UCB在AES上展示了GEMZ III期研究的积极结果，显示芬氟拉明显著降低了CDKL5缺陷障碍患者的可计数运动发作频率-动脉网

UCB presents positive results from GEMZ phase 3 study at AES showing fenfluramine significantly reduces countable motor seizure frequency in CDKL5 Deficiency Disorder

优时比等信源发布 2025-12-08 14:00

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可切换为仅中文

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Brussels, Belgium December 8th 2025 – 07:00 CET

比利时布鲁塞尔，2025年12月8日 – 07:00 欧洲中部时间

– UCB, a global biopharmaceutical company, today presented positive efficacy and safety results from the GEMZ phase 3 study investigating adjunctive fenfluramine in children and adults with CDKL5 Deficiency Disorder (CDD) at the American Epilepsy Society (AES) meeting, Atlanta, USA, December 5-9, 2025..

优时比（UCB），一家全球生物制药公司，于2025年12月5日至9日在美国亚特兰大举行的美国癫痫学会（AES）会议上公布了GEMZ III期研究的积极有效性和安全性结果，该研究探讨了辅助使用芬氟拉明在CDKL5缺陷症（CDD）儿童和成人患者中的效果。

The trial met its primary endpoint and key secondary endpoints, demonstrating a statistically significant reduction in countable motor seizure frequency (CMSF) and a clinically meaningful improvement on the Clinical Global Impression-Improvement (CGI-I) scale, compared with placebo.

该试验达到了主要终点和关键次要终点，与安慰剂相比，在可计数运动性癫痫发作频率（CMSF）上显示出统计学上的显著降低，并在临床总体印象改善（CGI-I）量表上表现出有临床意义的改善。

“UCB is proud to share these important results with the medical community at AES, especially given the significant unmet need in CDD. Families affected by this ultra-rare condition face immense daily challenges with frequent, treatment-resistant seizures that are profoundly disruptive to daily life.

“UCB很自豪能够在AES上与医学界分享这些重要的成果，尤其是在CDD领域存在显著未满足需求的情况下。受到这种超罕见疾病影响的家庭面临着巨大的日常挑战，频繁出现的、对治疗有抵抗性的癫痫发作极大地扰乱了日常生活。"

These trial results emphasize the impact that seizure control can have on the lives of patients and their families, and we look forward to working with health authorities to make this treatment available as soon as possible”, .

这些试验结果强调了癫痫控制对患者及其家人的生活影响，我们期待与卫生当局合作，尽快使这种治疗方案得以应用。

said Fiona du Monceau, Executive Vice President, Patient Evidence, UCB.

UCB患者证据执行副总裁菲奥娜·杜·蒙索说。

The GEMZ Phase 3 study is a randomized, double-blind, placebo-controlled, fixed-dose, multi-center study examining the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine treatment in 86 children and adults aged 1 – 35 years, with a CDD diagnosis and uncontrolled seizures.

GEMZ 第三阶段研究是一项随机、双盲、安慰剂对照、固定剂量、多中心研究，旨在评估辅助芬氟拉明治疗在86名1至35岁患有CDD诊断且癫痫发作未受控制的儿童和成人中的疗效、安全性和药代动力学。

Phase 3 study results

第三阶段研究结果

Patients treated with fenfluramine (n=42) (0.7mg/kg/day, maximum 26 mg/day) experienced a median reduction of 47.6% in CMSF from baseline, compared with a 2.8% for placebo (n=44) (p<0.001).1 This translated into an estimated median reduction of 52.7% (95% CI: −70.0 to −36.7) between treatment groups during a 14-week titration and maintenance period..

接受芬氟拉明治疗的患者（n=42）（0.7毫克/公斤/天，最大剂量26毫克/天）从基线开始，CMSF中位数减少了47.6%，而安慰剂组（n=44）仅减少2.8%（p<0.001）。在14周的滴定和维持期内，这相当于治疗组之间估计的中位数减少52.7%（95%置信区间：−70.0至−36.7）。

After 14 weeks, 45.2% (n=19) of fenfluramine-treated patients achieved at least 50% reduction in CMSF, compared with only 4.5% (n=2) of patients who received placebo (p<0.001).

在14周后，45.2%（n=19）的服用芬氟拉明的患者CMSF至少减少了50%，而仅接受安慰剂的患者中只有4.5%（n=2）达到同样效果（p<0.001）。

Most fenfluramine-treated patients experienced an increase in countable motor seizure-free days, with a median of >6 additional seizure free days a month from baseline compared with placebo

大多数服用芬氟拉明的患者经历了可计数的运动性癫痫无发作天数的增加，与安慰剂相比，每月从基线起中位数增加了超过6天的无发作天数。

Investigators rated 38.1% (n=16) of patients on fenfluramine as “much improved” or “very much improved” on the Clinical Global Impression–Improvement scale (CGI-I), compared with 6.8% (n=3) of those on placebo (p<0.001).

