INTERFERON BETA-1A(Merck Serono SA)

Company delivered on financial guidance for 2025 Net sales around stable at € 21.1 billion; organic growth of +3.1%; foreign exchange effects of –3.7% EBITDA pre grew to € 6.1 billion; organic growth of +5.6%; foreign exchange effects of –5.0% Executive Board and Supervisory Board propose stable dividend of € 2.20 per share Outlook 2026: Net sales of € 20.0 – 21.1 billion and EBITDA pre of € 5.5 – 6.0 billion amid considerable foreign exchange headwinds Merck KGaA, Darmstadt, Germany, a leading science and technology company, delivered on its guidance for 2025 and achieved organic growth despite significant headwinds. Process Solutions in the Life Science business sector, the Cardiovascular, Metabolism & Endocrinology (CM&E) franchise within Healthcare and the Semiconductor Materials business within Electronics were the main contributors. “We once again demonstrated our resilience in 2025 in the face of significant geopolitical challenges and strong currency headwinds. Our consistent record of disciplined financial performance and sharp strategic focus over the last five years has paid off and made us larger, more profitable, more efficient, more flexible, and less leveraged. I’m very proud of where we stand today,” said Belén Garijo, Chair of the Executive Board and CEO of Merck KGaA, Darmstadt, Germany. “As a diversified global business with a robust portfolio and core growth drivers in Process Solutions, Rare Diseases and Semiconductor Solutions, we are now well positioned for the decade ahead as our company’s next chapter begins.” Financial performance in 2025 In 2025, net sales of the Group grew organically by 3.1% compared with the previous year. Reported net sales declined by 0.3% to € 21.1 billion, mainly driven by a negative impact of –3.7% from foreign exchange effects concerning the U.S. dollar and various Asian currencies. Portfolio effects, especially the acquisition of SpringWorks and the divestment of the Surface Solutions business unit, made a net positive contribution of 0.4%. In the fourth quarter of 2025, net sales grew organically by 2.6%, while reported net sales declined by 3.1% compared with the year-earlier quarter. The company’s full-year EBITDA pre grew organically by 5.6% to € 6.1 billion. Foreign exchange had a negative effect of –5.0% while portfolio effects offset each other at 0.0%. The EBITDA pre margin improved by 0.2 percentage points to 28.9%. In the fourth quarter, reported EBITDA pre was down 3.2% while growing 3.1% organically. For the full year, earnings per share pre were € 8.34 (2024: € 8.63). The Executive Board and Supervisory Board will propose an unchanged dividend of € 2.20 per share to the Annual General Meeting on April 24, 2026. This would mark the fifteenth year in a row with an increasing or stable dividend. Merck KGaA, Darmstadt, Germany agreed with the U.S. administration to expand access to its portfolio of in vitro fertilization therapies in the United States. The company is also filing Pergoveris for expedited review under the U.S. Food and Drug Administration Commissioner’s National Priority Voucher program. Furthermore, the Group has reached an agreement with the