EZMEKLY is the first and only therapy to receive marketing authorization in the EU for both adults and children (≥2 years) with NF1-PN, a rare genetic disorder with debilitating symptoms

EZMEKLY 是首个也是唯一一个在欧盟获得批准用于治疗患有 NF1-PN 的成人和儿童（≥2 岁）的疗法，NF1-PN 是一种罕见的遗传性疾病，症状令人虚弱。

Merck, a leading science and technology company, announced today that the European Commission (EC) granted conditional marketing authorization for EZMEKLY

默克公司，一家领先的科学和技术公司，今天宣布欧洲委员会（EC）授予EZMEKLY有条件营销授权。

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(mirdametinib) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above. EZMEKLY is the first and only therapy approved in the European Union (EU) for both adults and children with NF1-PN. The approval was issued to SpringWorks Therapeutics Inc., a healthcare company of Merck..

（米达美替尼）用于治疗2岁及以上患有1型神经纤维瘤病（NF1）的儿童和成人患者的症状性、不可手术的丛状神经纤维瘤（PN）。EZMEKLY是首个也是唯一一个在欧盟（EU）获批用于治疗成人和儿童NF1-PN的疗法。该批准由默克旗下的医疗公司SpringWorks Therapeutics Inc.获得。

“Patients with NF1-PN often face physical and mental health challenges and impaired quality of life given the limited treatment options available for this lifelong and debilitating disease,” said Ignacio Blanco, MD, PhD, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol, Spain.

“鉴于这种终身且致残的疾病可用的治疗方案有限，NF1-PN 患者常常面临身体和心理健康方面的挑战，生活质量也受到损害，”西班牙 Hospital Universitari Germans Trias i Pujol 的国家成人神经纤维瘤病参考中心主任 Ignacio Blanco 医学博士表示。

“This approval represents an important advance, especially for adults who previously did not have an approved treatment. In clinical trials, EZMEKLY demonstrated an encouraging efficacy and safety profile in both adults and children, and importantly, is available in a tablet that dissolves easily in water for people who are unable to swallow a pill and could therefore not previously receive therapy.”.

“此次获批代表了重要的进展，特别是对于之前没有获批治疗方案的成年人。在临床试验中，EZMEKLY 在成人和儿童中均显示出令人鼓舞的有效性和安全性，更重要的是，该药有可轻松溶于水的片剂，适合无法吞咽药丸的人群，他们因此前无法接受治疗。”

“This European Commission approval is an important milestone for NF patients and caregivers, as it means more treatment options for patients with plexiform neurofibromas, including adults,” said Annette Bakker, PhD, Chief Executive Officer of the Children’s Tumor Foundation (CTF) and Dariusz Adamczewski, MD, Director CTF Europe.

“这一欧洲委员会的批准对于NF患者和护理人员来说是一个重要的里程碑，因为它意味着丛状神经纤维瘤患者，包括成年人，将有更多的治疗选择，”儿童肿瘤基金会（CTF）首席执行官安妮特·巴克尔博士和CTF欧洲总监达里乌什·亚当采夫斯基医学博士表示。

“This is the kind of progress that happens when researchers, industry and organizations like ours work together with a shared focus on delivering new treatments for patients.”.

“当研究人员、行业和像我们这样的组织共同努力，专注于为患者提供新的治疗方法时，就会取得这样的进展。”

“Bringing innovation to patients living with rare tumors around the world is a clear reflection of our focus on addressing significant unmet needs and transforming outcomes for patients and their families,” said Jan Kirsten, Global Head of Rare Tumor Business at the Healthcare business sector of Merck.

“为全球罕见肿瘤患者带来创新，这明确反映了我们致力于解决重大未满足需求，并为患者及其家庭改变结果的承诺，”默克医疗保健业务部门罕见肿瘤业务全球负责人扬·基尔斯滕表示。

“With the European approval of EZMEKLY, the first therapy approved for both adults and children with NF1-PN, we are taking a major step toward improving care for this underserved community and are committed to making our medicine available to eligible NF1-PN patients across Europe as quickly as possible.”.

“随着EZMEKLY在欧洲的获批，这是首个获准用于治疗成人和儿童NF1-PN的疗法，我们在改善这一服务不足群体的护理方面迈出了重要一步，并致力于尽快将我们的药物提供给欧洲所有符合条件的NF1-PN患者。”

NF1 is a genetic disorder that affects approximately 3 in 10,000 people in the EU, or an estimated 135,000 people. Among patients with NF1, the lifetime risk of developing plexiform neurofibromas is approximately 30% to 50%. These tumors grow in an infiltrative pattern along the peripheral nerve sheath and can cause severe disfigurement, pain and functional impairment.

