This is a multicenter, observational study for patients with a confirmed diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as TPP1 deficiency, who intend to be or are currently being treated with cerliponase alfa. Patients receiving or expected to receive cerliponase alfa within 60 days of signing the informed consent form (ICF) may be eligible to enroll in the study, assuming all regulatory requirements for sites that have agreed to participate and protocol inclusion criteria are met. Data may be collected for all or some of the assessments as outlined in the protocol, dependent upon the clinic's and/or individual patient's standard of care.

开始日期2020-08-19

申办/合作机构

BioMarin Pharmaceutical, Inc.

NCT03862274

/ Enrolling by invitationN/AIIT

Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease

The investigators propose a study to assess cognitive and developmental outcomes of patients with CLN2 that are untreated and receiving cerliponase alfa. This study aims to validate standardized assessment measures to establish a standard of care. The secondary aim is to compare cognitive and developmental outcomes of patients with CLN2 that are receiving celiponase alfa to a natural history cohort. To accomplish specific aims of the study, the investigators will use a multi-method approach to collect retrospective data collected as standard of care and prospective developmental data in children with CLN2 disease. The investigators will use a combination of standardized measures that include direct assessment and parent report of child development. The investigators focus will also include multiple measures of development including language, motor, social-emotional, and adaptive functioning.

开始日期2018-12-01

申办/合作机构

Nationwide Children's Hospital

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100 项与阿尔法脂肪酶相关的临床结果

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100 项与阿尔法脂肪酶相关的转化医学

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100 项与阿尔法脂肪酶相关的专利（医药）

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项与阿尔法脂肪酶相关的文献（医药）

2026-03-01·JOURNAL OF CHILD NEUROLOGY

Treatment of Neuronal Ceroid Lipofuscinosis Type 2 with Cerliponase Alfa: A Systematic Review and Single-Arm Meta-Analysis of Two Studies

Review

作者: de Jesus, Ana Clara Fonseca Souza ; Qadri, Maria ; Oliveira, Juliana Almeida ; Shahid, Fatima ; Saddique, Muhammad Nabeel ; Sarmento, Filipe Pereira

Background: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disorder caused by CLN2 gene mutations, leading to ceroid lipofuscin accumulation and progressive neurodegeneration. Cerliponase alfa, a recombinant tripeptidyl peptidase-1, may improve aspects of disease progression, but common hypersensitivity and infusion reactions, along with a limited number of studies and lack of controlled trials, constrain the generalizability of these findings. Purpose: This systematic review and single-arm meta-analysis aims to evaluate the efficacy and safety of cerliponase alfa in treating children with CLN2. Methods: Following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the protocol was registered in PROSPERO (CRD42024541000). We included prospective and retrospective cohorts of CLN2 patients treated with cerliponase alfa. A comprehensive search was conducted in PubMed, Embase, and Cochrane Central up to February 2024. Clinical outcomes and adverse effects were analyzed using a random effects model to compute pooled proportions with 95% CIs. Study quality was assessed with the Cochrane Risk of Bias tool for Non-randomized Studies. Results: From 318 records, 3 observational studies with 55 patients were included. A Clinical Rating Scale score of 0 or 1 was seen in 24% of patients. Generalized tonic-clonic seizures occurred in 41%, and dystonia in 15%. Adverse events included pyrexia (60%), hypersensitivity (82.6%), anaphylaxis (3%), and infusion-associated reactions (18.31%). Significant heterogeneity was observed. Conclusion: Cerliponase alfa may improve clinical outcomes in children with CLN2, though adverse effects might be prevalent.

2026-01-01·JOURNAL OF INHERITED METABOLIC DISEASE

Natural‐History Mapping of Lysosomal Storage Disorders ( LSDs ): Gaucher Disease as a Model for Precision Care

Review

作者: Vaishnaw, Maya ; Mistry, Pramod. K. ; Ain, Noor Ul

ABSTRACT:

Natural‐history datasets have become pivotal for drug development and for shaping clinical‐practice guidelines in rare diseases, yet many lysosomal storage disorders would benefit from deep phenotyping and modern analytic methods. Our objective was to integrate the past decade of genomic, cellular, treatment‐outcome, and regulatory advances into a practical framework for capturing and interpreting natural‐history data, using Gaucher disease (GD) as a paradigm. We reviewed more than 300 peer‐reviewed articles (2005–2025), FDA guidance documents, and output from large real‐world registries. Particular attention was paid to long‐read GBA sequencing, biomarkers such as lyso‐Gb1, emerging newborn screening programs, and preliminary observational work that points toward multi‐state disease modeling. Key observations include: (i) Whole‐gene sequencing has expanded genotype–phenotype maps, revealing more than 70 recombinant GBA alleles that confound panel tests; (ii) registry trajectories suggest that formal multi‐state models could capture treatment‐modified courses and silent endpoints—monoclonal gammopathy, malignancy, Parkinson's disease, pulmonary arterial hypertension—better than current summary statistics; (iii) lyso‐Gb1 outperforms legacy biomarkers and now serves as a second‐tier newborn‐screening marker; (iv) Robust natural‐history evidence has already underpinned regulatory approvals across several lysosomal disorders—including olipudase alfa for ASMD, cerliponase alfa for CLN2, vestronidase alfa for MPS VII, and sebelipase alfa for infantile‐onset LAL‐D—demonstrating that well‐curated registries can serve as viable external controls for future LSD submissions. The convergence of deep phenotyping, genotype‐aware analytics, and systematic biomarker capture promises to transform natural‐history registries from descriptive archives into predictive engines. Gaucher disease offers a working template that, when extended across the LSD spectrum, can accelerate precision care and the development of next‐generation therapeutics.Trial Registration:ClinicalTrials.gov identifier: NCT00358943, NCT03291223.