U.S. Department of Commerce to be relieved from Section 232 pharmaceutical tariffs and has committed to further invest in the U.S. Outlook for 2026 For 2026, Merck KGaA, Darmstadt, Germany anticipates net sales between € 20.0 billion and € 21.1 billion and EBITDA pre between € 5.5 billion and € 6.0 billion. This corresponds to an organic net sales development of –1% to +2% and an organic EBITDA pre development of –4% to +1%. Foreign exchange effects are expected to have an influence of –4% to –2% on net sales and –7% to –3% on EBITDA pre. Overall, this translates to an expected EPS pre range of € 7.10 to € 8.00. This guidance assumes no U.S. sales of Mavenclad from March 2026 amid generic competition. It also excludes positive effects from a potential U.S. launch of Pergoveris. Life Science: Process Solutions drives return to growth The Process Solutions business unit powered growth in Life Science throughout the year, delivering four consecutive quarters of around 10% organic sales growth. Life Science net sales reached € 9.0 billion, with organic growth of 4.0% and portfolio effects of 0.1% dampened by foreign exchange effects of –3.4%. EBITDA pre remained around stable at € 2.6 billion. Organic growth of 3.9% was impacted by foreign exchange effects of –4.3%. Process Solutions, which markets solutions for the entire pharmaceutical production value chain, grew organically across its entire portfolio and in all regions. This growth was supported by demand for bioprocessing solutions and novel modalities such as antibody-drug conjugates. Driven primarily by higher demand from new customer projects and a normalizing market, net sales in Process Solutions grew organically by 10.7% year-on-year to € 3.8 billion. Order intake remains strong, with the book-to-bill ratio comfortably above 1. The business unit is strategically well positioned to capture market momentum and opportunities arising from the industry’s shift toward biologics. Science & Lab Solutions posted organic growth of 0.3% and positive portfolio effects of 0.2%. These were impacted by foreign exchange effects of –3.4%, resulting in net sales of € 4.5 billion. The business unit’s portfolio comprises products and services for pharmaceutical, biotechnology and academic research. Impacts during the year included the effects of U.S. policy changes and the extended government shutdown on spending by academic and government labs as well as ongoing challenges in the market environment, especially in China. Additionally, early-stage biotech funding remained flat. This resulted in lower demand for laboratory products. Net sales in Life Science Services were impacted by non-repeating business from the previous year and came in at € 659 million in 2025. As of January 1, 2026, Life Science has transformed its business units to align its go-to-market approaches even more closely with specific customer experiences. Healthcare: Rare Diseases franchise underpins growth profile Healthcare had a solid year across franchises, with net sales in the business sector growing organically by 3.7% to € 8.6 billion in fiscal 2025. Portfolio effects from the acquisition of SpringWorks added growth of 2.2% while foreign