NF1是一种遗传性疾病，影响欧盟约万分之三的人口，估计有13.5万人。在NF1患者中，一生中患丛状神经纤维瘤的风险约为30%至50%。这些肿瘤沿周围神经鞘以浸润性方式生长，可能导致严重畸形、疼痛和功能障碍。

Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.5 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection..

丛状神经纤维瘤可转变为恶性外周神经鞘瘤，这是一种侵袭性且可能致命的疾病。由于丛状神经纤维瘤沿神经浸润性生长，手术切除可能具有挑战性，并且约85%的丛状神经纤维瘤被认为无法完全切除。

The EC approval of EZMEKLY is based on results from the ongoing, multi-center, open-label, single arm Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN age 2 years or older (58 adults and 56 pediatric patients). The study met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating an ORR of 41% (N= 24/58) in adults and 52% in children (N=29/56).

欧盟对EZMEKLY的批准是基于正在进行的多中心、开放标签、单臂2b期ReNeu试验的结果，该试验招募了114名2岁或以上患有NF1-PN的患者（58名成人和56名儿童患者）。研究达到了由盲法独立中央审查评估的主要终点——确认的客观缓解率（ORR），在成人中显示出41%的ORR（N=24/58），在儿童中为52%（N=29/56）。

The median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children. Among those with a confirmed response, 88% percent of adults and 90% of children had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration.

成人目标 PN 体积的最佳百分比变化中位数为 -41%（范围：-90% 至 13%），儿童为 -42%（范围：-91% 至 48%）。在确认有反应的患者中，88% 的成人和 90% 的儿童反应持续至少 12 个月，而 50% 的成人和 48% 的儿童反应持续至少 24 个月。

Both adults and children also experienced early and sustained significant improvements from baseline in pain and quality of life as assessed across multiple patient-reported outcome tools..

成人和儿童在疼痛和生活质量方面也经历了从基线开始的早期且持续的显著改善，这些改善是通过多种患者报告的结果工具评估得出的。

EZMEKLY demonstrated a manageable safety and tolerability profile. The most common adverse reactions reported in adults receiving EZMEKLY were dermatitis acneiform (83%), diarrhea (55%), nausea (55%), blood creatine phosphokinase increased (47%), musculoskeletal pain (41%), vomiting (37%) and fatigue (36%).

EZMEKLY展示了可控的安全性和耐受性特征。在接受EZMEKLY治疗的成人中，最常见的不良反应为痤疮样皮炎（83%）、腹泻（55%）、恶心（55%）、血液肌酸磷酸激酶升高（47%）、肌肉骨骼疼痛（41%）、呕吐（37%）和疲劳（36%）。

The most common adverse reactions occurring in children were blood creatine phosphokinase increased (59%), diarrhea (53%), dermatitis acneiform (43%), musculoskeletal pain (41%), abdominal pain (40%), vomiting (40%), and headache (36%)..

儿童中最常见的不良反应为血肌酸磷酸激酶升高（59%）、腹泻（53%）、痤疮样皮炎（43%）、肌肉骨骼疼痛（41%）、腹痛（40%）、呕吐（40%）和头痛（36%）。

About the ReNeu Trial

关于ReNeu试验

ReNeu (NCT03962543) is an ongoing, multi-center, open-label, single arm, Phase 2b trial evaluating the efficacy, safety and tolerability of mirdametinib in patients ≥2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food.

ReNeu（NCT03962543）是一项正在进行的多中心、开放标签、单臂的IIb期试验，评估了Mirdametinib在≥2岁的因不可手术的NF1相关PN导致显著发病率的患者中的疗效、安全性和耐受性。该研究共招募了114名患者，接受每日两次剂量为2 mg/m²的Mirdametinib治疗（每日两次最大剂量为4 mg），不考虑食物影响。

Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate (ORR) defined as the proportion of patients with a ≥20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by MRI and assessed by blinded independent central review.

Mirdametinib以口服方式给药，采用3周服药、1周停药的给药方案，剂型为胶囊或分散片。主要终点是确认的客观缓解率（ORR），定义为在24个治疗周期内，连续扫描显示目标肿瘤体积减少≥20%的患者比例，通过MRI测量并由盲态独立中心评审评估。

Secondary endpoints include safety and tolerability, duration of response, and changes in patient-reported outcomes from baseline to Cycle 13. The treatment phase of the trial is complete, and results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow-up portion of the study, which is ongoing..

