柏西普，拜耳一直致力于优化其注射频率和注射方式，为眼科患者提供更便利的治疗。 来源：拜耳JPM2025大会PPT 去年1月，拜耳推出了新的公司运营模式，希望通过精简组织架构来加快决策。为此，拜耳已在全球进行了多轮裁员。Stefan Oelrich表示，“我们的新运营模式显然正在成为推动业绩增长和提高运营效率的关键推动因素。” 来源：拜耳JPM2025大会PPT ▌礼来：GLP-1药物销售不及预期 礼来在今年的JPM会议上分享了其2024年销售业绩基本情况，预计2024年全年收入约为 450亿美元，虽然这一数字相比2023年增长了32%，但相比去年10月份第三季度财报中提出的收入预期下限低了4亿美元。肠促胰岛素药物市场增长似乎未及该公司或行业分析师预期。 来源：礼来JPM2025大会PPT “今年GLP-1市场的反应与往年不同，往年通常在12月时需求会增加。”礼来首席执行官David Ricks表示，今年GLP-1市场没有出现这种情况，推测与联邦医疗保险Medicare Part D和保险条款变化相关。David Ricks对销售额不及预期进一步解释道，减重是新兴市场，在销售额预测方面仍有很多需要学习的地方。 礼来首席执行官David Ricks 礼来指出，GLP-1市场有许多增长途径。上个月礼来的Zepbound（替尔泊肽）获批用于治疗睡眠呼吸暂停，“每个新增新适应症都会扩大药物的市场空间”。此外，对于礼来而言，美国以外的市场目前尚未充分挖掘，也是潜在的业务增长来源。 展望未来，礼来预计2025年营收将增长，部分得益于一些新药，如癌症药物Jaypirca（匹妥布替尼）、特应性皮炎治疗药物Ebglyss（来金珠单抗）、溃疡性结肠炎药物Omvoh（米吉珠单抗）和阿尔茨海默病治疗药物Kisunla（多奈单抗）。礼来预计2025年全年销售额在580-610亿美元之间，按中点计算增长32%，与2024年的增幅持平。Ricks还强调了礼来在糖尿病和减重产品之外的实力，“如果不谈肠促胰岛素和GLP-1类药物，礼来可能是其他领域业务增长最快的大公司。” ▌罗氏：每年有100亿美元可用于并购，将继续寻找中国资产 罗氏公司制药部门首席执行官Teresa Graham在会议上表示，罗氏每年约有100亿美元的并购资金可供调配，但“不会随意花钱”。Graham表示，如果找到对现有产品组合有补充作用的资产，或者在公司关注领域之外的重要疾病治疗领域带来变革的资产，罗氏已准备好动用这笔资金。 罗氏公司制药部门首席执行官Teresa Graham 去年秋天，罗氏公布了最新药物开发战略，重点关注神经学、肿瘤学/血液学、免疫学、眼科学和心血管/肾脏/代谢（CVRM）五大治疗领域。罗氏近期在这些重点领域达成的交易包括与信达生物达成的DLL3 ADC合作、15亿美元收购CAR-T合作伙伴Poseida Therapeutics，以及以8.5亿美元预付款从中国锐格医药获得一系列CDK抑制剂的授权许可等。Graham指出，罗氏将继续寻找优质中国资产。 来源：罗氏JPM2025大会PPT 此外，罗氏最近对其内部研发管线进行了仔细评估，并终止了约30%的研发项目。“由于我们从产品组合中剔除了许多项目，现在就有了更多资源来投资新的内部和外部项目。”Graham称，到2026年，罗氏的后期研发项目将与现在“有很大不同”，在未来18个月内，大约有18个项目进入或完成后期临床研究。 ▌诺华：8款产品销售额将达到30-80亿美元 诺华首席执行官Vas Narasimhan指出，在经历了剥离爱尔康和山德士等一系列调整之后，诺华已经转型为一家纯粹的创新药品公司，与此同时，公司的业绩近年来也保持强势增长，带来了强劲的现金流及不错的投资回报率。 诺华首席执行官Vas Narasimhan 诺华将乳腺癌药物Kisqali（瑞波西利）视为最重要的增长驱动力，Vas Narasimhan在演讲中表示：“Kisqali将成为诺华有史以来最畅销的药物之一。该疗法的峰值销售额可能超过80亿美元。就目前情况而言，Kisqali在美国早期乳腺癌市场拥有52%的市场份额、在转移性乳腺癌市场拥有50%的市场份额。 除Kisqali外，诺华旗下还有7款产品的年销售有望达到30-80亿美元，包括Entresto、Cosentyx、Kesimpta、Pluvicto、Leqvio、Scemblix、Fabhalta。 来源：诺华JPM2025大会PPT 诺华将依然执行此前的重点战略，聚焦化学、生物治疗学、RNA疗法、放射配体疗法、基因与细胞治疗技术。 来源：诺华JPM2025大会PPT ▌GSK：今年预计将有5款产品迎来获批 GSK首席执行官Emma Walmsley在会议上表示，预计2025年将有5款产品迎来获批消息，包括用于多发性骨髓瘤的Blenrep、治疗嗜酸性粒细胞相关疾病的depemokimab、针对慢性阻塞性肺疾病（COPD）的Nucala、新型口服抗生素gepotidacin以及5-in-1疫苗MenABCWY。其中最重要的是BCMA抗体偶联药物Blenrep，该疗法此前在一项多发性骨髓瘤试验中，总生存期超过强生Darzalex，引起业界轰动。这些产品基于GSK现有专长研发，有望带来显著市场价值。 对于美国反疫苗运动趋势，Walmsley回应，“在医疗预算方面，没有什么能比让人们远离医院回报更高。我们完全欢迎关于疫苗功效和质量的任何辩论或质疑，我们需要以透明和信任的态度参与这些对话。” GSK首席执行官Emma Walmsley 美国市场对于GSK来说至关重要。Walmsley指出，“美国市场业务占比超过 50%，我们不久前刚在宾夕法尼亚州投资8亿美元用于药品和疫苗生产，”GSK依然会全力投入美国市场。 医药魔方将持续关注JPM2025动态，敬请期待！ 推荐阅读 JPM2025 Day1 | 强生、BMS、吉利德、辉瑞、再生元……制药巨头纷纷披露新战略 Copyright © 2025 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。

Jan 12, 2025 – Full Year 2024 Preliminary Net Product Revenues of $1,646 Million for ONPATTRO®, AMVUTTRA®, GIVLAARI®, and OXLUMO®, Representing 33% Annual Growth – – 2025 Combined Net Product Revenue Guidance** of $2,050 Million to $2,250 Million Positions Company to Achieve Alnylam P5x25 Goal of Non-GAAP Profitability – – Robust Clinical Pipeline with Multi-Billion-Dollar Opportunities for Sustainable Growth – CAMBRIDGE, Mass. --(BUSINESS WIRE)--Jan. 12, 2025-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced its preliminary* fourth quarter and full year 2024 global net product revenues for ONPATTRO, AMVUTTRA, GIVLAARI, and OXLUMO. In addition, the Company provided 2025 net product revenue, non-GAAP operating income profitability, and pipeline goals guidance. “Alnylam’s commercial and clinical achievements in 2024 position us very well for another transformative year in 2025, as we continue to evolve into a global, top-tier biotech company,” said Yvonne Greenstreet , MBChB, Chief Executive Officer of Alnylam . “We generated net product revenues for the year of over $1.6 billion , representing growth of 33% compared to 2023, at the high end of our revised guidance range, and demonstrating the strength of our underlying hATTR-PN and Rare businesses. We expect 2025 will represent an important inflection point for our TTR franchise, with the potential launch of vutrisiran in ATTR-CM delivering significant topline growth as reflected in our net product sales guidance announced today. If we are successful in meeting this product revenue guidance, we anticipate achieving non-GAAP profitability in 2025.” Dr. Greenstreet continued, “We’re also looking forward to a year of major advancements in our pipeline and