Volanesorsen

关注并星标CPHI制药在线在全球人口老龄化推动下，心血管疾病一直是全球面临的严重疾病挑战。据公开资料，到2050年全球死于心血管疾病的人数将达3560万，对应市场规模达千亿美元。       以降脂明星靶点PCSK9为例，该赛道无论是传统药物还是新药销售额都亮眼。其中目前全球首个且唯一的siRNA药物Leqvio（英克司兰），由于利用siRNA技术实现了更显著的降脂疗效和更长的给药间隔（半年1次 ），极大地提升了患者依从性。基于此，Leqvio自2021年上市后，销售额连续三年高速增长，2024年达到7.54亿美元，同比增长114%。在心血管疾病高发的背景下，该赛道很多创新药物尚未达到商业化天花板，具有容纳更多药物的空间。因此，心血管疾病领域吸引了全球大小药企布局，为了实现差异化，药企们也在探索新型靶点研发。相比肿瘤、自免等其他热门疾病赛道，心血管疾病药物在市场端的优势十分明显。比如单药的使用人群广泛，立普妥的适应症就覆盖了从血脂异常到心血管事件全程管理。即便专利到期后，有多款仿制药上市，立普妥仍然占据重要的市场份额。再如，心血管疾病用药往往市场持续性长，降压药、降脂药都往往需要终身服用，全球处方量最大降压药之一的络活喜，在专利过期多年后，销售也依然强劲。拿下一款心血管疾病重磅药物，对于MNC而言，就是获得了专利独占期内业绩增长的压舱石。Lp(a)在降脂领域， 除了PCSK9外，Lp(a)（脂蛋白(a)）无疑是最热靶点。3月25日，恒瑞医药与默沙东就其Lp(a)口服小分子项目HRS-5346达成独家许可协议。根据条款，恒瑞将收取2亿美元的首付款，并有资格获得不超过17.7亿美元的特定开发、监管、商业化里程碑付款等。默沙东将获得HRS-5346在大中华区以外的全球范围内开发、生产和商业化的独家权利。这笔高额交易，将业界对Lp(a)的热情再次点燃。Lp(a)是一种由肝脏产生的脂蛋白，其水平升高被认为是冠状动脉疾病、心脏病发作和中风等心血管事件的独立危险因素，全球约20%人群Lp（a）水平偏高（50mg/dL）。但目前尚无针对Lp（a）升高的特效药。在研产品方面，目前进展最快的是诺华的Pelacarsen，这是一款反义寡核苷酸（ASO）药物，通过靶向并切割Apo（a） mRNA，来抑制Apo（a）蛋白的表达，阻断Lp（a）生成。Ⅱ期临床数据显示，Pelacarsen能将患者的Lp（a）水平降低约80%，80mg/月的给药剂量可使98%的患者Lp（a）水平降至50 mg/dL以下。目前Pelacarsen正在进行III期研究。与Pelacarsen不同，礼来的Lepodisiran是一种小干扰RNA（siRNA）疗法，旨在从基因翻译水平阻断Lp(a)的合成。在II期ALPACA研究中，在最高测试剂量（400mg）治疗后的第60天至第180天期间内，Lepodisiran使Lp(a)水平平均降低93.9%，达到了研究主要终点。接受Lepodisiran 16mg和96mg剂量的参与者在同一时间内，其Lp(a)水平分别降低了40.8%和75.2%。Lepodisiran在这项研究中显示的显著且持续的Lp(a)水平降低，表明siRNA疗法有望通过长期治疗而提供持久获益。同为siRNA疗法的Zerlasiran，由Silence Therapeutics开发，目前已经完成了IIa期临床试验，数据显示，300 mg剂量组患者在加收每16周一次的Zerlasiran治疗后，Lp（a）中位数降低89%，并维持48周。目前正进入IIb期临床试验阶段。国内方面，瑞博生物、舶望生物、赫吉亚生物、靖因药业的Lp（a）小核酸管线已取得临床进展。CETPCETP（胆固醇酯转移蛋白）是一种将胆固醇从HDL-C（好胆固醇）中转移到LDL-C（坏胆固醇）中的转运蛋白。它通过将胆固醇酯从HDL（高密度脂蛋白）转运至LDL（低密度脂蛋白）和VLDL（极低密度脂蛋白），并将甘油三酯从VLDL转运至LDL和HDL。因此，抑制CETP活性有助于升高HDL水平，并降低LDL和VLDL水平。当前在研CETP抑制剂包括Obicetrapib、CKD-508、MK-8262等。其中Obicetrapib由NewAmsterdam Pharma研发，是一种口服、选择性CETP抑制剂，在II期临床试验中，Obicetrapib单药或与Ezetimibe（依折麦布）联合均显著（所有指标P<0.05）降低患者的LDL-C（43.5%和63.4%）、非高密度脂蛋白胆固醇（non-HDL-C，37.5%和55.6%）、ApoB（24.2%和34.4%）、总低密度脂蛋白颗粒（LDL-P，54.8%和72.1%），并提高了高密度脂蛋白胆固醇水平（HDL-C，142%和136%）。目前，Obicetrapib已进入临床III期试验。ANGPTL3ANGPTL3（血管紧张素样蛋白3 ）是一种主要在肝脏中产生的蛋白，它的作用是抑制脂蛋白脂肪酶 ( LPL) 和内皮脂肪酶 (EL)。这两种酶负责分解富含甘油三酯的脂蛋白颗粒。当ANGPTL3水平升高时，它会抑制这些酶的活性，导致甘油三酯和胆固醇（包括LDL-C）在血液中堆积。反之，如果能降低ANGPTL3的水平，就能加速血脂的清除。针对ANGPTL3靶点，再生元公司的Evinacumab（依维苏单抗）于2021年获FDA批准上市，它是一种靶向ANGPTL3的全人源单克隆抗体，被批准用于治疗纯合子家族性高胆固醇血症（HoFH）患者。在研药物中，Arrowhead的Zodasiran是一种靶向ANGPTL3的RNA干扰(RNAi)药物，通过特异性降解ANGPTL3的mRNA，抑制肝脏中ANGPTL3的合成和分泌，从而降低血液中ANGPTL3的水平，改善脂质代谢。在一项II期ARCHES-2研究中，纳入204例混合型高脂血症成人患者，3:1随机分为Zodasiran组(50、100或200mg)或安慰剂组治疗，结果在第24周时，与安慰剂组相比，Zodasiran组的TG水平呈显著的剂量依赖性降低，Zodasiran50、100和200mg组的平均TG降幅分别达51%、57%和63%(P均<0.001)。与安慰剂组相比，Zodasiran组的ANGPTL3水平呈剂量依赖性降低，且与TG水平密切相关，Zodasiran50、100和200mg组的平均ANGPTL3降幅分别达54%、70%和74%。Zodasiran有望成为治疗混合型高脂血症的新选择，特别是对于那些对现有治疗反应不佳的患者。ApoC3ApoC3（载脂蛋白C3）主要在肝细胞中表达，可通过抑制脂蛋白脂肪酶（LPL）活性来增加血浆中甘油三酯水平；同时，通过干扰低密度脂蛋白受体对富含甘油三酯的脂蛋白（TRLs）及其残余物的清除来增加甘油三酯和胆固醇水平。因此，ApoC3可作为降血脂和心血管疾病的新兴靶点。针对ApoC3靶点，目前已获批上市药物有Akcea/Ionis的Waylivra（Volanesorsen）和Tryngolza（Olezarsen）。Volanesorsen是一种反义寡核苷酸（ASO）药物，于2019年5月获EMA批准上市，用于家族性乳糜微粒血症综合征（FCS）成年患者控制饮食之外的辅助疗法，FCS由LPL功能受损引起，患有FCS的患者可能出现严重的高甘油三酯血症和甘油三酯诱发的胰腺炎风险升高。Olezarsen也是由Ionis公司研发，同样是一款ASO疗法，旨在抑制机体产生ApoC3蛋白。FDA于2024年2月授予该疗法孤儿药资格和突破性疗法认定（BTD），并在12月批准其用于作为饮食控制的辅助治疗，以降低FCS成人患者的甘油三酯。在研产品方面，国内维亚臻生物的同类首创ApoC3 siRNA?疗法VSA001，于今年3月在中国FCS患者中的 III 期临床试验获得积极顶线数据，成功达到主要疗效终点和所有关键次要终点。已在国内报上市。瑞博生物的RBD5044，是全球第二个进入临床研究的靶向ApoC3 的siRNA管线，主要用于降血脂。其基于公司独有的RIBO-GalSTARTM肝靶向技术平台开发，通过siRNA介导ApoC3 基因沉默，能够高效、精准且持久地降低血浆中ApoC3 蛋白水平。与肿瘤、自免等热门疾病赛道相比，心血管疾病药物在市场端的优势十分明显，该领域盛产重磅炸弹药物。比如早期的立普妥，在2011年专利到期前，就累计为辉瑞创收超1400亿美元。