2025-12-01·CHILDS NERVOUS SYSTEM

Novel surgical approach for intraventricular cerliponase alfa enzyme replacement therapy via central venous access device (CVAD) port in neuronal ceroid lipofuscinosis type 2 (CLN2) disease

Article

作者: Goldstein, Hannah E ; Barrios-Anderson, Adriel ; Nistal, Dominic ; Chang, Irene J ; Boop, Scott ; Cherny, W Bruce ; Shelkowitz, Emily ; Kho, Terry ; Hauptman, Jason

INTRODUCTION:

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a genetic disease caused by deficiency of the enzyme tripeptidyl peptidase 1 (TPP1), resulting in seizures, vision/cognitive decline, and early death. Cerliponase alfa is an enzyme replacement therapy approved as treatment for CLN2 disease, administered by intracerebroventricular infusion via a surgically implanted device. Maintaining sterility for prolonged scalp-based infusions can be difficult in children and damage devices. We report the development of a technique connecting the intraventricular device and catheter to a chest port to mitigate some of these challenges.

METHODS:

We describe a seven-patient cohort who underwent implantation of our modified infusion system connecting a ventricular catheter distally to a central venous access device (CVAD) port implanted in the anterior chest.

RESULTS:

Between March 2019 and April 2024, seven (n = 7) patients aged 2-19 years underwent the placement of this system or had an old device converted to a CVAD port system. None of our patients has experienced significant access issues, infection, or required revision since implantation.

CONCLUSIONS:

The use of an intraventricular access device connected to a CVAD allows for safe and efficacious long-term infusion of cerliponase alfa therapy and provides a more stable and well-tolerated alternative to scalp-based infusions.

项与阿尔法脂肪酶相关的新闻（医药）

2026-03-18

·allsci.com

Polaryx takes FDA Fast Track Designation for PPARα agonist targeting rare CLN2 disease

Polaryx Therapeutics, Inc. (Nasdaq: PLYX), a clinical-stage biotechnology company headquartered in New Jersey, announced receipt of US FDA Fast Track Designation for PLX-200, an oral small molecule peroxisome proliferator-activated receptor alpha (PPARα) agonist comprised of gemfibrozil, for the treatment of Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL/CLN2 disease). The fast-track status enables more frequent FDA interactions and eligibility for rolling review of a future marketing application. PLX-200 previously received Rare Pediatric Disease Designation for CLN2 disease and Orphan Drug Designation for Neuronal Ceroid Lipofuscinosis from the FDA. PLX-200 is being advanced through SOTERIA, a Phase II, open-label, single-arm basket trial designed to evaluate safety, tolerability, and clinical activity across four lysosomal storage disorders: CLN2, CLN3, Krabbe disease, and Sandhoff disease. Polaryx received a safe-to-proceed letter from the FDA in October 2025 and plans to initiate SOTERIA in Q3 2026 at sites in the United States, Europe, and Asia. For the CLN2 and CLN3 cohorts, the trial will incorporate analyses comparing treated patients against natural history data as a control arm. No NCT identifier for SOTERIA was disclosed in the company’s announcement. Gemfibrozil itself holds longstanding FDA approval as a lipid-regulating agent for adults with hypertriglyceridemia, marketed as Lopid since 1981, but has not previously been approved for pediatric or neurological indications. Research context CLN2 disease is a rare, autosomal recessive neurodegenerative disorder caused by deficiency of the lysosomal enzyme tripeptidyl peptidase 1. Onset typically occurs between ages two and four, with rapid progression of seizures, language loss, motor decline, and vision impairment, leading to death in adolescence. The only approved disease-modifying therapy is cerliponase alfa (Brineura), a recombinant enzyme replacement therapy administered via intracerebroventricular infusion every two weeks. While cerliponase alfa has been shown to slow functional decline and improve survival, it does not halt disease progression and requires invasive delivery through a surgically implanted reservoir. Delayed diagnosis remains a documented barrier to treatment effectiveness, as neurodegeneration is already advanced by the time many patients begin therapy. PLX-200 differs from cerliponase alfa in both modality and route of administration. Where cerliponase alfa delivers recombinant enzyme directly into the central nervous system through biweekly intracerebroventricular infusions, PLX-200 is an oral small molecule whose active ingredient, gemfibrozil, has documented ability to cross the blood-brain barrier in preclinical studies. Rather than replacing a single deficient enzyme, PLX-200 acts as a PPARα agonist with a mechanism that Polaryx states addresses lysosomal dysfunction, neuroinflammation, and neuronal loss across multiple lysosomal storage disorders. This broader mechanism underlies the basket trial design of SOTERIA, which enrolls patients with four distinct conditions. The oral route could reduce the procedural burden associated with current CLN2 disease treatment, though no clinical efficacy data for PLX-200 in any lysosomal storage disorder have been reported to date. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