RNAi platform, with key goals outlined today. This remarkable pace of progress positions us well to finish the year achieving key Alnylam P5x25 goals and to continue delivering sustainable innovation to patients through our global commercial infrastructure, broad pipeline, and organic platform.” Preliminary Fourth Quarter and Full Year 2024 Commercial and Financial Performance* Total TTR: ONPATTRO® (patisiran) & AMVUTTRA® (vutrisiran) Preliminary* global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter were approximately $56 million and $287 million , respectively, representing together 35% total TTR annual growth compared to Q4 2023, and for the full year 2024 were approximately $253 million and $970 million , respectively, representing together 34% total TTR annual growth compared to full year 2023. Total Rare: GIVLAARI® (givosiran) & OXLUMO® (lumasiran) Preliminary* global net product revenues for GIVLAARI and OXLUMO for the fourth quarter were approximately $65 million and $44 million , respectively, representing together 18% total Rare annual growth compared to Q4 2023, and for the full year 2024 were approximately $256 million and $167 million , respectively, representing together 29% total Rare annual growth compared to full year 2023. 2025 Combined Net Product Revenue & Non-GAAP Operating Income Guidance Alnylam announced today full year 2025 combined net product revenue guidance for ONPATTRO, AMVUTTRA (PN & CM**), GIVLAARI and OXLUMO of $2,050 million to $2,250 million , representing combined full year growth compared to 2024 of 31% at the mid-point of the guidance range. On a franchise level, the guidance is broken down as follows: Total TTR (ONPATTRO, AMVUTTRA (PN & CM**)): $1,600 million to $1,725 million , representing full year growth compared to 2024 of 36% at the mid-point of the guidance range. Total Rare (GIVLAARI, OXLUMO): $450 million to $525 million , representing full year growth compared to 2024 of 15% at the mid-point of the guidance range. In addition, the Company anticipates delivering non-GAAP operating income profitability in 2025. The Company plans to provide additional guidance for collaboration and royalty revenue and operating expenses at the time fourth quarter and full year 2024 earnings are released. 2025 Product and Pipeline Goals Vutrisiran – an RNAi therapeutic marketed in various countries globally as a treatment of adults with hATTR amyloidosis with polyneuropathy, and in development for the treatment of adults with ATTR amyloidosis with cardiomyopathy. Alnylam expects to: Achieve U.S. Food and Drug Administration (FDA) approval of the supplemental New Drug Application for the treatment of adults with ATTR amyloidosis with cardiomyopathy by the PDUFA target action date of March 23, 2025 . Secure additional global approvals and reimbursement in Japan and the EU for the treatment of adults with ATTR amyloidosis with cardiomyopathy in the second half of 2025. Nucresiran (ALN-TTRsc04) – an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam expects to: Initiate a Phase 3 study in patients with ATTR amyloidosis with cardiomyopathy in the first half of 2025. Zilebesiran – an investigational RNAi therapeutic in development for the treatment of hypertension, in collaboration with Roche. Alnylam expects to: Report results from the KARDIA-3 Phase 2 study in the second half of 2025. Initiate a Phase 3 cardiovascular outcomes trial in the second half of 2025. Mivelsiran – an investigational RNAi therapeutic in development for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). Alnylam expects to: Report interim results from Part B of the Phase 1 study in Alzheimer’s disease in the second half of 2025. Initiate a Phase 2 study in Alzheimer’s disease in the second half of 2025. ALN-6400 – an investigational RNAi therapeutic in development for the treatment of bleeding disorders. Alnylam expects to: Initiate a Phase 2 study in a bleeding disorder in the second half of 2025. In addition, the Company plans to file Investigational New Drug (IND) applications for four new Alnylam -led programs by the end of 2025. Partner-Led Program Highlights Alnylam partnered programs continue to progress, including: Fitusiran – an investigational RNAi therapeutic partnered with Sanofi in development