exchange had an impact of –4.1%. EBITDA pre recorded an organic increase of 11.5%. Negative impacts resulted from foreign exchange effects of –8.5% and a minor portfolio effect of –0.1%. Overall, EBITDA pre increased to € 3.1 billion. The newly established Rare Diseases franchise contributed significantly to the results as of the third quarter of 2025, reflected as a portfolio effect. It includes sales from Ogsiveo, which treats progressing desmoid tumors, and Gomekli/Ezmekly, approved for plexiform neurofibromas associated with neurofibromatosis type 1. Merck KGaA, Darmstadt, Germany gained the worldwide rights for these products following the acquisition of SpringWorks. Together with pimicotinib as a systemic treatment for patients with tenosynovial giant cell tumor, the company’s Rare Diseases franchise is expected to contribute to organic growth throughout 2026. The Cardiovascular, Metabolism & Endocrinology (CM&E) franchise was the largest growth driver in Healthcare, posting organic year-on-year growth of 7.3% across all therapeutic areas. The franchise includes the diabetes medicine Glucophage, the beta-blocker Concor, the thyroid medicine Euthyrox, and Saizen, which is primarily used to treat growth hormone disorders. Net sales in the Neurology & Immunology (N&I) franchise increased by 1.9% organically compared with the previous year. Mavenclad, indicated for relapsing forms of multiple sclerosis, delivered organic growth of 16.6% and net sales of € 1.2 billion. This was driven primarily by increasing demand in North America and Europe. Rebif, also for relapsing forms of multiple sclerosis, saw net sales decline organically by 23.0% as expected. In the Oncology franchise, organic net sales growth was 0.3%. Erbitux, a treatment for metastatic colorectal cancer and for cancer of the head and neck, grew organically by 6.6% amid a challenging competitive environment in China. Due to strong competition, net sales for Bavencio, which is used to treat locally advanced or metastatic urothelial carcinoma, declined organically by 13.8%. Net sales of the Fertility franchise remained around stable, with organic growth of 0.4% in 2025. Gonal-f, a follicle-stimulating hormone treatment for infertility, declined organically by 6.7%. Pergoveris, indicated for the stimulation of follicular development in women, grew organically by 22.6% across all regions. Electronics: Semiconductor Materials delivers sustained growth momentum The artificial intelligence (AI) boom sustained strong demand in Electronics. The Semiconductor Materials business was the business sector’s main growth engine, delivering high single-digit organic growth for the year and the eighth consecutive quarter of strong year-on-year growth. Delivery Systems & Services (DS&S) recorded an organic decline in net sales caused by prolonged delays to large customer projects. This was the main driver behind the 0.6% organic decline in net sales of Electronics in 2025. The divestment of Surface Solutions led to a portfolio effect of –3.2% despite a positive contribution from the acquisition of Unity-SC. Foreign exchange effects were –3.3%. Overall, net sales declined to € 3.5 billion. EBITDA pre decreased 