快速通道孤儿药临床2期上市批准

2026-02-28

·BiG生物创新社

抗癫痫药物百年演进：从偶然发现到精准治疗的未来图景

图1 秦兵教授，暨南大学附属第一医院癫痫中心主任 2025年12月，BiG联合湾有引力（光明生物医药创新中心），在深圳隆重举办的“BiG冬季论坛｜CNS领域的下一个黄金时代”专题研讨会，本次研讨会盛况空前，来自学术界、顶尖医院、知名药企、头部投资机构的数百位专家与同仁汇聚一堂，围绕CNS药物研发这一充满挑战与机遇的领域，展开了密集而深入的头脑风暴。在抗癫痫药物研发领域，暨南大学附属第一医院癫痫中心主任秦兵教授的专题报告《抗癫痫药物的过去、现在和未来》引发了广泛关注。秦兵教授基于其深厚的学术积淀与临床经验，系统梳理了抗癫痫药物（Antiepileptic Drugs, AEDs）从偶然发现到精准研发的百年演进历程，深入剖析了当前药物研发格局与未来发展方向，为行业从业者和投资者提供了极具价值的专业洞察力。 01 癫痫疾病的流行病学特征与治疗现状癫痫作为神经系统重大慢性疾病，全球患者规模近7000万人，中国患者约1000万，国内外患病率基本相当。流行病学数据显示，癫痫发病呈现显著的双峰特征：婴幼儿期与老年期为两大高发人群。值得注意的是，癫痫患者意外死亡风险较正常人群高出2-3倍，凸显了该疾病沉重的公共卫生负担。目前国际公认的癫痫治疗方法包括四种核心手段： 1.药物治疗：覆盖100%癫痫患者，是基础性治疗方式； 2.手术或神经调控治疗：适用于影像学有明确致痫灶的患者； 3.生酮饮食疗法：在特定小儿癫痫综合征患者中可取得显著疗效； 4.激素治疗：主要针对难治性癫痫脑病伴持续性痫性放电的婴幼儿患者。需要明确的是，中医、埋线、针灸等替代疗法均无效。药物治疗的有效性数据来自一项具有里程碑意义的30年纵向队列研究。该研究对连续抗癫痫药物治疗方案1年无发作率进行分析，结果显示：首次单药治疗可使46%患者在1年内达到无发作；当第一种药物无效更换第二种药物时，无发作比例仅增加11%；第三种药物再增加4%；后续更换药物的叠加有效率降至1%以下。这一数据清晰地揭示了药物难治性癫痫的现实困境——约30%患者经多种药物治疗后仍无法有效控制发作。 02 抗癫痫药物发展的三大里程碑事件与新药研发格局抗癫痫药物研发史可划分为三个里程碑事件： 1875年：英国医生偶然发现溴化物具有抗癫痫疗效，开启现代药物治疗癫痫的先河； 1912年：德国医生偶然发现苯巴比妥（Luminal）的抗癫痫作用，取代溴化物成为第一个真正意义上的世界性抗癫痫药物并沿用至今； 1938年：苯妥英在美国上市，被誉为"癫痫患者的大赦年"，标志着第一代抗癫痫药物成熟（图2）。此后，第二代、第三代抗癫痫药物相继问世。近五年来，全球约有203个化合物处于临床前或临床I-III期研究阶段，彰显了制药行业对该领域持续高涨的研发热情。图2 抗癫痫药物发展史 03 第一代抗癫痫药物的偶然发现与演进逻辑第一代抗癫痫药物的发现充满传奇色彩，体现了从偶然到必然的科学发展规律。溴化物：19世纪20年代由法国化学家合成，但长期未被应用。1857年，Edward爵士在伦敦会议上报告52例病例，会议主席Locock（英国王室御用医生）分享其使用溴化钾治疗癔症性癫痫的经验。随后Radcliffe与Wilks等临床医生开展实践，Radcliffe率先发表系统性论文确立其疗效。然而，该药物因导致严重皮肤损害及精神症状（痴呆、躁狂、抑郁）而逐渐退出市场。苯巴比妥：德国拜耳公司创始人拜耳合成的苯二酰脲化合物，在庆祝酒会上因"芭芭拉舞步"与"脲"结合而得名巴比妥酸。1903年德国化学家发现其镇静催眠作用，1904年以Luminal为商品名上市。1912年，拜耳公司意外发现其抗癫痫功效。尽管存在显著镇静作用和认知功能影响，但因价格低廉，目前仍在全球经济落后地区使用。丙戊酸：德国化学家最初合成后仅作为惰性溶剂使用。法国里昂大学研究人员在使用其溶解中草药时发现所有溶液均显示抗癫痫活性，最终确认是溶剂本身（丙戊酸）起效。1967年上市后，丙戊酸成为全球处方量最大的抗癫痫药物，并在精神科领域扩展应用于双相情感障碍的治疗。