Deflazacort

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。 四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。 杜氏肌营养不良症（Duchenne Muscular Dystrophy，DMD）是一种致命的、进行性的肌肉萎缩性疾病，由编码抗肌萎缩蛋白（dystrophin）的基因发生变异导致。全球范围内，大约每3500-5000名男性新生儿中就有1名DMD患儿，每年有2万名儿童确诊DMD。这些患者的肌无力症状在2-3岁时就会显现，并随着年龄逐渐加重。在缺乏有效治疗的情况下，疾病进展通常导致患者在12岁左右便需借助轮椅行动，多数人的生命会因心肺并发症在青少年时期或二十岁出头时就走到尽头。 过去30多年来，随着皮质类固醇的使用、无创呼吸支持以及DMD相关并发症的主动监测和管理，该病患者的运动能力、身体功能、生活质量和预期寿命均已获得显著改善。近十年来，多种针对DMD根本病因——抗肌萎缩蛋白缺失的创新疗法相继涌现，为延缓、甚至逆转疾病进展带来了前所未有的希望。在这场迎战DMD的攻坚征程中，药明康德深感荣幸能够与全球合作伙伴并肩前行，持续赋能DMD领域创新疗法的开发与落地，将前沿科学突破转化为患者的生命希望。 图片来源：123RF 跨越百年揪出肌肉无力的病因 杜氏肌营养不良症这个疾病名称，来自一位19世纪的法国医生——纪尧姆-本杰明-阿曼德·杜兴（Guillaume-Benjamin-Amand Duchenne）。杜兴医生一生痴迷于探索神经与肌肉疾病，常年穿梭于巴黎各大医院的病房之间，执着地寻找并记录那些罕见的病例。 凭借对每一位患者的细致观察和系统记录，杜兴医生精准描述了许多当时未知的神经肌肉病症。1861年，他在著作中记录了一种特殊的进行性肌无力疾病，并将其命名为“假性肥大型肌营养不良”——患者最显著的特征是小腿的腓肠肌看似粗壮发达，实则肌力显著减弱。1868年，他通过对13例同类病例的系统总结，提供了当时对该病最全面的临床描述，为其作为独立疾病的认知奠定了基础。因此，尽管后世发现杜兴医生可能并非最早注意到该病的人，医学界仍然决定用他的名字来命名这种疾病，以此表彰和纪念他的重要贡献。 此后，科学家们曾提出各种假说试图解释这类患者的肌肉为何会逐渐坏死，但均未获证实。直至一个多世纪后，基因研究的突破才最终揭示：这种疾病的根源，在于编码抗肌萎缩蛋白的基因发生了变异。 “治标”措施显著延长患者预期寿命 在健康的肌肉组织中，抗肌萎缩蛋白就像一个减震器，能在肌肉细胞收缩和舒张时起稳定作用。而患有DMD的患者产生的抗肌萎缩蛋白很少或者根本就不生产，这使得肌肉在收缩过程中不断受损、发炎，最终被脂肪和瘢痕组织替代，丧失功能。 ▲DMD患者和健康人的肌肉横断面染色对比图（图片来源：参考资料[1]） DMD的病情进展通常始于下肢肌肉，尤其是腓肠肌、胫骨前肌和趾长伸肌等肌群。随着肌无力向全身蔓延，该病后期还会累及呼吸肌和心肌，导致呼吸功能衰竭和心力衰竭，这是DMD患者的两大主要致死原因。在很长一段时间内，DMD由于缺乏有效的治疗手段，患者的中位预期寿命不足26岁。 然而，过去三十多年来，DMD综合治疗与系统性护理的发展显著改善了患者的预后。尤其是在心肺功能支持方面，通过机械辅助咳嗽和无创通气技术优化呼吸管理，以及早在10岁左右起推荐患者使用血管紧张素转换酶抑制剂（ACEI）进行心功能保护，有效延缓了患者心肺并发症的进展。据2013年的一项研究显示，1970年后出生的DMD患者的中位生存期已延长至超过40岁。 除了这两方面，皮质类固醇的使用在DMD临床治疗中也占据着重要地位。国际指南强烈建议在患儿运动功能进入平台期或开始下降时（通常为4-5岁，不早于2岁）启动激素治疗，并建议长期使用。这类药物已被证实可有效延缓肌力衰退、维持行走能力、保护心肺功能并减少脊柱侧弯的发生。目前，经FDA批准用来治疗DMD的皮质类固醇药物包括Emflaza（deflazacort）和Agamree（vamorolone）。 除了类固醇这类基础抗炎药物外，2024年3月，美国FDA批准了一款新型机制药物——Duvyzat（givinostat）。作为首个获批可用于治疗携带任何DMD基因变异患者的非类固醇疗法，Duvyzat旨在通过抑制DMD患者中异常升高的组蛋白去乙酰化酶（HDAC）活性，缓解肌肉组织的损害，保护肌肉超细纤维的功能，从而为此类患者提供一种全新的治疗策略，也与类固醇激素形成了重要的协同与补充。 然而，上述方法对于DMD患者来说还是“治标不治本”。尽管许多患者的生存时间得到了延长，其肌肉功能的持续下降依然会严重影响生活质量。患者家庭和医疗界都迫切期待能够找到“根治”DMD的新疗法，以期真正改善患者的运动功能与生活品质。 针对DMD疾病根源的新治疗模式 对于如何“根治”DMD的问题，科学家们的思路是，既然DMD的产生源于抗肌萎缩蛋白的缺失，那么提高抗肌萎缩蛋白的表达，就有望恢复肌肉细胞的功能，减少肌肉细胞的损伤。实现这一目标的关键在于修正发生变异的DMD基因，或直接向细胞内递送一个完整的健康基因。 1990年发表的一例特殊病例报告给科学家们提供了一个关键启示。在该案例中，一名男子的抗肌萎缩蛋白基因缺失了将近一半，却没有出现肌肉无力的症状，并且还活到了61岁。 这个案例表明：即使基因不完整，机体仍有可能产生具备足够功能的截短蛋白，以维持正常的生理活动。这为开发DMD治疗策略开辟了全新思路：如果完全修复DMD基因存在巨大的技术挑战，不如“弃车保帅”。比如，科学家们可以跳过那些出问题的、非关键的基因片段，合成仍有功能的“简化版”蛋白质。 针对DMD的外显子跳跃疗法应运而生。这种新型疗法的作用机制是，通过让寡核苷酸疗法与编码抗肌萎缩蛋白的mRNA前体结合，改变mRNA前体的剪接过程，跳过携带基因突变的DMD外显子，从而生成具有大部分抗肌萎缩蛋白功能的截短蛋白。 2016年，由Sarepta Therapeutics公司研发的首个外显子跳跃疗法Exondys 51（eteplirsen）获FDA批准上市，适用于适合外显子51跳跃治疗的DMD患者。临床试验数据显示，接受180周治疗后，患者肌肉中的抗肌萎缩蛋白水平达到了对照组的11.6倍。 此后，多款类似药物相继问世，包括Sarepta Therapeutics公司的Vyondys 53（golodirsen），Amondys 45（casimersen），以及Nippon Shinyaku公司的Viltepso（viltolarsen），分别针对不同的外显子跳跃类型，惠及更广泛的DMD患者群体。 ▲以Viltepso（又名NS-065）为例展示的寡核苷酸疗法作用机制（图片来源：Nippon Shinyaku公司官网） 值得一提的是，所有4款获批的寡核苷酸疗法均采用了磷二酰胺吗啉寡聚物（PMO）技术。PMO是一类基于RNA天然框架设计的合成分子，其碱基与吗啉环相连，并通过磷酰二胺键进行连接，而非天然RNA中的核糖环与磷酸二酯键。这一特殊结构使PMO能够高效、稳定地与靶标mRNA前体结合，同时在体内表现出优异的抗降解能力，为外显子跳跃策略提供了坚实的技术基础。 首款DMD基因疗法诞生 对于DMD这类单基因遗传病，理论上的治愈方法之一是通过基因疗法向患者体内递送一个功能正常的基因拷贝，从而持久地表达所需蛋白。然而，DMD基因疗法的开发面临两大严峻挑战：第一，常用作递送载体的病毒天然倾向感染肝脏和肺，难以高效靶向肌肉组织；第二，DMD基因尺寸巨大，远超常用病毒载体的装载容量，导致全长基因无法被递送。 转机出现在1996年。当时，北卡罗来纳大学的裘德·萨穆尔斯基（Jude Samulski）博士团队成功设计出了能够感染肌肉细胞的腺相关病毒（AAV）。随后，一些科学家也相继开发出了大小适合病毒载体的精简版抗肌萎缩蛋白——微抗肌萎缩蛋白（micro-dystrophin）。2006年，6名肌肉萎缩症患者接受了一种局部注射的DMD基因疗法，证实了萨穆尔斯基博士的AAV病毒能够安全地将微抗肌萎缩蛋白基因递送到人类的肌肉细胞中。 这次关键性的成功，极大地激励了研究团队向终极目标发起挑战：开发出一种能够实现全身给药的基因疗法。历过十年的不懈探索和反复优化，一款代号为SRP-9001的新型基因疗法终于诞生。该疗法在临床试验中取得了令人振奋的效果。例如，一名4岁的DMD患儿在接受治疗后仅3天，运动能力就有了明显提升——从之前上楼困难，变为可以双脚交替上下楼梯；治疗11天后，他甚至能够尝试骑自行车。这些积极的早期信号，为疗法的后续推进注入了强大信心。 图片来源：123RF 2023年6月，这款由Sarepta Therapeutics公司与罗氏（Roche）联合开发的基因疗法Elevidys（delandistrogene moxeparvovec）获得了美国FDA的加速批准，用于治疗4-5岁、携带特定DMD基因突变的患儿。Elevidys也是首个获FDA批准上市的用于治疗DMD的一次性基因疗法，它的获批标志着DMD治疗领域的又一重大进展，从此，医护人员可以为DMD患者提供针对疾病根本成因的治疗方法，而不仅仅是控制症状。 2024年6月，美国FDA批准Elevidys扩展适应症，适用于所有4岁及以上、经确诊携带DMD基因突变的患者。这是该疗法自首次获批后的一个重要进展，意味着更多DMD患者有机会接受这种一次性治疗。 CRDMO平台护航新药研发行稳致远 回望DMD领域的发展历程，近十年来美国FDA批准的8款疗法中，有5款属于针对疾病根本病因的寡核苷酸疗法与基因疗法，标志着该方向已成为DMD新药研发的重要领域。公开资料显示，目前全球范围内有超过40个DMD在研项目，其中约半数聚焦于基因疗法和寡核苷酸疗法，展现出该领域持续的创新活力与发展潜力。 其中，寡核苷酸疗法凭借其高度靶向性、灵活可编程和相对较短的开发周期，吸引了产业界的广泛关注。在这一进程中，偶联技术的进步成为推动疗法突破的关键驱动力。然而，诸如PMO等类型的寡核苷酸分子在合成与生产方面极为复杂，也为企业带来了显著的技术与产业化挑战。 作为全球赋能寡核苷酸药物研发的一体化、端到端的CRDMO平台，药明康德依托在化学业务领域二十年的深厚积累，为此类创新疗法的开发与产业化提供了坚实支撑。药明康德化学业务平台的WuXi TIDES团队目前具备PMO单体、PMO、多肽、多肽-PMO（PPMO）偶联及制剂开发的综合能力。公开信息显示，WuXi TIDES在多肽和寡核苷酸等新分子的开发和生产方面持续精进平台能力，通过不断优化工艺、内部整合流程提供一体化服务，在3年内将PMO类药物活性成分（API）成本降低60%。 在寡核苷酸的偶联方面，WuXi TIDES全面的平台能力可支持寡核苷酸与多肽、脂质、小分子、毒素/药物等组件的偶联，为复杂的寡核苷酸偶联药物提供一体化解决方案。以2024年药明康德投资者开放日上展示的赋能案例为例：针对将多肽与PMO偶联，生产技术极为复杂的PPMO疗法，WuXi TIDES团队寡核苷酸、多肽、制剂、分析等6个团队平行推进、无缝衔接，仅用11个月将其推进至IND申报阶段。这也得益于药明康德在CMC一体化解决方案方面的专长。 成立二十五年来，药明康德始终致力于赋能全球合作伙伴加速创新疗法开发，助力更多突破性疗法早日惠及患者。药明康德也期待与业界同仁继续携手，以CRDMO平台之力为新药研发“护航”，共同推动人类健康事业行稳致远。 参考资料： [1] Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021 Feb 18;7(1):13. doi: 10.1038/s41572-021-00248-3. [2] Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health. 2015 Aug;51(8):759-64. doi: 10.1111/jpc.12868. [3] Guillaume-Benjamin-Amand Duchenne Biography (1806-1875). Retrieved August 28, 2025, from http://www.faqs.org/health/bios/99/Guillaume-Benjamin-Amand-Duchenne.html [4] Maranhão-Filho P, Vincent M. Guillaume-Benjamin Duchenne: a miserable life dedicated to science. Arq Neuropsiquiatr. 2019 Jul 15;77(6):442-444. doi: 10.1590/0004-282X20190044. 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