即便专利到期后，立普妥仍然占据重要市场份额。还有小核酸药物乐可为，上市三年即步入重磅炸弹药物行列。因此，拿下一款心血管疾病重磅药物，意味着药企业绩基本有了保障。因此该赛道的竞争，激烈无比。以上是几个比较成熟的新兴靶点，有些尚无对应药物获批上市，谁能在这些新靶点中抢占先发优势，对业绩的增长将不可估量。参考来源：       1.Global burden of cardiovascular diseases: projections from 2025 to 2050. Eur J Prev Cardiol. doi: 10.1093/eurjpc/zwae281.?       2.https://doi.org/10.1056/NEJMoa2415818。       3.Kaasenbrood L, Boekholdt SM, van der Graaf Y, et? al. Distribution of estimated 10-year risk of recurrent vascular.       4.Durability and efficacy of solbinsiran, a GalNAc-conjugated siRNA targeting ANGPTL3, in adults with mixed dyslipidaemia (PROLONG-ANG3):?a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet.       5.https://ir.ionis.com/news-releases/news-release-details/ionis-announces-positive-topline-results-essence-study-olezarsen.END【企业推荐】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

– Strong revenue performance of $190 million – – Positive CHMP opinion for Sephience™ (sepiapterin) received in April 2025, NDA review remains on track for July 29, 2025 PDUFA date – – Global Sephience launch activities progressing well – – Strong cash position of over $2.0 billion as of March 31, 2025 – WARREN, N.J., May 6, 2025 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the first quarter ended March 31, 2025. "Following a year of outstanding execution across every part of the Company, we have built on this positive momentum with solid revenue performance in the first quarter, allowing us to narrow our full-year revenue guidance," said Matthew B. Klein, M.D., Chief Executive Officer. "Our strong cash balance supports all of our planned commercial and R&D activities and provides the ability to reach cashflow breakeven without raising additional capital. The positive CHMP opinion for Sephience kickstarts our anticipated global launch for what we see as a significant revenue opportunity." Key Corporate Updates: First quarter 2025 total net product and royalty revenue of $190 million. First quarter 2025 revenue for the DMD franchise of $134 million, including net product revenue for Translarna™ of $86 million and for Emflaza® of $48 million. Key Clinical and Regulatory Milestones: Sephience Positive CHMP opinion on Sephience MAA for adult and pediatric PKU patients received on April 25, 2025; the opinion includes a broad label inclusive of all ages and disease severities. PTC expects the EC to adopt the opinion in approximately two months NDA currently under review by the FDA, with a target regulatory action date of July 29, 2025 Japan regulatory submission under review and a decision is expected in Q4 2025 Vatiquinone NDA for pediatric and adult patients with Friedreich's ataxia accepted and granted Priority Review by the FDA, with a target regulatory action date of August 19, 2025 Translarna NDA currently under review by the FDA PTC518 Phase 2 PIVOT-HD study results announced on May 5, 2025: Met primary endpoint of dose-dependent blood HTT lowering at Week 12 Dose-dependent trends of clinical benefit in Stage 2 patients at Month 12 Signals of dose-dependent clinical benefit relative to matched natural history cohort and dose-dependent lowering of NfL in Stage 2 subjects at Month 24 Continued favorable safety and tolerability with no treatment-related NfL spikes Plans to complete additional analyses and discuss next development and regulatory steps, including potential for accelerated approval First Quarter 2025 Financial Highlights: Total net product and royalty revenue was $189.9 million for the first quarter of 2025, compared