从化学结构看，已上市抗癫痫药物多含苯环结构，仅丙戊酸作为脂肪酸类结构具有特殊性。 04 抗癫痫药物四大类作用机制解析抗癫痫药物通过调控突触传递网络发挥疗效，主要作用靶点分布于突触前膜、突触间隙及突触后膜。根据机制可分为四大类（图3）：第一类：电压门控性离子通道调节剂作用于钠、钾、钙离子通道，代表药物包括卡马西平、拉莫三嗪等；第二类：GABA介导的抑制增强剂通过增强γ-氨基丁酸（GABA）抑制功能发挥作用，代表药物为丙戊酸、苯二氮䓬类药物；第三类：谷氨酸受体介导的兴奋性突触抑制剂如吡仑帕奈；第四类：突触神经递质释放调节剂如左乙拉西坦、加巴喷丁等。这种多靶点、多机制的分类体系为临床合理用药提供了理论基础。图3.抗癫痫药物作用机制 05 抗癫痫药物研发体系：从ASP到ETSP的演进现代抗癫痫药物研发体系的建立归功于美国国立卫生研究院（NIH）癫痫领域卓越领导者Penry。1975年，NIH成立癫痫药物开发机构，启动抗癫痫药物筛查计划（ASP），2015年升级为癫痫治疗筛查计划（ETSP）。 ETSP聚焦三大关键研究方向： 1.耐药性癫痫测试模块：针对难治性癫痫模型开发新策略； 2.遗传性癫痫模块：以Dravet综合征（SCN1A基因突变）为代表的单基因癫痫； 3.慢性癫痫模型：识别可阻止癫痫发生发展的化合物。该计划建立了两个重要公共数据库： ·PANAChE：神经活性与抗癫痫小分子化合物评价数据库； ·可搜索的非保密性药效数据存储库，为后续研究提供开放共享平台。其中耐药性癫痫测试模块采用系统化的动物模型（如杏仁核红藻氨酸小鼠模型）和行为学观察，分鉴定阶段与个体化给药阶段，为新药筛选提供标准化流程。 06 当前抗癫痫药物研发的核心挑战与未满足需求尽管小分子化合物研发取得进展，但领域仍面临多重挑战： 1.耐药性机制不明：使用第三种药物无效后耐药机制复杂，需探索新策略； 2.个体异质性极高：癫痫患者个体差异显著，"如树叶般无一相同"； 3.致病机制复杂：多因素参与的病理网络，增加研发难度； 4.癫痫持续状态：导致神经元不可逆损伤的急症状态亟需针对性药物； 5.预防性治疗空白：如何在疾病早期干预、阻断其发生发展是未来关键方向。这些挑战构成了当前临床需求与研发重点的落差，也指明了创新突破口。 07 在研抗癫痫药物管线全景分析目前全球在研的抗癫痫药物超900种，处于临床前及临床阶段的约200余种。研发热潮得益于四大驱动力：遗传学与基因检测技术进步、孤儿药商业模式吸引力、胶质细胞等新机制发现、耐药性癫痫的迫切需求。在研药物按靶点与机制可分为十五大类： 1. GABA_A受体正变构调节剂（PAMs）：通过改变受体构象增强氯离子内流，使细胞膜超极化抑制兴奋。多家企业产品进入III期临床； 2. GABA_A受体逆激动剂：调控方向相反的创新机制； 3. GABA能转运体抑制剂：如卫材公司E2730进入I期临床； 4. 谷氨酸受体调节剂：包括正变构剂、NAMs和拮抗剂等多种亚型； 5. 谷氨酸转运体EAAT2正变构剂； 6. 五羟色胺神经递质调节剂：卫材公司产品针对Dravet综合征和发育性癫痫性脑病（DEEs）进入III期； 7. 钾通道激活剂：珠海丽珠与Xenon Pharmaceuticals合作开发的XEN1101已进入III期，较早期因视网膜毒性退市的品种具有更精准的亚单位选择性； 8. 钠通道调节剂：多个I/II期项目进行中； 9. 钙通道调节剂； 10. 抗炎与抗毒性机制药物； 11. 其他小分子化合物； 12. 多靶点综合机制药物； 13. 腺相关病毒（AAV）基因治疗：ETX101针对Dravet综合征的SCN1A基因突变，2024年已在英国启动临床试验；中国廖卫平教授团队亦开展同类研究； 14. 反义寡核苷酸药物：Stoke Therapeutics针对Dravet综合征的II期研究取得显著效果； 15. RNA疗法与新型细胞靶向治疗：聚焦小胶质细胞、星形胶质细胞等非神经元靶点，如鞘氨醇-1-磷酸受体调节剂、mTOR通路抑制剂（依维莫司）针对结节性硬化相关癫痫。