摘要：美国FDA批准Ultragenyx的基因疗法Fayuvi（rebisufligene etisparvovec-hopf）上市，用于儿科患者黏多糖贮积症IIIA型（MPS IIIA、Sanfilippo综合征A型）治疗。这是该罕见神经系统退行性疾病的首个获批疗法。
The U.S. Food and Drug Administration today approved Fayuvi (rebisufligene etisparvovec-hopf), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A., MPS IIIA is a rare inherited disease that progressively damages the brain and nervous system, causing children to lose cognitive, language and other developmental abilities over time. Until today, treatment was limited to managing symptoms; there was no FDA-approved therapy designed to change the underlying course of the disease.
“The Trump Administration is committed to bringing safe and effective treatments to patients with the most urgent and unmet needs. The approval of Fayuvi marks a historic moment for children and families living with MPS IIIA, which is a disease that has, until now, offered no approved treatment to alter its devastating course,” said Acting FDA Commissioner Kyle Diamantas, J.D. “Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A, and this milestone reflects the FDA’s commitment to action.”
Fayuvi is a one-time, intravenous (given directly into a vein) gene therapy that uses a modified, non-infectious virus called an adeno-associated virus serotype 9 (AAV9) to deliver a working copy of the SGSH gene into the patient’s cells. This enables the body’s cells to produce sulfamidase — the enzyme that is missing or deficient in MPS IIIA — allowing heparan sulfate to be properly broken down in lysosomes and reducing its harmful buildup throughout the body and brain.
“For families living with Sanfilippo syndrome type A, the trajectory of this disease is heartbreaking — children who develop normally in their earliest years facing a relentless regression with no approved treatment to slow it. Parents and clinicians have been waiting far too long for an option,” said Karim Mikhail, B. Pharm., M.S., Director of the Center for Biologics Evaluation and Research. “Today’s approval of Fayuvi is a meaningful step forward — not only for these children and their families, but for the promise of gene therapy to address rare and devastating diseases where the need for safe and effective treatment is the most urgent.”
The safety and effectiveness of Fayuvi was evaluated in an open-label, single-arm, multicenter clinical study in pediatric patients with MPS IIIA. The study measured mean changes in cognitive scores in patients between the ages of 2 and 5 years. Fayuvi-treated patients maintained or improved cognitive function compared to an untreated historical control cohort — a meaningful divergence from the expected natural disease course of plateau and decline during this critical developmental window.
“Achieving meaningful neurodevelopmental benefit through a single intravenous administration represents a significant scientific milestone — demonstrating that systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutically relevant levels in pediatric patients. This approval underscore OTP’s and FDA’s commitment to applying rigorous evidentiary standards as the field of gene therapy continues to advance,” said Megha Kaushal, M.D., M.Sc., Acting Deputy Director of the Office of Therapeutic Products.
The safety of Fayuvi was evaluated in pediatric patients who received a single intravenous infusion across clinical studies. The most commonly adverse reactions reported in more than 5% of patients were increases in liver enzymes (AST), nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts and increased amylase. Important safety warnings include the risk of thrombotic microangiopathy (TMA). As with other AAV-based gene therapies, there is a potential long-term risk that the inserted genetic material could integrate into the genome and potentially lead to tumor development.
Fayuvi is administered in a healthcare setting equipped to manage infusion reactions. All patients receive corticosteroid treatment beginning one day before the infusion and continuing for a minimum of eight weeks afterward.
Fayuvi was granted Orphan Drug and Fast Track, and Breakthrough Therapydesignations. The FDA granted Fayuvi approval to Ultragenyx Pharmaceutical, Inc.
美国食品药品监督管理局批准
Fayuvi（rebisufligene etisparvovec‑hopf）上市，用于治疗黏多糖贮积症 IIIA 型（MPS IIIA，又称山菲利普综合征 A 型）儿科患者，这是该疾病的首款治疗药物。黏多糖贮积症 IIIA 型是一种罕见遗传病，会进行性损伤大脑与神经系统，患儿会随时间逐步丧失认知、语言及其他发育能力。在此之前，临床仅能开展对症处理，尚无 FDA 批准的疗法可改变疾病的根本病程。
FDA 代理局长凯尔・迪亚曼塔斯法学博士（Kyle Diamantas, J.D.）表示：“特朗普政府致力于为存在最迫切未满足医疗需求的患者带去安全有效的治疗手段。Fayuvi 的获批，对于罹患 MPS IIIA 的患儿及其家庭而言具有里程碑意义。在此之前，尚无获批药物能够扭转该疾病毁灭性的进展。基因疗法为山菲利普综合征 A 型这类罕见病带来巨大希望，本次获批也彰显了 FDA 积极行动的决心。”
Fayuvi 为一次性静脉输注基因疗法，采用经过改造、无感染能力的 9 型腺相关病毒（AAV9）载体，将正常功能的 SGSH 基因拷贝递送至患者细胞内。促使人体细胞合成磺酰胺酶 —— 即 MPS IIIA 患者体内缺失或不足的酶，让硫酸乙酰肝素可在溶酶体内正常分解，减少该物质在全身及大脑中的有害蓄积。
美国食品药品监督管理局生物制品评价和研究中心主任卡里姆・米哈伊尔药学学士、理学硕士（Karim Mikhail, B. Pharm., M.S.）称：“对于山菲利普综合征 A 型患者家庭，该病的病程令人心碎：患儿幼年发育正常，之后却出现不可逆的功能倒退，且过去没有获批药物能够延缓这一过程。患儿父母与临床医生等待有效治疗选择已经太久。Fayuvi 今日获批意义重大，不仅惠及这些患儿及其家庭，也为基因疗法攻克其他需求迫切、预后凶险的罕见病带来新希望。”
Fayuvi 的安全性与有效性在一项开放标签、单臂、多中心临床试验中开展评价，受试者为 MPS IIIA 儿科患者。研究主要观察 2‑5 岁受试者认知评分的平均变化。与未接受治疗的历史对照队列相比，经 Fayuvi 治疗的患儿认知功能得以维持甚至获得改善；在这一关键发育阶段，该结果与疾病预期的平台期后逐步衰退的自然病程形成显著差异。
治疗产品办公室代理副主任梅加・考沙尔医学博士、理学硕士（Megha Kaushal, M.D., M.Sc.）指出：“仅通过单次静脉给药即可实现具有临床意义的神经发育获益，是一项重大科学突破，证明全身给药的 AAV9 基因递送系统能够以有效治疗浓度抵达儿科患者的中枢神经系统。本次获批也体现罕见病产品办公室（OTP）以及 FDA，在基因疗法快速发展过程中，始终坚持严谨证据标准。”
多项临床试验对单次静脉输注 Fayuvi 的儿科受试者开展安全性评估。发生率＞5% 的最常见不良反应包括：天门冬氨酸氨基转移酶（AST）升高、恶心呕吐、发热、食欲下降、白细胞计数降低、血小板计数下降以及淀粉酶升高。重要安全警示包含血栓性微血管病（TMA）风险。与其他 AAV 载体类基因疗法相同，插入的遗传物质存在整合至基因组的远期潜在风险，理论上有可能诱发肿瘤。
Fayuvi 必须在具备输注反应处置能力的医疗机构给药。所有受试者需在输注前一日开始使用糖皮质激素，给药后继续用药至少 8 周。
Fayuvi 获得 FDA 授予的孤儿药资格、快速通道资格以及突破性疗法认定。FDA 将该药品上市许可授予 Ultragenyx 制药公司。