– European and FDA approval of Sephience™ (sepiapterin) with broad labeling for PKU – – Global launch underway in Europe and U.S. – – Total Q2 Revenue of $179M – WARREN, N.J., Aug. 7, 2025 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the second quarter ended June 30, 2025. "We had another strong quarter highlighted by the first approvals of Sephience for the treatment of children and adults with PKU," said Matthew B. Klein, M.D., Chief Executive Officer. "We have initiated the global launch and expect Sephience to be the foundational product for PTC's future growth and path to profitability." Key Corporate Updates: Second quarter 2025 total net product, collaboration and royalty revenue of $179 million Second quarter 2025 revenue for the DMD franchise of $96 million, including net product revenue for Translarna™ of $59 million and for Emflaza® of $36 million Initiated global launch of Sephience™ in the U.S. and Germany as well as in other countries through early access and named patient programs Entered into agreement to purchase the Sephience annual percentage-based global net sales obligation owed to former Censa shareholders in exchange for an upfront payment of $225 million and future sales milestone payments Key Clinical and Regulatory Milestones: Sephience™ (sepiapterin) Marketing authorization granted by the EC on June 19, 2025 with broad label inclusive of all disease subtypes and all ages FDA approval on July 28, 2025 with broad label inclusive of all disease subtypes and all ages, from 1 month of age upwards Japan NDA review is ongoing with decision expected in Q4 2025 NDA reviews for vatiquinone (Friedreich's ataxia) and Translarna (nonsense mutation DMD) are ongoing, with regulatory action date of August 19, 2025 for vatiquinone In May 2025, reported positive Phase 2 PIVOT-HD study results for votoplam (PTC518) in Huntington's Disease patients. PTC continues to collaborate with Novartis on next steps and aims to meet with FDA in Q4 2025 to discuss Phase 3 clinical trial design and potential accelerated approval pathway. Second Quarter 2025 Financial Highlights: Total revenues were $178.9 million for the second quarter of 2025, compared to $186.7 million for the second quarter of 2024. Total revenue includes net product revenue across the commercial portfolio of $118.3 million for the second quarter of 2025, compared to $133.2 million for the second quarter of 2024. Total revenue also includes royalty, collaboration and license, and manufacturing revenue of $60.5 million in the second quarter of 2025, compared to $53.5 million for the second quarter of 2024. Translarna net product revenues were $59.5 million for the second quarter of 2025, compared to $70.4 million for the second quarter of 2024. Emflaza net product revenues were $36.4 million for the second quarter of 2025, compared to $47.3 million for the second quarter of 2024. Roche reported Evrysdi® first half 2025 sales of approximately 869 CHF million, resulting in royalty revenue of $57.6 million to PTC for second quarter 2025, as compared to $53.2 million for second quarter 2024. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $113.0 million for the second quarter of 2025, compared to $132.2 million for the second quarter of 2024. Non-GAAP R&D expenses were $104.0 million for the second quarter of 2025, excluding $9.0 million in non-cash, stock-based compensation expense, compared to $122.7 million for the second quarter of 2024, excluding $9.4 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $85.3 million for the second quarter of 2025, compared to $69.5 million for the second quarter of 2024. Non-GAAP SG&A expenses were $75.7 million for the second quarter of 2025, excluding $9.5 million in non-cash, stock-based compensation expense, compared to $59.7 million for the second quarter of 2024, excluding $9.8 million in non-cash, stock-based compensation expense. Net loss was $64.8 million for the second quarter of 2025, compared to net loss of $99.2 million for the second quarter of 2024. Cash, cash equivalents, and marketable securities were $1,989.2 million as of June 30, 2025, compared to $1,139.7 million as of December 31, 2024. Shares issued and outstanding as of June 30, 2025, were 79,378,145. PTC Full-Year 2025 Financial Guidance: PTC anticipates full-year 2025 revenue to be between $650 million and $800 million, which includes in-line products, new and potential 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) DMD: Duchenne Muscular Dystrophy EC: European Commission FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles NDA: New Drug Application nmDMD: Nonsense mutation Duchenne muscular dystrophy 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 dedicated to the discovery, development and commercialization of clinically differentiated medicines for children and adults living with rare disorders. PTC is advancing a robust and diversified pipeline of transformative medicines as part of its mission to provide access to best-in-class treatments for patients with unmet medical needs. The company's strategy is to leverage its scientific expertise and global commercial infrastructure to optimize value for 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 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," "aim," 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 Quarterly Report on Form 10-Q and 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 Sephience, Translarna, Emflaza, Upstaza, Kebilidi, Evrysdi, Tegsedi, Waylivra 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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