调查人员使用临床全局印象改善量表（CGI-I）评定38.1%（n=16）的服用芬氟拉明的患者为“显著改善”或“非常显著改善”，而安慰剂组仅为6.8%（n=3）（p<0.001）。

According to caregiver’s report of improvement, a CGI-I rating of ‘much improved’ or ‘very much improved’ was provided by 53.7% (n=22) vs just 2.3% (n=1) in the placebo group (p<0.001).

根据照顾者对改善情况的报告，53.7%（n=22）的患者被评为“显著改善”或“非常显著改善”，而安慰剂组仅为2.3%（n=1）（p<0.001）。

Fenfluramine was generally well tolerated in the trial, with no new safety signals identified and no cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) occurring.

在试验中，芬氟拉明通常耐受性良好，未发现新的安全信号，且未出现心脏瓣膜病（VHD）或肺动脉高压（PAH）的病例。

Treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of fenfluramine in Dravet syndrome and Lennox-Gastaut syndrome, with 14.3% (n=6) of patients who received fenfluramine experiencing serious TEAEs* compared to 6.7% (n=3) of patients who received placebo.

治疗中出现的不良事件 (TEAEs) 与芬氟拉明在Dravet综合征和Lennox-Gastaut综合征中的已知安全性特征一致，接受芬氟拉明的患者中有14.3%（n=6）经历了严重的TEAEs*，而接受安慰剂的患者中这一比例为6.7%（n=3）。

UCB is currently conducting an open-label, flexible-dose, long-term 54-week extension (52-week OLE treatment period + 2-week taper) phase of the study to characterize the long-term safety profile and tolerability of fenfluramine in children and adult individuals with CDD.

UCB目前正在进行一项开放标签、灵活剂量、为期54周的长期延长研究阶段（52周OLE治疗期+2周减量期），以评估芬氟拉明在患有CDD的儿童和成人中的长期安全性和耐受性。

CDD is an ultra-rare, DEE characterized by multiple types of drug-resistant seizures, plus severe global neurodevelopmental delays resulting in intellectual, motor, cortical visual, gastrointestinal and sleep impairments as major features. It is caused by pathogenic variants in the Cyclin Dependent Kinase-like 5 (CDKL5) gene located on the X chromosome and affects four times more females than males.

CDD是一种超罕见的DEE，其特征是多种类型的耐药性癫痫发作，以及严重的全面神经发育迟缓，导致智力、运动、皮层视觉、胃肠道和睡眠障碍为主要特征。它是由位于X染色体上的细胞周期蛋白依赖性激酶样5（CDKL5）基因的致病变异引起的，影响的女性比男性多四倍。

It is estimated that CDD affects approximately 1 in 40,000 to 60,000 live births, with a median age of onset of six weeks..

据估计，CDD影响大约每40,000到60,000名活产婴儿中的1名，发病的中位年龄为六周。

3,4,5,6,7

In the European Union (EU), fenfluramine is approved for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older.

在欧盟 (EU)，芬氟拉明被批准用于治疗与 Dravet 综合征和 Lennox-Gastaut 综合征相关的癫痫发作，作为 2 岁及以上患者其他抗癫痫药物的辅助疗法。

In the United States, fenfluramine oral solution is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older.

在美国，芬氟拉明口服溶液适用于治疗2岁及以上患者与Dravet综合征和Lennox-Gastaut综合征相关的癫痫发作。

In Japan, fenfluramine is approved for treating seizures associated with Dravet syndrome and Lennox-Gastaut syndrome (LGS) as an add-on therapy to other anti-epileptic medicines for patients 2 years and older.

在日本，芬氟拉明被批准用于治疗与Dravet综合征和Lennox-Gastaut综合征（LGS）相关的癫痫发作，作为2岁及以上患者其他抗癫痫药物的辅助疗法。

It is not approved for use in CDD by any regulatory authority worldwide.

世界上任何监管机构均未批准其用于CDD。

*Serious TEAEs included urinary tract infection (n=2), metapneumovirus infection (n=1), RSV pneumonia (n=1), decreased appetite (n=1), and dyskinesia (n=1) in patients on FFA, and gastroenteritis and pneumoperitoneum in the 2 patients on PBO

FFA组患者中的严重TEAE包括尿路感染（n=2）、偏肺病毒感染（n=1）、呼吸道合胞病毒肺炎（n=1）、食欲减退（n=1）和运动障碍（n=1），而PBO组的2名患者中则出现胃肠炎和气腹。

For further information, contact UCB:

如需更多信息，请联系UCB：

Global Communications

全球通讯

Anna Clark

安娜·克拉克

T: +44.73.8.668.67.79

电话：+44.73.8.668.67.79

Anna.clark@ucb.comm

安娜.克拉克@ucb.comm

Corporate Communications, Media Relations

企业传播、媒体关系

Laurent Schots

劳伦特·肖茨

T +32.2.559.92.64

电话：+32.2.559.92.64

Laurent.schots@ucb.com

劳伦特·肖茨@ucb.com

Investor Relations

投资者关系

Antje Witte

安特耶·维特

T +32.2.559.94.14

电话：+32.2.559.94.14

antje.witte@ucb.com

Sahar Yazdian

萨哈尔·亚兹迪安

T +32.2.559.91.37

电话：+32.2.559.91.37

sahar.yazdian@ucb.com

About UCB

关于UCB

UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9,000 people in approximately 40 countries, the company generated revenue of € 6.15 billion in 2024.

