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

默克，一家领先的科技公司，今天宣布欧洲委员会（EC）已授予OGSIVEO上市许可。

(nirogacestat), an oral gamma secretase inhibitor, as monotherapy for the treatment of adults with progressing desmoid tumors who require systemic treatment. OGSIVEO is the first and only therapy approved in the European Union (EU) to treat desmoid tumors. The approval was issued to SpringWorks Therapeutics Inc., a healthcare company of Merck..

(nirogacestat)，一种口服的γ分泌酶抑制剂，作为单药治疗需要全身治疗的进展性硬纤维瘤成人患者。OGSIVEO是欧盟（EU）首个也是唯一获批用于治疗硬纤维瘤的疗法。该批准由默克旗下的医疗公司SpringWorks Therapeutics Inc.获得。

“Desmoid tumors can have a profound impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence. Until now, there have been no approved medicines in Europe,” said Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial.

“硬纤维瘤可以对人们的生活产生深远的影响，由于其侵袭性和高复发率，管理起来非常困难。到目前为止，欧洲尚无获批的药物，”德国海德堡大学曼海姆癌症中心教授、DeFi 试验的首席研究员 Bernd Kasper 医学博士说道。

“OGSIVEO is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms, including a significant reduction in pain which is the most debilitating symptom reported by patients.”.

“OGSIVEO 是一种高度创新的疗法，其疗效数据显示出显著的抗肿瘤活性，并且在硬纤维瘤症状方面有显著改善，包括显著减轻患者报告的最令人虚弱的症状——疼痛。”

“This approval is a long-awaited advance for desmoid tumor patients, their families and physicians in Europe,” said Lynne Hernandez, Executive Director of the Desmoid Tumor Research Foundation. “It is our hope that patients will benefit from greater awareness of desmoid tumors, faster diagnoses, and better outcomes now that there is an approved treatment.”.

“这一批准是欧洲硬纤维瘤患者、他们的家人和医生期待已久的进展，”硬纤维瘤研究基金会执行董事林恩·埃尔南德斯表示。“我们希望现在有了获批的治疗方法，患者将从对硬纤维瘤更高的认知度、更快的诊断和更好的治疗结果中受益。”

Desmoid tumors are rare, locally aggressive tumors that form in the connective tissues of the body.

硬纤维瘤是罕见的、局部侵袭性肿瘤，形成于人体的结缔组织中。

Approximately 1,300 to 2,300 new cases of desmoid tumors are diagnosed annually in the EU.

欧盟每年大约诊断出1300至2300例新的硬纤维瘤病例。

These tumors can cause severe pain, limited function, loss of mobility, disfigurement and fatigue.

这些肿瘤可能导致剧烈疼痛、功能受限、行动能力丧失、畸形和疲劳。

They are challenging to manage because of their unpredictable nature and high rate of recurrence, which can significantly impact an individual’s quality of life.

由于它们的不可预测性和高复发率，管理起来颇具挑战性，这可能会显著影响个人的生活质量。

Desmoid tumor experts and treatment guidelines now recommend medical therapy as first-line intervention instead of surgery for most tumor locations requiring treatment.

硬纤维瘤专家和治疗指南现在推荐药物治疗作为大多数需要治疗的肿瘤位置的首选干预措施，而不是手术。

“We would like to extend our gratitude to the patients, families, investigators, and advocacy organizations who helped make this EC approval possible,” said Danny Bar-Zohar, MD, CEO of Healthcare and Executive Board Member at Merck. “OGSIVEO is already established as the standard of care systemic therapy for desmoid tumors in the U.S., and our goal is to bring the same treatment benefits to patients in Europe.

“我们谨向帮助实现这一EC批准的患者、家属、研究人员和倡导组织表示感谢，”默克公司医疗保健首席执行官兼执行董事会成员Danny Bar-Zohar博士说道。“OGSIVEO已在美国确立为治疗硬纤维瘤的标准系统疗法，我们的目标是为欧洲的患者带来同样的治疗益处。”

Following last month’s EC approval of our therapy for patients with NF1-PN, we are in the unique position of launching two innovative treatments - underscoring our commitment to the rare tumor patient community.”.

“继上个月欧洲委员会批准我们针对NF1-PN患者的治疗后，我们正处于推出两种创新疗法的独特位置——这凸显了我们对罕见肿瘤患者群体的承诺。”

The EC approval of OGSIVEO is based on results from the Phase 3 DeFi trial, which enrolled 142 adult patients with progressing desmoid tumors and met the primary endpoint of improving progression-free survival (PFS). OGSIVEO demonstrated a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001).