14.1% year-on-year to € 833 million. One-time effects in the second quarter of 2025 and lower sales in DS&S more than offset the growth of Semiconductor Materials. Organic performance decreased by 9.0%. Foreign exchange and portfolio effects had a negative impact of –4.4% and –0.7% respectively. Net sales of Semiconductor Solutions declined organically by 1.4% to € 2.5 billion. Semiconductor Materials achieved strong organic sales growth driven by the demand for high-value materials that enable AI chip systems and advanced nodes. Advanced nodes are the latest semiconductor manufacturing processes that enable smaller feature sizes and the most powerful chips. DS&S recorded a sales decline in the double-digit percentage range. The company expects the business to stabilize in 2026 and to return to growth in the medium term. Optronics delivered net sales of € 772 million. The business unit comprises the businesses with liquid crystals, photoresists for display applications, OLED materials, and metrology and inspection equipment for semiconductor and optoelectronic manufacturing. The overall increase of 3.2% came on the back of organic growth of 0.6% and portfolio effects of 5.8% from the acquisition of Unity-SC. With the divestment of Surface Solutions, which closed at the end of July 2025, Electronics has transformed into a pure-play business with a primary focus on the semiconductor market. Company drives forward science and technology Merck KGaA, Darmstadt, Germany made significant strides in science and technology. In Life Science, the acquisition of HUB Organoids further strengthens its position in next-generation biology. Organoids are a key resource for researchers, leveraging 3D cell cultures to generate earlier, more predictive insights and in turn supporting more informed decisions throughout drug development. Additionally, the partnership with imec is aimed at developing microfluidic devices that simulate the functions of human organs using living cells. This collaboration combines the expertise of Merck KGaA, Darmstadt, Germany in cells and organs with imec’s advanced sensor technology, providing scientists with critical insights into cellular responses to medications. The company also invested € 500 million in its Semiconductor Solutions mega-site in Kaohsiung, Taiwan. This site focuses on semiconductor materials, especially thin films – a technology that allows materials to be deposited and removed on an atomic level, enabling more layers, higher complexity and new chip architectures essential for advanced semiconductors. Regarding its sustainability ambition, Merck KGaA, Darmstadt, Germany exceeded its climate target to halve absolute Scope 1 (direct) and Scope 2 (indirect) greenhouse gas emissions by 2030. The company achieved a 60% reduction compared with the 2020 baseline at the end of 2025 – five years ahead of schedule. This is a major milestone toward the company’s goal of achieving climate neutrality by 2040. Overview of the key figures Group Key figures Change € million 2025 2024 € million % Net sales 21,102 21,156 -54 -0.3% Operating result (EBIT)1 3,601 3,645 -44 -1.2% Margin (% of net sales)1 17.1% 17.2% EBITDA2 5,899 5,779 120 2.1% Margin (% of net sales)1 28.0% 27.3% EBITDA pre1 6,109 6,072 37 0.6% Margin (% of net sales)1 28.9% 28.7% Profit after tax 2,615 2,786 -171 -6.1% Earnings per share (€) 6.00 6.39 -0.39 -6.1% Earnings per share pre (€)1 8.34 8.63 -0.29 -3.4% Operating cash flow 3,932 4,586 -654 -14.3% 1 Not defined by IFRS Accounting Standards. 