优时比公司（UCB），位于比利时布鲁塞尔（www.ucb.com），是一家全球生物制药公司，专注于发现和开发创新药物及解决方案，以改变免疫系统或中枢神经系统严重疾病患者的生活。该公司在约40个国家拥有大约9,000名员工，并在2024年创造了61.5亿欧元的收入。

UCB is listed on Euronext Brussels (symbol: UCB)..

UCB在布鲁塞尔泛欧交易所上市（代码：UCB）。

UCB Forward Looking Statement

加州大学伯克利分校前瞻性声明

This document contains forward-looking statements, including, without limitation, statements containing the words “potential”, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will”, “continue” and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management.

本文件包含前瞻性陈述，包括但不限于包含“潜在”、“相信”、“预期”、“预计”、“打算”、“计划”、“寻求”、“估计”、“可能”、“将”、“继续”等词语及类似表达的陈述。这些前瞻性陈述基于管理层当前的计划、估计和信念。

All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results.

所有声明，除历史事实声明外，均可能被视为前瞻性声明，包括收入、营业利润率、资本支出、现金、其他财务信息、预期法律、仲裁、政治、监管或临床结果或实践以及其他此类估计和结果。

By their nature, such forward-looking statements are not guaranteeing future performance and are subject to known and unknown risks, uncertainties, and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements contained in this document. .

由于其性质，此类前瞻性声明并不能保证未来的表现，并且受到已知和未知风险、不确定性及假设的影响，这些因素可能导致UCB的实际结果、财务状况、表现或成就，或者行业结果，与本文件中包含的此类前瞻性声明所明示或暗示的任何未来结果、表现或成就存在重大差异。

Important factors that could result in such differences include but are not limited to: global spread and impacts of wars, pandemics and terrorism, the general geopolitical environment, climate change, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues, supply chain disruption and business continuity risks; potential or actual data security and data privacy breaches, or disruptions of UCB’s information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars or disruptive technologies/business models, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in laws and/or rules pertaining to tax and duties or the administration of such laws and/or rules, and hiring, retention and compliance of employees.

可能导致此类差异的重要因素包括但不限于：战争、疫情和恐怖主义的全球蔓延及影响、总体地缘政治环境、气候变化、总体经济、商业和竞争状况的变化、无法获得必要的监管批准或在可接受的条件或预期时间内获得批准、与研发相关的成本、UCB在研产品或开发中产品的前景变化、未来司法裁决或政府调查的影响、安全性、质量、数据完整性或生产问题、供应链中断和业务连续性风险；潜在或实际的数据安全和隐私泄露，或UCB信息技术系统的中断、产品责任索赔、对产品或候选产品的专利保护挑战、来自其他产品（包括生物类似药）或颠覆性技术/商业模式的竞争、法律法规的变化、汇率波动、与税收和关税相关的法律和/或规则及其管理的变化或不确定性，以及员工的招聘、留任和合规问题。

There is no guarantee that new product candidates will be discovered or identified in the pipeline, or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans.

无法保证在研发管线中会发现或识别出新的产品候选者，也无法保证现有产品的新的适应症能够被开发和批准。从概念到商业产品的推进过程充满不确定性；临床前结果并不能保证产品候选者在人体中的安全性和有效性。

So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has.

到目前为止，计算机模型、细胞培养系统或动物模型无法再现人体的复杂性。完成临床试验和获得产品上市监管批准的时间长度已经。

Given these uncertainties, the public is cautioned not to place any undue reliance on such forward-looking statements. These forward-looking statements are made only as of the date of this document, and do not reflect any potential impacts from the evolving event or risk as mentioned above as well as any other adversity, unless indicated otherwise.

鉴于这些不确定性，公众被提醒不要对这些前瞻性声明给予任何过度依赖。这些前瞻性声明仅自本文档发布之日起作出，并不反映上述不断演变的事件或风险以及任何其他不利因素的潜在影响，除非另有说明。

The company continues to follow the development diligently to assess the financial significance of these events, as the case may be, to UCB..

公司继续勤勉地跟进事态发展，以评估这些事件对UCB的财务影响（如有）。

UCB expressly disclaims any obligation to update any forward-looking statements in this document, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations..