for the treatment of hemophilia A and B, with or without inhibitors. Sanofi expects to secure FDA approval by the PDUFA target action date of March 28, 2025 . Elebsiran – an investigational RNAi therapeutic partnered with Vir Biotechnology in development for the treatment of chronic hepatitis B and chronic hepatitis delta. In 2025, Vir expects to initiate a Phase 3 chronic hepatitis delta registrational study and to report functional cure results from a Phase 2 chronic hepatitis B study. Alnylam management will discuss its preliminary 2024 net product revenues, as well as 2025 goals and guidance during a webcast presentation at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California tomorrow, Monday, January 13, 2025 at 9:45 am PT ( 12:45 pm ET ). About RNAi Therapeutics RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram. Alnylam Forward Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding Alnylam’s evolution into a leading, global, top-tier biotech company; Alnylam’s expectations regarding the potential approval and launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy in the U.S. in early 2025 and in other territories in the second half of 2025; the potential that the launch of AMVUTTRA for ATTR-CM will deliver significant topline growth for Alnylam ; the potential for 2025 to be a transformative year for Alnylam and that 2025 will represent an important inflection point for Alnylam’s TTR franchise; Alnylam’s ability to deliver non-GAAP operating income profitability in 2025; the potential for 2025 to be a year of major advancements in Alnylam’s pipeline and RNAi platform; Alnylam’s potential achievement of the goals in its “Alnylam P5x25” strategy; Alnylam’s ability to continue to deliver sustainable innovation to patients through its global commercial infrastructure, broad pipeline and organic platform; the potential for Alnylam to advance its research and development programs, including its goals and expectations regarding the clinical development of vutrisiran, nucresiran, zilebesiran, mivelsiran, ALN-6400, and its earlier stage programs, and its partners’ expectations for Alnylam’s partnered programs; and Alnylam’s projected commercial and financial performance, including the expected range of net product revenues and non-GAAP operating income for 2025, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “Alnylam P5x25” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran, nucresiran, zilebesiran, mivelsiran and ALN-6400; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the approved indications for AMVUTTRA in the future; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products, including Roche, Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the risk of future government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC . In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. Vutrisiran has not been approved by any regulatory agency for the treatment of ATTR amyloidosis with cardiomyopathy. No conclusions can or should be drawn regarding its safety or effectiveness in treating cardiomyopathy in this population. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval. Use of Non-GAAP Financial Measures This press release contains a non-GAAP financial measure of non-GAAP operating income. This measure is not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies. Stock-based compensation expense is included in GAAP operating income but excluded for purposes of determining non-GAAP operating income. The Company has excluded the impact of stock-based compensation expense as it may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. * The preliminary selected financial results are unaudited, subject to adjustment, and provided as an approximation in advance of the Company’s announcement of complete financial results in February 2025 . ** Guidance assumes FDA approval of the sNDA for vutrisiran for the treatment of adults with ATTR amyloidosis with cardiomyopathy by the March 23, 2025 PDUFA target action date. View source version on businesswire.com: https://www.businesswire.com/news/home/20250112711585/en/ Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom (Investors and Media) 617-682-4340 Josh Brodsky (Investors) 617-551-8276 Source: Alnylam Pharmaceuticals, Inc.