to $208.8 million for the first quarter of 2024. Total revenue includes net product revenue across the commercial portfolio of $153.4 million for the first quarter of 2025, compared to $177.6 million for the first quarter of 2024. Total revenue also includes royalty, collaboration and license, and manufacturing revenue of $1,022.7 million for the first quarter of 2025, compared to $32.5 million for the first quarter of 2024. The first quarter of 2025 collaboration and license revenue includes $986.2 million, related to the PTC518 license and collaboration agreement with Novartis, which closed in January 2025. Translarna net product revenues were $86.2 million for the first quarter of 2025, compared to $103.6 million for the first quarter of 2024. Emflaza net product revenues were $47.8 million for the first quarter of 2025, compared to $57.5 million for the first quarter of 2024. Roche reported Evrysdi® full year 2025 sales of approximately 420 CHF million, resulting in royalty revenue of $36.4 million to PTC for first quarter 2025, as compared to $31.2 million for first quarter 2024. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $109.0 million for the first quarter of 2025, compared to $116.1 million for the first quarter of 2024. Non-GAAP R&D expenses were $100.3 million for the first quarter of 2025, excluding $8.7 million in non-cash, stock-based compensation expense, compared to $107.2 million for the first quarter of 2024, excluding $9.0 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $81.0 million for the first quarter of 2025, compared to $73.3 million for the first quarter of 2024. Non-GAAP SG&A expenses were $71.6 million for the first quarter of 2025, excluding $9.4 million in non-cash, stock-based compensation expense, compared to $63.9 million for the first quarter of 2024, excluding $9.4 million in non-cash, stock-based compensation expense. Net income was $866.6 million for the first quarter of 2025, compared to net loss of $91.6 million for the first quarter of 2024. Cash, cash equivalents, and marketable securities were $2,027.2 million as of March 31, 2025, compared to $1,139.7 million as of December 31, 2024. Shares issued and outstanding as of March 31, 2025 were 79,225,276. PTC Updates Full-Year 2025 Financial Guidance: PTC now anticipates full-year 2025 revenue to be between $650 million and $800 million, which includes in-line products, potential new product launches, and royalty revenue from Evrysdi. PTC anticipates full-year 2025 GAAP R&D and SG&A expense to be between $805 and $835 million. PTC anticipates full-year 2025 non-GAAP R&D and SG&A expense to be between $730 and $760 million, excluding estimated non-cash, stock-based compensation expense of $75 million. Non-GAAP Financial Measures: In this press release, the financial results of PTC are provided in accordance with GAAP and using certain non-GAAP financial measures. In particular, the non-GAAP R&D and SG&A expense financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management's opinion, these non-GAAP financial measures are useful to investors and other users of PTC's financial statements by providing greater transparency into the historical and projected operating performance of PTC and the company's future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below. Acronyms: CHF: Confoederatio Helvetica Francs (Swiss francs) CHMP: Committee for Medicinal Products for Human Use DMD: Duchenne Muscular Dystrophy EC: European Commission FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles HD: Huntington's Disease HTT: Huntingtin protein MAA: Marketing Authorization Application NDA: New Drug Application NfL: Neurofilament light chain nmDMD: Nonsense mutation Duchenne muscular dystrophy PDUFA: Prescription Drug User Fee Act PKU: Phenylketonuria R&D: Research and Development SG&A: Selling, General, and Administrative Today's Conference Call and Webcast Reminder: To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in for the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investors section of the PTC website at . A replay of the call will be available approximately two hours after completion of the call and will be archived on the company's website for 30 days. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. The company's strategy is to leverage its strong scientific expertise and global commercial infrastructure to maximize value for its patients and other stakeholders. To learn more about PTC, please visit and follow on Facebook, X, and LinkedIn. For more information please contact: Investors: Ellen Cavaleri +1 (615) 618-8228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statements: This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including the information provided under the heading "PTC Updates Full Year 2025 Financial Guidance", including with respect to (i) 2025 total revenue guidance and (ii) 2025 GAAP and non-GAAP R&D and SG&A expense guidance, and statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance," "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; PTC's ability to maintain its marketing authorization of Translarna for the treatment of nmDMD in Brazil, Russia and other regions; the effect of the European Commission's adoption of the negative opinion from the Committee for Medicinal Products for Human Use (CHMP) on Translarna on other regulatory bodies; PTC's ability to use the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-label extension, and from its international drug registry study to support a marketing approval for Translarna for the treatment of nmDMD in the United States; whether investigators agree with PTC's interpretation of the results of clinical trials and the totality of clinical data from its trials in Translarna; expectations with respect to PTC's license and collaboration agreement with Novartis Pharmaceuticals Corporation including its right to receive development, regulatory and sales milestones, profit sharing and royalty payments from Novartis; expectations with respect to Upstaza/Kebilidi, including commercialization, manufacturing capabilities, and the potential achievement of sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to Sephience, including any regulatory submissions and potential approvals, commercialization, and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to vatiquinone, including any regulatory submissions and potential approvals, commercialization, and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to the commercialization of Evrysdi under PTC's SMA collaboration; expectations with respect to the commercialization of Tegsedi and Waylivra; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; PTC's ability to satisfy its obligations under the terms of its lease agreements; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Translarna, Emflaza, Upstaza, Kebilidi, Evrysdi, Tegsedi, Waylivra, Sephience or vatiquinone. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. 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