UCB明确表示，除非适用法律法规要求，否则不对更新本文件中的任何前瞻性声明承担任何义务，无论该等声明是为了确认实际结果，还是为了报告或反映与之相关的前瞻性声明的任何变更，或是任何作为该等声明基础的事件、条件或情况的变更。

Important Safety Information about FINTEPLA

关于FINTEPLA的重要安全信息

▼ (fenfluramine) in the EU

▼ （芬氟拉明）在欧盟

Indications

适应症

: Treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older.

用于治疗与Dravet综合征和Lennox-Gastaut综合征相关的癫痫发作，作为2岁及以上患者其他抗癫痫药物的辅助疗法。

Dosage and Administration

用法与用量

: Please refer to SmPC for full information. Should be initiated and supervised by physicians with experience in the treatment of epilepsy. Fintepla is prescribed and dispensed according to the Fintepla controlled access programme. Dravet syndrome: Patients who are

：有关完整信息，请参阅SmPC。应由有癫痫治疗经验的医生启动和监督。Fintepla根据Fintepla管控获取计划进行处方和分发。Dravet综合征：患者

not

不是

taking stiripentol: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, if tolerated, can increase dose to 0.2 mg/kg twice daily (0.4 mg/kg/day). After an additional 7 days, if tolerated and further seizure reduction required, can increase dose to a maximum of 0.35 mg/kg twice daily (0.7 mg/kg/day), which is the recommended maintenance dose.

服用司替戊醇：起始剂量为每天两次0.1毫克/千克（每天0.2毫克/千克）。7天后，如果耐受良好，可将剂量增加至每天两次0.2毫克/千克（每天0.4毫克/千克）。再过7天后，如果耐受良好且需要进一步减少癫痫发作，可将剂量增加至最大剂量，即每天两次0.35毫克/千克（每天0.7毫克/千克），这是推荐的维持剂量。

Patients requiring more rapid titration may increase the dose every 4 days. Do not exceed maximum daily dose of 26 mg (13 mg twice daily). Patients who are taking stiripentol: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, if tolerated, can increase dose to 0.2 mg/kg twice daily (0.4 mg/kg/day), which is the recommended maintenance dose.

需要更快滴定的患者可以每4天增加一次剂量。每日最大剂量不得超过26毫克（每日两次，每次13毫克）。正在服用司替戊醇的患者：起始剂量为每日两次0.1毫克/千克（每日0.2毫克/千克）。7天后，如果耐受良好，可将剂量增加至每日两次0.2毫克/千克（每日0.4毫克/千克），这是推荐的维持剂量。

Patients requiring more rapid titration may increase the dose every 4 days. Do not exceed a total dose of 17 mg (8.6 mg twice daily). Lennox-Gastaut syndrome: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, the dose should be increased to 0.2 mg/kg twice daily (0.4 mg/kg/day), if tolerated.

需要更快滴定的患者可每4天增加一次剂量。总剂量不得超过17毫克（每日两次8.6毫克）。Lennox-Gastaut综合征：起始剂量为每日两次0.1毫克/千克（每日0.2毫克/千克）。如果耐受良好，7天后剂量应增加至每日两次0.2毫克/千克（每日0.4毫克/千克）。

After an additional 7 days, if tolerated, dose should be increased to 0.35 mg/kg twice daily (0.7 mg/kg/day), which is the recommended maintenance dose. Do not exceed maximum daily dose of 26 mg (13 mg twice daily). Discontinuation: When discontinuing treatment, decrease the dose gradually. As with all anti-epileptic medicines, avoid abrupt discontinuation when possible to minimize the risk of increased seizure frequency and status epilepticus.

在额外的7天后，如果耐受良好，剂量应增加到每日两次0.35 mg/kg（每日总量0.7 mg/kg），这是推荐的维持剂量。每日最大剂量不得超过26 mg（每次13 mg，每日两次）。停药：停药时应逐渐减少剂量。与所有抗癫痫药物一样，尽可能避免突然停药，以减少癫痫发作频率增加和癫痫持续状态的风险。

A final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. Renal impairment: Generally, no dose adjustment is recommended when administered to patients with mild to severe renal impairment, however, a slower titration may be considered. If adverse reactions are rep.

应在芬氟拉明治疗的最后一剂后3-6个月进行最终的超声心动图检查。肾功能损害：一般来说，对于轻度至重度肾功能损害的患者，无需调整剂量，但可以考虑较慢的滴定速度。如果出现不良反应，请报告。

Contraindications

禁忌症

: Hypersensitivity to active substance or any excipients. Aortic or mitral valvular heart disease and pulmonary arterial hypertension. Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of serotonin syndrome.

对活性物质或任何辅料过敏者禁用。患有主动脉或二尖瓣心脏疾病及肺动脉高压者禁用。在使用单胺氧化酶抑制剂后14天内禁用，因其可能增加血清素综合征的风险。

Warnings and Precautions:

警告和注意事项：

Aortic or mitral valvular heart disease and pulmonary arterial hypertension: Prior to starting treatment, patients must undergo an echocardiogram to establish a baseline and exclude any pre-existing valvular heart disease or pulmonary hypertension. Conduct echocardiogram monitoring every 6 months for the first 2 years and annually thereafter.