从管线整体分析，大部分药物仍处于临床前阶段，仅少数进入III期，但进展迅速。遗传性癫痫尤其是Dravet综合征成为基因治疗突破的先锋阵地。 08 抗癫痫药物研发的成功经验与失败教训成功案例为行业指明方向：西诺氨酯（Cenobamate）：韩国SK公司研发，近期在国内获批。该药突破难治性癫痫天花板，将难治性癫痫比例从30%降至17%。秦兵教授团队在西诺氨酯国际多中心III期临床试验中，观察到海马硬化所致的难治性癫痫患者在多种药物及手术失败后，添加西诺氨酯实现无发作，随访两年仍无发作。 Cerliponase alfa：酶替代疗法治疗CLN2基因突变所致的神经元蜡样脂褐质沉积症（NCL）。该疾病导致患者关键酶活性降至正常8%，引发癫痫、痴呆、瘫痪。但年治疗费用高达70万美元，凸显罕见病治疗的可及性挑战，秦兵教授团队通过1Hz闪光刺激电生理标记物、基因检测和酶学诊断精准诊断了一家系三个小孩同患晚婴型NCL，系统梳理了酶替代疗法和基因治疗的国际最新进展。布立西坦（Brivaracetam）：相比左乙拉西坦具有更精准的突触囊泡蛋白靶点，疗效更优、副作用更小。秦兵教授团队在布立西坦国际多中心III期临床试验中发现，对位于中央叶功能区的药物难治性癫痫患者，布立西坦添加治疗可让每日多次发作的患者实现无发作，随访三年仍无发作。依维莫司（Everolimus）：mTOR通路抑制剂在结节性硬化相关癫痫靶向治疗疗效显著。失败案例同样提供深刻启示：帕西伏尼（Padsevonil）：UCB公司在左乙拉西坦基础上针对突触囊泡SV亚型优化，临床前与II期研究有效，但RCT试验失败，凸显机制复杂性。布雷沙诺酮（Brexanolone）：针对超难治癫痫持续状态（SRSE），I/II期有效性高，但RCT显示与安慰剂无差异，可能因剂量不足导致靶标结合率不够。布美他尼（Bumetanide）：钠钾通道抑制剂因无法选择性靶向中枢神经元NKCC1且脑内浓度不足而失败。这些案例表明，即便在明确的病理生理基础上，临床转化仍面临剂量、靶向性、生物利用度等多重不确定性。 09 未来抗癫痫药物研发的三大战略方向展望未来，研发战略聚焦于：方向一：老靶点的再开发 GABA受体作为经典靶点在2020年后持续焕发活力。由于GABA_A受体由五个亚基组成，各亚基均可成为精准干预位点，新一代药物通过亚型选择性实现副作用最小化与疗效最大化，形成GABA受体靶点的"复兴之路"。方向二：非神经元细胞靶点的探索传统药物聚焦神经元，近年发现小胶质细胞、星形胶质细胞及免疫细胞在癫痫发生中起关键作用。这些细胞上的新靶点（如鞘氨醇-1-磷酸受体、mTOR通路）为药物开发开辟全新维度，特别是针对结节性硬化等复杂疾病显示出协同价值。方向三：人工智能与机器学习赋能药物发现传统药物研发存在耗时长、成本高、失败率高的痛点。AI技术可在大规模数据筛选、建模分析中提前剔除低潜力化合物，显著节省时间与资金成本。近期机器学习已直接参与抗癫痫药物靶点设计与优化，为开发新药提供关键指导。写在最后秦兵教授的深入浅出的报告为我们展现了抗癫痫药物从19世纪溴化物的偶然发现，到21世纪基因治疗与AI驱动的精准医疗的抗癫痫全景图。核心价值挑战在于破解抗癫痫药物耐药性机制、实现个体化治疗、开发预防性干预策略。未来，基于明确基因分型的精准治疗（如Dravet综合征的基因疗法）、老靶点再开发、新作用机制的发现以及AI赋能的药物发现将成为突破现有疗效天花板的关键路径。 ✎ 秦兵教授简介秦兵教授是广东省杰出青年医学人才，暨南大学博士生导师，日本、法国和意大利多国访问学者，国际、国内多中心数十项抗癫痫药物RCT临床试验PI，曾荣获"中国好大夫"、"岭南名医"、“羊城好医生“、”全国十大医学人文专家”：全国十大医学新锐“等荣誉称号。在过去十余年间，他引进并翻译了大量国外经典医学名著，系统性撰写了600余篇癫痫病学科学史、人文系列文章，以巧妙的构思、引人入胜的故事、优美的文字和精美的插图向普罗大众传递有温度的专业医学知识，在癫痫疾病教育与科学传播方面做出了卓越的贡献。共建Biomedical创新生态圈！如何加入BiG会员？