2 Not defined by IFRS Accounting Standards; EBITDA corresponds to operating result (EBIT) adjusted by depreciation, amortization, impairment losses, and reversals of impairment losses. Group Net sales by business sector € million 2025 Share Organic growth1 Exchange rate effects1 Acquisitions/ divestments1 Total change 2024 Share Life Science 8,980 42% 4.0% -3.4% 0.1% 0.7% 8,916 42% Healthcare 8,607 41% 3.7% -4.1% 2.2% 1.8% 8,455 40% Electronics 3,515 17% -0.6% -3.3% -3.2% -7.1% 3,785 18% Group 21,102 100% 3.1% -3.7% 0.4% -0.3% 21,156 100% 1 Not defined by IFRS Accounting Standards. Life Science Net sales by business unit € million 2025 Share Organic growth1 Exchange rate effects1 Acquisitions/ divestments1 Total change 20242 Share Science & Lab Solutions 4,536 51% 0.3% -3.4% 0.2% -2.9% 4,672 52% Process Solutions 3,785 42% 10.7% -3.5% 0.3% 7.5% 3,522 40% Life Science Services 659 7% -4.5% -3.4% -0.9% -8.7% 722 8% Life Science 8,980 100% 4.0% -3.4% 0.1% 0.7% 8,916 100% 1 Not defined by IFRS Accounting Standards. 2 Previous-year figures have been adjusted owing to an internal realignment. Healthcare Net sales by major product lines/products € million 2025 Share Organic growth1 Exchange rate effects1 Acquisitions/ divestments1 Total change1 2024 Share Oncology 1,926 22% 0.3% -4.5% – -4.2% 2,009 24% thereof: Erbitux® 1,176 14% 6.6% -5.5% – 1.2% 1,162 14% thereof: Bavencio® 612 7% -13.8% -2.9% – -16.7% 735 9% Rare Diseases 188 3% thereof: Ogsiveo® 134 2% thereof: Gomekli® 55 1% Neurology & Immunology 1,659 19% 1.9% -3.6% – -1.7% 1,688 20% thereof: Mavenclad® 1,194 14% 16.6% -4.1% – 12.4% 1,062 13% thereof: Rebif® 465 5% -23.0% -2.8% – -25.8% 626 7% Fertility 1,457 17% 0.4% -5.1% – -4.6% 1,528 18% thereof: Gonal-f® 735 9% -6.7% -5.0% – -11.7% 833 10% thereof: Pergoveris® 329 4% 22.6% -5.2% – 17.4% 280 3% Cardiovascular, Metabolism & Endocrinology 3,050 35% 7.3% -3.8% – 3.4% 2,949 35% thereof: Glucophage® 975 11% 5.9% -3.7% – 2.3% 954 11% thereof: Concor® 625 7% 4.7% -2.3% – 2.4% 611 7% thereof: Euthyrox® 653 8% 9.4% -3.9% – 5.4% 619 7% thereof: Saizen® 388 5% 13.0% -6.8% – 6.2% 366 4% Other 328 4% 280 3% Healthcare 8,607 100% 3.7% -4.1% 2.2% 1.8% 8,455 100% 1 Not defined by IFRS Accounting Standards. Electronics Net sales by business unit € million 2025 Share Organic growth¹ Exchange rate effects1 Acquisitions/ divestments1 Total change 2024 Share Semiconductor Solutions 2,494 71% -1.4% -3.7% -0.1% -5.2% 2,631 69% Optronics 772 22% 0.6% -3.2% 5.8% 3.2% 748 20% Surface Solutions 249 7% 1.9% -1.3% -39.5% -38.8% 406 11% Electronics 3,515 100% -0.6% -3.3% -3.2% -7.1% 3,785 100% 1 Not defined by IFRS Accounting Standards. Report on expected developments € million Net sales EBITDA pre1 Free cash flow Group • ~20,000 to 21,100 • Organic -1% to +2% • Foreign exchange effect -4% to -2% • Portfolio ~0% • ~5,500 to 6,000 • Organic -4% to +1% • Foreign