主动脉或二尖瓣瓣膜性心脏病和肺动脉高压：在开始治疗前，患者必须接受超声心动图检查，以建立基线并排除任何先前存在的瓣膜性心脏病或肺动脉高压。在治疗的前2年，每6个月进行一次超声心动图监测，此后每年一次。

If an echocardiogram indicates pathological valvular changes, consider follow-up earlier to evaluate whether the abnormality is persistent. If pathological abnormalities seen on echocardiogram, evaluate the benefit versus risk of continuing fenfluramine treatment with the prescriber, caregiver and cardiologist.

如果超声心动图显示病理性瓣膜改变，应考虑提前进行随访，以评估该异常是否持续存在。若超声心动图上发现病理性异常，应与开处方的医生、护理人员和心脏病专家一起评估继续使用芬氟拉明治疗的益处与风险。

Once treatment is discontinued for any reasons, a final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. If echocardiogram findings suggestive of pulmonary arterial hypertension, perform a repeat echocardiogram as soon as possible and within 3 months to confirm these findings.

一旦因任何原因停止治疗，应在最后一次服用芬氟拉明后3-6个月内进行最终的超声心动图检查。如果超声心动图结果显示可能存在肺动脉高压，应尽快并在3个月内重复进行超声心动图以确认这些发现。

If echocardiogram finding is confirmed suggestive of an increased probability of pulmonary arterial hypertension defined as intermediate probability, conduct a benefit-risk evaluation of continuation of Fintepla by the prescriber, carer and cardiologist. If echocardiogram suggests a high probability, it is recommended fenfluramine treatment should be stopped.

如果超声心动图检查结果确认为中等概率的肺动脉高压可能性增加，处方医生、护理人员和心脏病专家应进行芬特帕（Fintepla）继续使用的风险效益评估。如果超声心动图显示高概率，建议停止芬氟拉明（fenfluramine）治疗。

Decreased appetite and weight loss: Fenfluramine can cause decreased appetite and weight loss - an additive effect can occur in combination with other anti-epileptic medicines such as stiripentol. Monitor the patient’s weight. Undertake risk-benefit evaluation before starting treatment if history of anorexia nervosa or bulimia nervosa.

食欲下降和体重减轻：芬氟拉明可能引起食欲下降和体重减轻——与其它抗癫痫药物（如司替戊醇）合用时可能会产生叠加效应。监测患者的体重。如果患者有神经性厌食症或神经性贪食症病史，在开始治疗前进行风险收益评估。

Fintepla controlled access programme: A controlled access programme has been created to 1) prevent off-label use i.

芬特普拉控制访问计划：已创建一个控制访问计划，以1）防止标签外使用。

efficacy may be reduced. Glaucoma: Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Discontinue therapy in patients with acute decreases in visual acuity. Consider discontinuation if ocular pain of unknown origin. Effect of CYP1A2 or CYP2B6 inducers: Co-administration with strong CYP1A2 inducers or CYP2B6 inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of fenfluramine.

疗效可能会降低。青光眼：芬氟拉明可引起瞳孔散大，并可能诱发闭角型青光眼。若患者出现急性视力下降，应停止治疗。若出现不明原因的眼痛，考虑停药。CYP1A2或CYP2B6诱导剂的影响：与强效CYP1A2诱导剂或CYP2B6诱导剂联合使用会降低芬氟拉明的血浆浓度，这可能会降低芬氟拉明的疗效。

If co-administration is considered necessary, the patient should be monitored for reduced efficacy and a dose increase of fenfluramine could be considered provided that it does not exceed twice the.

如果认为联合给药是必要的，应监测患者是否出现疗效降低，并且在不超过两倍剂量的前提下，可以考虑增加芬氟拉明的剂量。

maximum daily dose (52 mg/day). If a strong CYP1A2 or CYP2B6 inducer is discontinued during maintenance treatment with fenfluramine, consider gradual reduction of the fenfluramine dosage to the dose administered prior to initiating the inducer. Effect of CYP1A2 or CYP2D6 inhibitors: Initiation of concomitant treatment with a strong CYP1A2 or CYP2D6 inhibitor may result in higher exposure and, therefore, adverse events should be monitored, and a dose reduction may be needed in some patients.

最大日剂量（52毫克/天）。如果在使用芬氟拉明维持治疗期间停用强效CYP1A2或CYP2B6诱导剂，考虑逐步减少芬氟拉明的剂量至诱导剂开始前的剂量。CYP1A2或CYP2D6抑制剂的影响：与强效CYP1A2或CYP2D6抑制剂同时开始治疗可能会导致更高的暴露量，因此应监测不良事件，并且部分患者可能需要减少剂量。

Excipients: Contains sodium ethyl para-hydroxybenzoate (E 215) and sodium methyl para-hydroxybenzoate (E 219) - may cause allergic reactions.