次要终点包括安全性与耐受性、反应持续时间以及从基线到第13周期患者报告结果的变化。试验的治疗阶段已经完成，结果在2024年美国临床肿瘤学会（ASCO）年会上公布。完成治疗阶段的患者有资格继续参与研究中可选的长期随访部分，该部分仍在进行中。

About NF1-PN

关于NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.10,11 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals.3,12 In the EU, NF1 affects approximately 3 in 10,000 people, or an estimated 135,000 people.1,2 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.1.

1型神经纤维瘤病（NF1）是一种罕见的遗传性疾病，由NF1基因突变引起，该基因编码神经纤维蛋白，这是MAPK通路的关键抑制因子。NF1是最常见的神经纤维瘤病形式，估计全球出生发病率为约2500人中有1人。在欧盟，NF1影响约每10,000人中的3人，总计约135,000人。NF1的临床过程异质性很强，表现为多个器官系统的多种症状，包括异常色素沉着、骨骼畸形、肿瘤生长以及认知障碍等神经系统并发症。与普通人群相比，NF1患者的平均预期寿命减少8到15年。

Patients with NF have approximately a 30% to 50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.3,4,5 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.14,15.

NF患者终生患丛状神经纤维瘤（plexiform neurofibromas，PN）的风险约为30%至50%，这是一种沿外周神经鞘以浸润模式生长的肿瘤，可能导致严重毁容、疼痛和功能障碍；在极少数情况下，NF1-PN可能是致命的。NF1-PN通常在生命的前二十年内被诊断出。这些肿瘤可能具有侵袭性，并与临床上显著的发病率相关；通常在儿童时期增长更快。

Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.5 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8

由于这些肿瘤沿神经浸润性生长，手术切除可能会很困难，并可能导致永久性神经损伤和畸形。大约85%的丛状神经纤维瘤被认为无法完全切除。

About GOMEKLI®/ EZMEKLY® (mirdametinib)

关于GOMEKLI®/ EZMEKLY®（米达美替尼）

GOMEKLI® (mirdametinib) is an oral, small molecule MEK inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection..

GOMEKLI®（米达美替尼）是一种口服的小分子MEK抑制剂，已获美国食品和药物管理局（FDA）批准，用于治疗2岁及以上患有1型神经纤维瘤病（NF1）且伴有无法完全切除的症状性丛状神经纤维瘤（PN）的成人和儿童患者。

Mirdametinib is marketed under the brand name EZMEKLY® in the European Union and is conditionally approved by the European Commission (EC) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above..

Mirdametinib 在欧盟以品牌名 EZMEKLY® 销售，并已获得欧洲委员会（EC）的有条件批准，用于治疗 2 岁及以上患有 1 型神经纤维瘤病（NF1）的儿童和成人患者的症状性、不可手术的丛状神经纤维瘤（PN）。

The FDA and the EC have granted Orphan Drug designation for mirdametinib for the treatment of NF1.

FDA和EC已授予米达美替尼治疗NF1的孤儿药资格。

For the full list of side effects and restrictions with EZMEKLY, see the full

有关EZMEKLY的完整副作用和限制列表，请参阅完整版

Summary of Product Characteristics

产品特性摘要

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About SpringWorks Therapeutics

关于SpringWorks Therapeutics

SpringWorks Therapeutics, a healthcare company of Merck, is a commercial-stage biopharmaceutical company dedicated to improving the lives of patients with rare tumors. We developed and are commercializing the first and only FDA-approved medicine for adults with desmoid tumors and the first and only approved medicine for both adults and children with neurofibromatosis type 1 associated plexiform neurofibromas (NF1-PN).

SpringWorks Therapeutics是默克旗下的一家医疗公司，是一家商业阶段的生物制药公司，致力于改善罕见肿瘤患者的生活。我们开发并正在商业化首款也是唯一一款获FDA批准用于治疗成人硬纤维瘤的药物，同时也是首款且唯一获批用于治疗成人和儿童1型神经纤维瘤病相关的丛状神经纤维瘤（NF1-PN）的药物。

We are also advancing a portfolio of novel targeted therapy product candidates for patients with additional rare tumors and hematological cancers..

我们还正在推进一系列针对更多罕见肿瘤和血液癌症患者的新靶向治疗产品候选药物。

For more information, visit www.springworkstx.com and follow @SpringWorksTx on X, LinkedIn, Facebook, Instagram and YouTube.

有关更多信息，请访问 www.springworkstx.com 并在 X、LinkedIn、Facebook、Instagram 和 YouTube 上关注 @SpringWorksTx。