2026-02-23

·PRNewswire

BioMarin Reports Fourth Quarter and Full-year 2025 Financial and Operating Results

Full-year 2025 Total Revenues Increased 13% Y/Y to $3.2 Billion, Led by 9% Revenue Growth for Enzyme Therapies and 26% Revenue Growth for VOXZOGO® Fourth Quarter 2025 Total Revenues Increased 17% Y/Y Led by 13% Revenue Growth for Enzyme Therapies and 31% Revenue Growth for VOXZOGO Announced Definitive Agreement to Acquire Amicus Therapeutics, including Galafold® for Fabry Disease and Pombiliti® + Opfolda® for Pompe Disease; Expected to Significantly Accelerate and Diversify Revenues BioMarin Provides 2026 Guidance Excluding any Post-Close Contribution from the Announced Acquisition of Amicus, Anticipated to Close in Q2'26 Conference Call and Webcast Scheduled Today at 4:30 p.m. ET SAN RAFAEL, Calif., Feb. 23, 2026 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced financial results for the fourth quarter and full year ended December 31, 2025. "In 2025, operational excellence led to strengthening financial results, including double-digit topline growth, strong profitability and increasing cash flow. We also advanced multiple medicines in our pipeline and closed the year by announcing the acquisition of Amicus," said Alexander Hardy, President and Chief Executive Officer of BioMarin. "The Amicus transaction, which is expected to close in the second quarter, represents a compelling opportunity to reach more patients around the world and further strengthen our revenue growth through the next decade." "We expect to build on this success in 2026, with another year of strong financial performance and momentum across the business. We look forward to adding Galafold and Pombiliti + Opfolda to our growing commercial enzyme therapies business, and to continued strong growth from VOXZOGO. Beyond our current commercial portfolio, we are excited by the progress we are seeing across our R&D pipeline and look forward to a multitude of pipeline catalysts throughout the year. These include three major data read-outs to support regulatory approvals, two age label expansions, plus the advancement of multiple clinical programs position us for significant portfolio progress. We are energized by what lies ahead this year and intend to deliver again on an ambitious set of priorities, demonstrating our dedication to innovation and sustained growth in ways that we believe will benefit patients, employees, and shareholders." 2025 Business Highlights Innovation Accelerated development of BMN 333, BioMarin's long-acting C-type natriuretic peptide (CNP), with Phase 1 PK data exceeding targeted free CNP exposure levels, reflecting its potential to become the new standard of care in achondroplasia. Advanced five new VOXZOGO indications within the CANOPY program, including a pivotal Phase 3 study in hypochondroplasia and Phase 2 studies in idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency. Reported positive data from the PALYNZIQ® Phase 3 PEGASUS study in 12- to 17-year-olds demonstrating statistically significant reductions in blood phenylalanine (Phe) compared to diet alone for adolescents with PKU. Progressed BMN 351 for Duchenne muscular dystrophy, with initial Phase 1/2 data demonstrating 5.0% mean absolute dystrophin expression (without double-correction for histologic adjustment for muscle content) at week 25 in the 9 mg/kg cohort. The 12 mg/kg dose cohort continues to enroll participants, with topline data readout from this cohort expected in 2H'26. Growth Strong patient demand across the portfolio fueled 13% Y/Y full-year 2025 total revenue growth. Enzyme Therapies full-year 2025 revenue advanced 9% Y/Y, supported by sustained high market penetration and patient adherence, led by robust 22% Y/Y growth from PALYNZIQ. VOXZOGO generated 26% Y/Y revenue growth for full-year 2025, driven by deeper market penetration and increasing demand for the treatment of achondroplasia across 55 commercial markets. Markets outside of the U.S. (OUS) drove approximately 73% of VOXZOGO revenue in full-year 2025, reflecting the therapy's strong uptake across global markets. Value Commitment Announced the acquisition of Amicus Therapeutics in December 2025, expected to close in Q2'26, subject to regulatory clearances, approval by the stockholders of Amicus and other customary closing conditions. The addition of high-growth products, Galafold for Fabry Disease and Pombiliti + Opfolda for Pompe Disease, is expected to accelerate BioMarin's revenue growth and increase profitability. Adolescent label expansion for Pombiliti + Opfolda is anticipated in 2H'26. Generated operating cash flows totaling $100 million in fourth quarter 2025 and $828 million for the full year. Total cash and investments totaled approximately $2 billion at year-end, and continued increasing operating cash flow is expected to support sustained investment in innovation and future growth. Strong performance in 2025 led to significant GAAP and Non-GAAP Diluted Earnings per Share expansion, excluding acquired in-process research and development (IPR&D) charges related to the acquisition of Inozyme, $1.10 per share, and an inventory write-off related to ROCTAVIAN®, totaling $0.46 per share after tax. The company secured financing of approximately $3.7 billion of non-convertible debt to support the Amicus acquisition with strong demand, achieving favorable pricing across the capital structure. Anticipated 2026 Program Updates VOXZOGO: Phase 3 hypochondroplasia data 1H'26; regulatory submissions 2H'26 U.S. supplemental new drug application (sNDA) for full approval of VOXZOGO in achondroplasia Q2'26 Advancing Phase 2 studies in idiopathic short stature, Noonan syndrome, Turner syndrome, SHOX deficiency BMN 333 (long-acting CNP): Initiate registration-enabling Phase 2/3 study in achondroplasia 1H'26 PALYNZIQ: U.S. PDUFA date for the adolescent label expansion February 28, 2026; EU approval 2026 BMN 401: Phase 3 topline data in 1 to 12 year-old population with ENPP1 deficiency 1H'26; global regulatory submissions 2H'26; potential first‑in‑disease launch 2027 BMN 351 Phase 1/2 data presentation for 6 mg/kg and 9 mg/kg cohorts at Muscular Dystrophy Association (MDA) Clinical & Scientific Congress (March 8–11, 2026) ROCTAVIAN Following the company's October announcement to explore options to divest ROCTAVIAN, BioMarin undertook a comprehensive effort to identify a potential buyer. Despite these efforts, BioMarin was unable to identify a qualified buyer and has made the decision to voluntarily withdraw ROCTAVIAN from the market. Fourth Quarter 2025 Financial Highlights Total Revenues for the fourth quarter of 2025 were $875 million, an increase of 17% compared to the same period in 2024, driven by 31% year-over-year VOXZOGO revenue growth from new patients initiating therapy across all regions and the timing of large government orders, primarily in Latin America. In the quarter, revenues from BioMarin's Enzyme Therapies (ALDURAZYME®, BRINEURA®, NAGLAZYME®, PALYNZIQ and VIMIZIM®) also increased by 13% compared to the fourth quarter of 2024, driven by a combination of increased patient demand in all regions and the timing of large government orders. GAAP Net Loss was $47 million for the fourth quarter of 2025 compared to GAAP Net Income of $125 million for the same period in 2024. The increase in GAAP Net Loss was primarily due to the company's strategic decision to voluntarily withdraw ROCTAVIAN from the market resulting in charges of approximately $240 million during the quarter. These charges were mainly comprised of $119 million of an inventory write-off that was included in Cost of Sales and $118 million of long-lived asset impairments included in Selling, General and Administrative expense. The increase in GAAP Net Loss was partially offset by improved revenue growth as mentioned above and lower provision for income taxes. Non-GAAP Income for the fourth quarter of 2025 decreased to $89 million compared to $180 million for the same period in 2024. The decrease in Non-GAAP Income was primarily due to the ROCTAVIAN inventory write- off included in Cost of Sales. The decrease in Non-GAAP Income was partially offset by improved revenue growth as mentioned above. Forward-Looking Non-GAAP Financial Information BioMarin does not provide guidance for GAAP reported financial measures (other than revenue) or a reconciliation of forward-looking Non-GAAP financial measures to the most directly comparable GAAP reported financial measures because the company is unable to predict with reasonable certainty the financial impact of changes resulting from its strategic portfolio and business operating model reviews; potential future asset impairments; gains and losses on investments; and other unusual gains and losses without unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP reported results for the guidance period. As such, any reconciliations provided would imply a degree of precision that could be confusing or misleading to investors. 