辅料：含乙基对羟基苯甲酸钠（E 215）和甲基对羟基苯甲酸钠（E 219）- 可能引起过敏反应。

(possibly delayed). It also contains sulfur dioxide (E 220) which may rarely cause severe hypersensitivity reactions and bronchospasm. Patients with rare glucose-galactose malabsorption should not take this medicine. The product contains less than 1 mmol sodium (23 mg) per the maximum daily dose of 12 mL; essentially ‘sodium-free’.

（可能延迟）。它还含有二氧化硫 (E 220)，这种成分可能极少数情况下会引起严重的过敏反应和支气管痉挛。患有罕见的葡萄糖-半乳糖吸收不良的患者不应服用此药。该产品在每日最大剂量12毫升中含有不到1毫摩尔钠（23毫克），基本上“无钠”。

Contains glucose - may be harmful to teeth. Interactions: Pharmacodynamic interactions with other CNS depressants increase the risk of aggravated central nervous system depression. An.

含有葡萄糖——可能对牙齿有害。相互作用：与其他中枢神经系统抑制剂的药效学相互作用会增加中枢神经系统抑制加重的风险。

increase in dose may be necessary when coadministered with rifampicin or a strong CYP1A2 or CYP2B6 inducer. In in vitro studies coadministration with a strong CYP1A2 or CYP2D6 inhibitor may result in higher exposure (see section 4.4 of the SmPC). Coadministration with CYP2D6 substrates or MATE1 substrates may increase their plasma concentrations.

当与利福平或强效CYP1A2或CYP2B6诱导剂联合使用时，可能需要增加剂量。在体外研究中，与强效CYP1A2或CYP2D6抑制剂联合使用可能导致更高的暴露量（见SmPC第4.4节）。与CYP2D6底物或MATE1底物联合使用可能会增加其血浆浓度。

Co-administration with CYP2B6 or CYP3A4 substrates may decrease their plasma concentrations. Pregnancy and lactation: Limited data in pregnant women. As a precaution, avoid use of Fintepla in pregnancy. It is unknown whether fenfluramine/metabolites are excreted in human milk. Animal.

与CYP2B6或CYP3A4底物共同给药可能会降低其血浆浓度。妊娠和哺乳：孕妇中的数据有限。作为预防措施，避免在妊娠期间使用Fintepla。目前尚不清楚芬氟拉明/代谢物是否排泄到人乳中。动物。

data have shown excretion of fenfluramine/metabolites in milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Fintepla taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Drive and use machines.: Fintepla has moderate influence on the ability to drive/ use machines as it may cause somnolence and fatigue.

数据显示芬氟拉明/代谢物会排泄到乳汁中。必须权衡母乳喂养对婴儿的益处以及治疗对妇女的益处，从而决定是否停止母乳喂养或停止/避免使用Fintepla。驾驶和操作机器：Fintepla对驾驶/操作机器的能力有中等影响，因为它可能引起嗜睡和疲劳。

Advise patients not to drive or operate machinery until they have sufficient experience to gauge whether it adversely.

建议患者在没有足够经验来判断是否会产生不良影响之前，不要驾驶或操作机器。

affects their abilities. Pulmonary arterial hypertension: pulmonary arterial hypertension in a child associated with fenfluramine for Dravet syndrome has been reported post-marketing. The patient discontinued fenfluramine and the reaction resolved post-discontinuation. Valvular heart disease: valvular heart disease in a child associated with fenfluramine for Dravet syndrome has also been reported post-marketing (see Adverse effects: Dravet syndrome: Very common (≥1/10): Upper respiratory tract infection, decreased appetite, somnolence, diarrhoea, pyrexia, fatigue, blood glucose decreased, echocardiogram abnormal (Consisted of trace and mild mitral regurgitation, and trace aortic regurgitation, which are considered physiologic).

影响他们的能力。肺动脉高压：有报道指出，服用芬氟拉明治疗Dravet综合征的儿童在上市后出现了肺动脉高压。患者停用芬氟拉明后，反应在停药后消除。心脏瓣膜病：也有报道指出，服用芬氟拉明治疗Dravet综合征的儿童在上市后出现心脏瓣膜病（见不良反应：Dravet综合征：很常见（≥1/10）：上呼吸道感染、食欲减退、嗜睡、腹泻、发热、疲劳、血糖降低、超声心动图异常（包括微量和轻度二尖瓣反流及微量主动脉反流，这些均被视为生理性的）。

Common (≥1/100 to <1/10): Bronchitis, abnormal behaviour, aggression, agitation, insomnia, mood swings, ataxia, hypotonia, lethargy, seizure, status epilepticus, tremor, constipation, salivary hypersecretion, weight decreased and blood prolactin increased. Lennox-Gastaut syndrome: Very common (≥1/10): Upper respiratory tract infection, decreased appetite, somnolence, diarrhoea, vomiting, fatigue.