exchange effect -7% to -3% • Portfolio ~0% • ~1,500 to 2,000 Life Science • ~8,900 to 9,300 • Organic +3% to +6% • Foreign exchange effect -4% to -1% • Portfolio ~0% • ~2,500 to 2,700 • Organic +2% to +6% • Foreign exchange effect -4% to -1% • Portfolio ~+1% Healthcare • ~7,900 to 8,300 • Organic -7% to -4% • Foreign exchange effect -4% to -1% • Portfolio ~+2% • ~2,500 to 2,700 • Organic -14% to -10% • Foreign exchange effect -6% to -3% • Portfolio ~0% Electronics • ~3,200 to 3,400 • Organic +3% to +7% • Foreign exchange effect -5% to -2% • Portfolio ~-7% • ~900 to 1,000 • Organic +21% to +27% • Foreign exchange effect -7% to -4% • Portfolio ~-4% Corporate and Other • ~ -450 1 Not defined by IFRS Accounting Standards; EBITDA corresponds to operating result (EBIT) adjusted by depreciation, amortization, impairment losses, and reversals of impairment losses. EPS pre € 7.10 to € 8.00, based on an underlying tax rate of 22%. Notes to editors: The press conference for media representatives will take place at 10:00 a.m. CET. The respective presentation and further information for journalists, including a digital press kit, can be found here. The annual report 2025 can be found here. Merck KGaA, Darmstadt, Germany on LinkedIn. Company photos and videos can be found here. Merck KGaA, Darmstadt, Germany stock symbols: Reuters: MRCG, Bloomberg: MRK GY, Dow Jones: MRK.DE Frankfurt Stock Exchange: ISIN: DE 000 659 9905 – WKN: 659 990

编者按：多发性硬化（MS）是一种致残性自身免疫性中枢神经系统疾病。根据世界卫生组织官网数据，全球MS患者超过了180万。过去十多年间，多款疗法获监管机构批准治疗MS，极大改善了患者的生存状况。同时，全球目前还有一系列针对MS的研发管线正在持续推进，旨在为患者提供更好的治疗选择。作为全球医药创新的赋能者，药明康德一直以来依托“一体化、端到端”的CRDMO赋能平台，助力全球合作伙伴，推进包括MS在内各类疾病的创新疗法开发，加速造福病患。 多发性硬化（MS）是一种终身进展的中枢神经系统自身免疫病，迄今还没有治愈手段。该病多见于中青年群体，女性患病率更高。MS的核心病理是免疫系统错误攻击包裹神经纤维的髓鞘，使其不断受损、脱落，进而影响大脑、脊髓及视神经的正常传导功能。MS会导致患者的行动能力与认知功能逐渐下降。 根据病程特点，多发性硬化可分为四种类型：复发缓解型（RRMS）、继发进展型（SPMS）、原发进展型（PPMS）和进展复发型（PRMS）。其中RRMS最为常见，疾病常呈周期性复发与缓解，但每次缓解可能并不完全，残留症状会逐渐累积。RRMS患者有约四分之一在确诊10年内进展为SPMS，随着时间推移这一比例将更高。一旦进入SPMS阶段，症状多呈持续恶化趋势，患者逐渐丧失生活自理能力，甚至面临视力丧失和生命威胁。 图片来源：123RF 从19世纪到20世纪上半叶，科学界逐渐揭示MS的神经病学本质和其背后的免疫异常机制。20世纪50年代，科学家发现可的松等糖皮质激素能够缓解MS急性发作，但无法长期阻止疾病进展。 直到上世纪90年代，首批能够在缓解期控制病情的免疫调节剂问世，标志着“疾病修正疗法”时代的开启。随后，不同靶点、不同机制的疾病修正疗法相继出现，让控制MS进展成为了可能。过去十余年，更多新型疗法的不断诞生进一步改善了患者的长期预后。这篇文章也将回望近些年来多发性硬化创新疗法的发展历程。 传统免疫调节注射疗法 20世纪80年代末，研究者逐渐认识到异常的免疫攻击在多发性硬化病程恶化中发挥关键作用，于是开始探索各种免疫调节策略的治疗潜力。 重组人干扰素-β-1b（IFN-β-1b）首先成为突破口。临床研究显示，它能显著延缓复发缓解型多发性硬化（RRMS）的自然进展，使患者在两年内的复发次数减少约34%。1993年7月，IFN-β-1b（商品名Betaseron）获FDA批准，成为能够真正改变RRMS病程的治疗手段。2022年，同类药物干扰素-β-1a（商品名Rebif）获批，其既能降低复发频率，还可延缓持续性残疾的出现。2014年，Rebif的升级版本——聚乙二醇化干扰素-β-1a（peginterferon-β-1a，商品名Plegridy）获FDA批准，延长了体内作用时间，从而降低给药频率，提高患者的长期依从性。 图片来源：123RF 除干扰素外，格拉替雷（glatiramer，商品名Copaxone）也是早期注射型免疫调节剂之一。它由四种氨基酸构成的多肽混合物组成，能够竞争性阻断免疫细胞与髓磷脂的异常相互作用，从而发挥保护作用。该药于1996年获FDA批准，用于RRMS的长期治疗。 这些注射疗法的成功标志着MS治疗从单纯缓解症状迈向真正能够改变病程的疾病修正治疗阶段。这类传统免疫调节剂至今仍是MS治疗体系中的重要基石。 生物制剂靶向疗法问世 传统免疫调节注射疗法改变了MS的治疗格局，但仍有约三分之一的患者几乎无应答。为了让更多患者获益，科研界和产业界开始探索生物制剂靶向疗法。 由Athena Neuroscience、Elan与渤健合作开发的natalizumab，是首个获批用于MS治疗的生物制剂类靶向药物。它的出现，源于一次“误打误撞”的研究发现。 20世纪90年代，斯坦福大学斯坦曼实验室与Athena Neuroscience的泰德·耶德诺克（Ted Yednock）博士团队合作，希望了解MS的关键病理环节之一——淋巴细胞如何穿透血脑屏障。在动物实验中，他们意外发现一种“推波助澜”的分子——α4β1整合素，它能帮助淋巴细胞越过血脑屏障，引发大脑炎症。更令人惊喜的是，相应的抗体能够抑制这种异常浸润。 图片来源：123RF 意识到这项发现的突破性意义后，团队迅速调整方向，研发出针对这一靶点的人源化单抗natalizumab。