2026 Full-Year Financial Guidance (in millions, except EPS amounts) 2026 guidance excludes any post-close contribution from the announced acquisition of Amicus Therapeutics, anticipated to close in Q2'26 Total Revenues guidance reflects expectation of continued strong patient demand across Enzyme Therapies and VOXZOGO in 2026 Other Revenue guidance reflects KUVAN, royalty revenue (including conclusion of U.S. Firdapse royalty term in January 2026), and the company's strategic decision to voluntarily withdraw ROCTAVIAN from the market Non-GAAP Diluted EPS guidance includes approximately $0.25 of pre-close operating and interest expenses associated with the Amicus transaction In 2026, excluding the impact of the Amicus transaction, Non-GAAP Operating Margin is expected to be approximately 40% for the full year BioMarin will host a conference call and webcast to discuss fourth quarter 2025 financial results today, Monday, February 23, 2026, at 4:30 p.m. ET. This event can be accessed through this link or on the investor section of the BioMarin website at . About BioMarin BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with multiple commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients. To learn more, please visit . Forward-Looking Statements This press release and the associated conference call and webcast contain forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: future financial performance, including the expectations of Total Revenues, Non-GAAP Operating Margin percentage, and Non-GAAP Diluted EPS for the full-year 2026 and future periods, and the underlying drivers of those results, such as the expected demand and continued growth of BioMarin's Enzyme Therapies portfolio, the expected growth from VOXZOGO, and the expected impact of Other Revenues; the anticipated closing and benefits of BioMarin's proposed acquisition of Amicus Therapeutics, Inc.; BioMarin's plans for investment in innovation and future growth; the timing of orders for commercial products; plans and expectations regarding the development, commercialization and commercial prospects of BioMarin's product candidates and commercial products, including the prospects and timing of actions relating to clinical studies and trials and product approvals, such as study initiations, study advancements, data readouts, submissions, filings, approvals, and label expansions; the expected benefits and availability of BioMarin's commercial products and product candidates; and potential growth opportunities and trends, including the assumptions and expectations regarding total addressable patient population (TAPP) with respect to the conditions targeted by BioMarin's product candidates and commercial products. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: BioMarin's success in the commercialization of its commercial products; BioMarin's ability to consummate and realize the anticipated benefits of any acquisitions; impacts of macroeconomic and other external factors on BioMarin's operations, regulatory uncertainty, the impact of new or increased tariffs, other trade protection measures, and escalating trade tensions; results and timing of current and planned preclinical studies and clinical trials and the release of data from those trials; BioMarin's ability to successfully manufacture its commercial products and product candidates; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities concerning each of the described products and product candidates; the market for each of these products; BioMarin's ability to meet product demand; actual sales of BioMarin's commercial products; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, as such factors may be updated by any subsequent reports. Investors are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, VOXZOGO®, VIMIZIM®, NAGLAZYME®, PALYNZIQ®, BRINEURA®, KUVAN® and ROCTAVIAN® are registered trademarks of BioMarin Pharmaceutical Inc., or its affiliates. ALDURAZYME® is a registered trademark of BioMarin/Genzyme LLC. All other brand names and service marks, trademarks and other trade names appearing in this release are the property of their respective owners. Non-GAAP Information The results presented in this press release include both GAAP information and Non-GAAP information. Non-GAAP Income is defined by the company as GAAP Net Income (Loss) excluding amortization of intangible assets, stock-based compensation expense and, in certain periods, certain other specified items, as detailed below when applicable. The company also includes a Non-GAAP adjustment for the estimated tax impact of the reconciling items. Non-GAAP R&D expenses and Non-GAAP SG&A expenses are defined by the company as GAAP R&D expenses and GAAP SG&A expenses, respectively, excluding stock-based compensation expense and, in certain periods, certain other specified items, as detailed below when applicable. Non-GAAP Operating Margin percentage is defined by the company as GAAP Income (Loss) from Operations, excluding amortization of intangible assets, stock-based compensation expense and, in certain periods, certain other specified items, divided by GAAP Total Revenues. Non-GAAP Diluted EPS is defined by the company as Non-GAAP Income divided by Non-GAAP Weighted-Average Diluted Shares Outstanding. Non-GAAP Weighted-Average Diluted Shares Outstanding is defined by the company as GAAP Weighted-Average Diluted Shares Outstanding, adjusted to include any common shares issuable under the company's equity plans or convertible debt in periods when they are dilutive under Non-GAAP. BioMarin regularly uses both GAAP and Non-GAAP results and expectations internally to assess its financial operating performance and evaluate key business decisions related to its principal business activities: the discovery, development, manufacture, marketing and sale of innovative biologic therapies. BioMarin also uses Non-GAAP Income internally to understand, manage and evaluate its business and to make operating decisions, and compensation of executives is based in part on this measure. Because these Non-GAAP metrics are important internal measurements for BioMarin, the company believes that providing this information in conjunction with BioMarin's GAAP information enhances investors' and analysts' ability to meaningfully compare the company's results from period to period and to its forward-looking guidance, and to identify operating trends in the company's principal business. Non-GAAP financial measures are not meant to be considered in isolation or as a substitute for, or superior to comparable GAAP measures and should be read in conjunction with the consolidated financial information prepared in accordance with GAAP. Investors should note that the Non-GAAP information is not prepared under any comprehensive set of accounting rules or principles and does not reflect all of the amounts associated with the company's results of operations as determined in accordance with GAAP. Investors should also note that these Non-GAAP financial measures have no standardized meaning prescribed by GAAP and, therefore, have limits in their usefulness to investors. In addition, from time to time in the future there may be other items that the company may exclude for purposes of its Non-GAAP financial measures; likewise, the company may in the future cease to exclude items that it has historically excluded for purposes of its Non-GAAP financial measures. Because of the non-standardized definitions, the Non-GAAP financial measure as used by BioMarin in this press release and the accompanying tables may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. The following tables present the reconciliation of GAAP reported to Non-GAAP adjusted financial information: SOURCE BioMarin Pharmaceutical Inc. 21% more press release views with Request a Demo