常见（≥1/100 至 <1/10）：支气管炎、异常行为、攻击性、激动、失眠、情绪波动、共济失调、肌张力减退、嗜睡、癫痫发作、癫痫持续状态、震颤、便秘、唾液分泌过多、体重减轻和催乳素升高。Lennox-Gastaut 综合征：很常见（≥1/10）：上呼吸道感染、食欲下降、嗜睡、腹泻、呕吐、疲劳。

Common (≥1/100 to <1/10): Bronchitis, influenza, pneumonia, seizure, status epilepticus, lethargy, tremor, constipation, salivary hypersecretion, blood prolactin increased, weight decreased, fall. Refer to SmPC for other adverse reactions. .

常见（≥1/100 至 <1/10）：支气管炎、流感、肺炎、癫痫发作、癫痫持续状态、嗜睡、震颤、便秘、唾液分泌过多、血液催乳素升高、体重减轻、跌倒。其他不良反应请参阅 SmPC。

▼

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

本药品将受到额外的监测。这将有助于快速识别新的安全信息。医疗专业人员被要求报告任何可疑的不良反应。

Refer to the European Summary of Product Characteristics for other adverse reactions and full Prescribing Information.

请参阅欧洲产品特性总结中的其他不良反应和完整的处方信息。

https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf

(accessed October 2024)

（访问于2024年10月）

Important Safety Information about FINTEPLA® (fenfluramine) in the US

美国关于FINTEPLA®（芬氟拉明）的重要安全信息

FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older

FINTEPLA 适用于治疗 2 岁及以上患者的 Dravet 综合征和 Lennox-Gastaut 综合征相关的癫痫发作。

FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS. Further information is available at

FINTEPLA 仅通过名为 FINTEPLA REMS 的受限分销计划提供。更多信息可访问

www.FinteplaREMS.com

or by telephone at +1 877 964 3649.

或通过电话拨打 +1 877 964 3649。

IMPORTANT SAFETY INFORMATION

重要的安全信息

BOXED WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION

黑框警告：瓣膜性心脏病和肺动脉高压

There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease and pulmonary arterial hypertension.

5-HT2B受体激动剂活性的血清素能药物，包括芬氟拉明（FINTEPLA中的活性成分），与心脏瓣膜病和肺动脉高压之间存在关联。

Echocardiogram assessments are required before, during, and after treatment with FINTEPLA.

在使用FINTEPLA治疗之前、期间和之后，都需要进行超声心动图评估。

FINTEPLA is available only through a restricted program called the FINTEPLA REMS.

FINTEPLA 仅通过名为 FINTEPLA REMS 的限制性计划提供。

CONTRAINDICATIONS

禁忌症

Hypersensitivity to fenfluramine or any of the excipients in FINTEPLA. Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of serotonin syndrome.

对芬氟拉明或FINTEPLA中的任何辅料过敏者禁用。在使用单胺氧化酶抑制剂的14天内，由于血清素综合征的风险增加，也应避免使用。

WARNINGS AND PRECAUTIONS

警告和注意事项

Decreased Appetite and Decreased Weight: Advise patients that FINTEPLA can cause decreased appetite and decreased weight. Somnolence, Sedation, and Lethargy: Monitor for somnolence and sedation. Advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA.

食欲减退和体重减轻：告知患者FINTEPLA可能引起食欲减退和体重减轻。嗜睡、镇静和倦怠：监测嗜睡和镇静情况。建议患者在对FINTEPLA有足够的使用经验之前，不要驾驶或操作机械。

Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and thoughts. Withdrawal of Antiepileptic Drugs: FINTEPLA should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus. Serotonin Syndrome: Advise patients that serotonin syndrome is a potentially life-threatening condition and may occur with FINTEPLA, particularly with concomitant administration of FINTEPLA with other serotonergic drugs.

自杀行为和意念：监测患者的自杀行为和念头。抗癫痫药物的停药：应逐渐减少FINTEPLA的剂量，以尽量减少癫痫发作频率增加和癫痫持续状态的风险。血清素综合症：告知患者血清素综合症是一种可能危及生命的状况，使用FINTEPLA时可能会发生，特别是与其它影响血清素的药物同时使用时。

Increase in Blood Pressure: Monitor blood pressure during treatment. Glaucoma: Discontinue therapy in patients with acute decrease in visual acuity or ocular pain. .

血压升高：治疗期间监测血压。青光眼：对于视力急性下降或眼部疼痛的患者，停止治疗。

ADVERSE REACTIONS

不良反应

The most common adverse reactions (incidence at least 10% and greater than placebo) in patients with Dravet Syndrome were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus.

Dravet综合征患者最常见的不良反应（发生率至少为10%且高于安慰剂）包括食欲下降；嗜睡、镇静、乏力；腹泻；便秘；心电图异常；疲劳、不适、虚弱；共济失调、平衡障碍、步态异常；血压升高；流涎、唾液分泌过多；发热；上呼吸道感染；呕吐；体重减轻；跌倒；癫痫持续状态。

The most common adverse reactions (incidence at least 10% and greater than placebo) in patients with Lennox-Gastaut syndrome were diarrhea; decreased appetite; fatigue; somnolence; vomiting. .