凭借出色的临床数据，Tysabri（natalizumab，那他珠单抗）在2004年获FDA批准上市，用于RRMS的治疗。 长期随访数据进一步证实了其疗效：治疗两年后，与安慰剂相比，患者的残疾持续进展风险下降42%-54%，年复发率下降68%。 2014年，另一款靶向CD52的Lemtrada（alemtuzumab，阿仑单抗）也获批用于MS治疗。这一药物早在20世纪90年代末就已在少量患者中展现出抑制大脑新发炎症与减少复发的潜力。然而，尽管炎症减少，大多数患者仍表现出疾病进展，这一矛盾曾让研究团队困惑不已。 多年研究后，谜底终于揭晓：在MS的病程中，“炎症”与“退行性神经损伤”是相互关联但又相对独立的两条病理轨迹。MS的发作会引发炎症，同时累积神经损害；当损害达到一定程度后，即便炎症消退，退行性进展也会继续，就像滚下雪坡的雪球很难停止。因此，研究者推断：要让alemtuzumab发挥最大价值，需要尽可能在疾病早期使用。 后续的临床研究显示，接受alemtuzumab治疗三年后，患者年复发率下降74%，持续残疾累积风险下降71%，残疾评分也明显改善。最终，这款药物获得FDA批准，为RRMS患者带来了新的选择。 自2016年起，多款靶向CD20的单克隆抗体陆续获FDA批准，包括：Ocrevus（ocrelizumab，奥瑞利珠单抗）；Kesimpta（ofatumumab，奥法妥木单抗）；Briumvi（ublituximab，乌妥昔单抗）等。其中，奥瑞利珠单抗是FDA批准的首个用于PPMS的创新疗法。PPMS占MS患者的约10%，没有明显缓解期，残疾累积更快，生活质量常受严重影响。 长期随访数据显示，经过奥瑞利珠单抗治疗11年后，PPSM患者中有33%的患者无残疾进展、80%的人无需依赖轮椅（部分患者可能需要比轮椅更简单的助行器）。相比大多数MS生物制剂每月1次的用药频率，这款药物只需半年输注1次，提高了患者的依从性。 小分子疗法接力治疗 在相当长的时间内，获批上市的MS疗法往往需要注射治疗。因此，科学家们也在寻找用药更便捷的小分子口服药物，作用机制各异的小分子疗法由此诞生。 2010年1月，达伐吡啶（dalfampridine，商品名：Ampyra）正式获FDA批准，成为首个用于MS的口服药物。它是一种钾通道阻滞剂，通过改善脱髓鞘神经纤维的信号传导，帮助患者缓解步行能力下降这一最常见的功能障碍。临床研究显示，约三分之一的患者在服用达伐吡啶后步行速度明显提升，部分患者甚至能接近恢复正常步态。 另外，特立氟胺（teriflunomide，商品名：Aubagio）通过抑制二氢乳清酸脱氢酶来抑制活化T/B细胞的增殖，但保留正常免疫反应；富马酸二甲酯（dimethyl fumarate，商品名：Tecfidera）及其升级版本富马酸地洛西美（diroximel fumarate，商品名：Vumerity）则通过激活Nrf2通路发挥免疫调节及细胞保护作用。 其中，S1P受体调节剂因靶点明确、疗效突出而成为一类重要的小分子疗法。2010年9月，芬戈莫德（fingolimod，商品名：Gilenya）获FDA批准，成为可显著降低MS复发率的口服疗法。它通过与淋巴细胞表面的S1P受体结合，使其滞留在淋巴结，从而减轻中枢神经系统的炎症。长期临床试验表明，使用芬戈莫德治疗10年后，46%的患者无复发。 芬戈莫德的升级产品——第二代选择性S1P受体调节剂西尼莫德（siponimod）对S1P受体中的特定亚型S1P1、S1P5具有高度的选择性。它通过与二者的结合，既能阻止淋巴细胞进入中枢神经系统、降低炎症反应，还能穿透血脑屏障、促进髓鞘再生，起到神经修复作用。 更多新研究助力MS治疗 尽管现有疗法在治疗MS方面已显示出疗效，然而由于血脑屏障的存在，它们在清除中枢神经系统中的浆细胞方面效果有限。而科学家正考虑借助嵌合抗原受体T细胞（CAR-T）技术，来帮助解决这一难题。 今年，一项《细胞》研究证实了靶向B细胞成熟抗原的CAR-T疗法在治疗进展型多发性硬化（PMS）中的安全性和有效性。据介绍，共有5名PMS患者参与了1期临床试验，他们接受了抗BCMA CAR-T细胞疗法。结果，患者中枢神经系统中的浆细胞减少。在随访时间最长为9个月的病例队列中，观察到了显著的功能改善。此外，治疗还减轻了患者脑脊液中的小胶质细胞活化。 今年的另一项《细胞》研究指出，在MS患者的神经元中，干扰素-γ（IFNγ）会诱导免疫蛋白酶体亚基PSMB8的表达，导致代谢关键酶PFKFB3积累，进而引发炎症和神经退行性病变。而抑制这两种分子，能够在小鼠中改善MS症状，从而为MS治疗提供了新的靶点。 如今，产业界也在不断探索，致力于为患者带来更安全、有效、便利的治疗选择。过去25年间，FDA共批准了至少15款治疗MS的新疗法。当前，有近80款针对MS的新疗法正处于积极的临床研究中，其中数款疗法已进入3期临床阶段，涵盖布鲁顿酪氨酸激酶（BTK）抑制剂、CD40L靶向单抗、CD19靶向双抗等。 作为全球医药创新的赋能者，药明康德在过去25年发展历程中，很荣幸为其中一些获批疗法或在研疗法提供赋能，通过“一体化、端到端”的CRDMO赋能平台，助力全球合作伙伴加速创新疗法的研发进程、从而早日造福病患。 在对抗MS的漫漫征途中，科学家数十年如一日的追寻带来了一款又一款的MS疗法。我们也期待，在未来能见证更多创新疗法的问世，帮助更多患者开启生命的新篇章。 参考资料： [1] Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf.  Retrieved Oct 20, 2025 from https://www.msif.org/wp-content/uploads/2020/10/Atlas-3rd-Edition-Epidemiology-report-EN-updated-30-9-20.pdf [2] History of Multiple Sclerosis | MSAA. Retrieved Oct 20, 2025 from https://mymsaa.org/ms-information/overview/history/ [3] Ransohoff, R. M., Hafler, D. A., & Lucchinetti, C. F. (2015). Multiple sclerosis—a quiet revolution. Nature Reviews Neurology, 11(3), 134-142. doi: 10.1038 / nrneurol.2015.14 [4] Lublin, F. (2005). History of modern multiple sclerosis therapy. Journal of Neurology, 252(Suppl 3), iii3-iii9. https://doi.org/10.1007/s00415-005-2010-6 [5] Treatment of Multiple Sclerosis. Retrieved Oct 20, 2025 from  https://www.nature.com/collections/whyfzwfvvr/timeline/ 欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。 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。 更多推荐 点个“在看”再走吧~