临床3期临床结果并购财报临床1期

100 项与阿尔法脂肪酶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10813	-	A16AB17	DB13173

研发状态

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适应症	国家/地区	公司	日期
神经元蜡样质脂褐质沉积症	欧盟	BioMarin International Ltd.	2017-05-30
神经元蜡样质脂褐质沉积症	冰岛	BioMarin International Ltd.	2017-05-30
神经元蜡样质脂褐质沉积症	列支敦士登	BioMarin International Ltd.	2017-05-30
神经元蜡样质脂褐质沉积症	挪威	BioMarin International Ltd.	2017-05-30
神经元蜡样脂褐质沉积症2	美国	BioMarin Pharmaceutical, Inc.	2017-04-27

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02678689 (IEC2023)	临床2期	神经元蜡样脂褐质沉积症2	14	Cerliponase alfa	鏇餘簾窪夢夢積糧製膚(淵顧築網鑰憲選鏇願構) = All subjects experienced ≥1 AE; the most common drug-related AEs were pyrexia and hypersensitivity. Twelve subjects experienced ≥1 serious AE; there were no deaths or discontinuations due to AEs. 膚憲選繭顧膚襯觸糧網 (夢製淵鬱構鹹構夢鏇築 ) 更多	积极	2023-09-04
NCT02678689 (IEC2023)	临床2期	神经元蜡样脂褐质沉积症2	14	Cerliponase alfa (Historical controls)		积极	2023-09-04
NCT02485899 (extension study, IEC2019)	临床1/2期	神经元蜡样脂褐质沉积症2 TPP1 deficiency	24	Cerliponase alfa 300 mg	憲繭齋範鬱簾獵壓鑰構(範鹽艱膚鑰鬱繭餘艱衊) = Common AEs included pyrexia, vomiting, and convulsion 鹹齋鹹鏇製簾簾獵構範 (壓壓襯廠壓齋構鹹衊鹹 ) 更多	积极	2019-06-24
NCT01907087 \| NCT02485899 (CNS2018)	临床1/2期	神经元蜡样脂褐质沉积症2	24	Cerliponase Alfa 300 mg	築遞鏇願鑰顧觸鹹糧繭(膚蓋範糧鏇鑰顧醖艱鑰) = Common AEs included convulsion 觸廠醖鏇鹹窪膚構範衊 (顧餘艱範壓衊淵鹽築壓 ) 更多	积极	2018-10-05
NCT01907087 (###DELETE, CTgov)	临床1/2期	神经元蜡样脂褐质沉积症2	24	BMN	齋壓繭廠簾鹹築築鏇鏇(鬱鑰簾醖艱夢廠簾範鏇) = 鏇鏇繭顧壓艱觸遞鹹鬱築繭蓋壓衊獵壓膚壓簾 (積艱構廠襯範築窪鏇願, 1.2) 更多	-	2018-06-11
NCT01907087 \| NCT02485899 (IEC2017)	临床1/2期	神经元蜡样质脂褐质沉积症 TPP1 deficiency	24	Cerliponase alfa 300 mg	簾鑰壓艱壓觸鑰構艱壓(襯遞鬱齋鬱築鏇齋鬱築) = All had AEs; most were Grade 1 - 2. Common AEs included pyrexia, hypersensitivity and convulsion. Nineteen (79%) subjects had at least one serious AE, which were mostly consistent with neurodegenerative disease in a pediatric population 範憲鹽餘鏇網鬱鹽願淵 (選積醖鑰觸網繭鏇製醖 ) 更多	积极	2017-09-05
NCT01907087 \| NCT02485899 (IEC2017)	临床1/2期	神经元蜡样质脂褐质沉积症 TPP1 deficiency	24	Placebo		积极	2017-09-05
CNS2016	临床1/2期	神经元蜡样脂褐质沉积症2 TPP1 enzyme deficiency	24	Cerliponase alfa 300mg	淵餘觸鑰艱鏇觸窪壓糧(願艱觸繭繭醖憲獵觸選) = 17% 衊積齋獵糧觸願願憲艱 (夢夢觸廠窪艱齋網鹽築 ) 更多	-	2016-10-14