Lennox-Gastaut综合征患者最常见的不良反应（发生率至少10%且高于安慰剂）为腹泻、食欲减退、疲劳、嗜睡和呕吐。

DRUG INTERACTIONS

药物相互作用

Strong CYP1A2, CYP2B6, or CYP3A Inducers: Coadministration with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed.

强效CYP1A2、CYP2B6或CYP3A诱导剂：与强效CYP1A2、CYP2B6或CYP3A诱导剂联合使用会降低芬氟拉明的血浆浓度。如果必须将强效CYP1A2、CYP2B6或CYP3A诱导剂与FINTEPLA联合使用，需监测患者是否出现疗效降低，并根据需要考虑增加FINTEPLA的剂量。

If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer. .

如果在使用FINTEPLA进行维持治疗期间停用强效CYP1A2、CYP2B6或CYP3A诱导剂，考虑将FINTEPLA的剂量逐渐减少至诱导剂开始前的剂量。

Strong CYP1A2 or CYP2D6 Inhibitors: Coadministration with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations. If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg. If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors.

强效CYP1A2或CYP2D6抑制剂：与强效CYP1A2或CYP2D6抑制剂联合使用会增加芬氟拉明的血浆浓度。如果FINTEPLA与强效CYP1A2或CYP2D6抑制剂联合使用，FINTEPLA的最大日剂量为20毫克。如果在使用FINTEPLA维持治疗期间停用强效CYP1A2或CYP2D6抑制剂，考虑逐步增加FINTEPLA的剂量至未使用CYP1A2或CYP2D6抑制剂时推荐的剂量。

If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, the maximum daily dosage of FINTEPLA is 17 mg. .

如果 FINTEPLA 与斯特里潘托尔和强效 CYP1A2 或 CYP2D6 抑制剂联合使用，FINTEPLA 的每日最大剂量为 17 毫克。

Coadministration of FINTEPLA with stiripentol plus clobazam, with or without valproate, increases fenfluramine plasma concentrations. If FINTEPLA is coadministered with stiripentol plus clobazam, the maximum daily dosage of FINTEPLA is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg).

与司替戊醇和氯巴占（无论是否与丙戊酸合用）共同给药时，会增加芬氟拉明的血浆浓度。如果FINTEPLA与司替戊醇和氯巴占共同给药，FINTEPLA的每日最大剂量为0.2 mg/kg，每日两次（每日最大剂量为17 mg）。

USE IN SPECIFIC POPULATIONS

在特定人群中使用

There are no data on FINTEPLA use in pregnant women. Available data from epidemiologic studies with fenfluramine or dexfenfluramine are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. FINTEPLA can cause decreased appetite and decreased weight, monitor for adequate weight gain during pregnancy.

目前尚无关于孕期妇女使用FINTEPLA的数据。现有的关于芬氟拉明或右芬氟拉明的流行病学研究数据不足以评估药物相关的重大出生缺陷、流产或其他不良母体或胎儿结局的风险。FINTEPLA可能引起食欲减退和体重下降，孕期应监测体重是否适当增加。

In animal studies, administration of fenfluramine throughout organogenesis (rat and rabbit) or throughout gestation and lactation (rat) resulted in adverse effects on development (fetal malformations, embryofetal and offspring mortality and growth impairment) in the presence of maternal toxicity at clinically relevant maternal plasma levels of fenfluramine and its major active metabolite.

在动物研究中，在器官发生期（大鼠和兔子）或整个妊娠期和哺乳期（大鼠）给予芬氟拉明，会在母体毒性存在的情况下，对发育产生不良影响（胎儿畸形、胚胎胎仔和后代死亡率增加以及生长受损），此时芬氟拉明及其主要活性代谢物的母体血浆水平与临床相关。

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. .

指明人群的主要出生缺陷和流产的估计背景风险尚不清楚。所有妊娠都有出生缺陷、流产或其他不良后果的背景风险。在美国普通人群中，临床确认妊娠的主要出生缺陷和流产的估计背景风险分别为2%至4%和15%至20%。

References

参考文献

Specchio N, Marsh E, Devinsky O, et al. Fenfluramine in CDKL5 deficiency disorder: primary efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. AES. 2025. Abstract number: TBC.

Specchio N, Marsh E, Devinsky O, 等。芬氟拉明在CDKL5缺乏症中的应用：来自一项三期随机双盲安慰剂对照研究的主要疗效和安全性结果。AES. 2025. 摘要编号：待定。

ClinicalTrials.gov. NCT05064878. Available at:

ClinicalTrials.gov. NCT05064878. 可在：

https://clinicaltrials.gov/study/NCT05064878

. Accessed: September 2025.

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