欧洲委员会批准OGSIVEO是基于三期DeFi试验的结果，该试验招募了142名患有进展性硬纤维瘤的成年患者，并达到了改善无进展生存期（PFS）的主要终点。OGSIVEO显示出比安慰剂统计学上显著的改善，疾病进展风险降低了71%（风险比（HR）= 0.29 （95%置信区间：0.15, 0.55）；p< 0.001）。

OGSIVEO also demonstrated a significant improvement in objective response rate (ORR). The confirmed ORR based on RECIST v1.1 was 41% with OGSIVEO versus 8% with placebo (p<0.001); the complete response rate was 7% in the OGSIVEO arm and 0% in the placebo arm. The median time to first response was 5.6 months with OGSIVEO and 11.1 months with placebo.

OGSIVEO 还展示了客观缓解率（ORR）的显著提升。根据 RECIST v1.1 确认的 ORR 在 OGSIVEO 组为 41%，而安慰剂组为 8%（p<0.001）；OGSIVEO 组的完全缓解率为 7%，安慰剂组为 0%。OGSIVEO 组的中位首次缓解时间为 5.6 个月，而安慰剂组为 11.1 个月。

Additionally, OGSIVEO demonstrated early and sustained improvement in patient-reported outcomes (PROs), including pain (p<0.001), desmoid tumor-specific symptoms (p<0.001), physical/role functioning (p<0.001), and overall health-related quality of life (p≤0.01)..

此外，OGSIVEO 在患者报告的结果 (PRO) 方面表现出早期且持续的改善，包括疼痛 (p<0.001)、侵袭性纤维瘤病特异性症状 (p<0.001)、身体/角色功能 (p<0.001) 以及整体健康相关生活质量 (p≤0.01)。

OGSIVEO exhibited a manageable safety and tolerability profile. The most common adverse reactions reported in 88 patients receiving OGSIVEO across all studies (69 patients from DeFi and 19 patients from early phase studies) were diarrhea (85%), rash (65%), ovarian toxicity in women of childbearing potential (60%) nausea (59%), fatigue (50%), hypophosphataemia (50%), headache (40%) and stomatitis (40%)..

OGSIVEO表现出可控的安全性和耐受性。在所有研究中，接受OGSIVEO的88名患者（其中69名来自DeFi研究，19名来自早期阶段研究）报告的最常见不良反应为腹泻（85%）、皮疹（65%）、育龄女性卵巢毒性（60%）、恶心（59%）、疲劳（50%）、低磷血症（50%）、头痛（40%）和口腔炎（40%）。

About the DeFi Trial

关于 DeFi 试验

DeFi (

去中心化金融 (

NCT03785964

NCT03785964

) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily.

）是一项全球性、随机（1:1）、多中心、双盲、安慰剂对照的关键性3期试验，评估了尼罗格司他（nirogacestat）在进展型硬纤维瘤成年患者中的疗效、安全性和耐受性。研究的双盲阶段随机分配了142名患者（尼罗格司他组，n=70；安慰剂组，n=72），接受每日两次150毫克的尼罗格司他或安慰剂治疗。

Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate, duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes.

关键的入选标准包括在筛选前12个月内，根据实体瘤疗效评价标准（RECIST 1.1）测量肿瘤进展≥20%。主要终点是由盲态独立中心评审评估的无进展生存期或任何原因导致的死亡。次要和探索性终点包括安全性与耐受性指标、客观缓解率、缓解持续时间、通过磁共振成像（MRI）评估的肿瘤体积变化以及患者报告结果的变化。

DeFi also included an open-label extension phase..

DeFi 还包括一个开放标签的扩展阶段。

About Desmoid Tumors

关于硬纤维瘤

Desmoid tumors are rare, locally aggressive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.

硬纤维瘤是罕见的、局部侵袭性的软组织肿瘤，可能严重致残，并且在极少数情况下，当重要结构受到影响时，可能危及生命。

1,2

1,2

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.

硬纤维瘤最常见于20至44岁之间的患者，女性患病率比男性高两到三倍。

3,11

3,11

It is estimated that there are 1,300-2,300 new desmoid tumor cases diagnosed per year in the European Union.

据估计，欧盟每年新增1300至2300例硬纤维瘤病例。

3,4,5

3，4，5

Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.

虽然硬纤维瘤不会发生转移，但手术切除后仍可能伴随高达77%的复发率。

11,12

11，12

Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.

硬纤维瘤专家和治疗指南现在推荐系统性治疗作为大多数需要治疗的肿瘤位置的首选干预措施。

About OGSIVEO

关于OGSIVEO

OGSIVEO (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States and European Union as monotherapy for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

OGSIVEO(nirogacestat) 是一种口服、选择性的小分子γ分泌酶抑制剂，在美国和欧盟获批作为单药疗法，用于治疗需要系统性治疗的进展性硬纤维瘤成年患者。

The FDA and the EMA have granted Orphan Drug designation for OGSIVEO for the treatment of desmoid tumors.

美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）已授予OGSIVEO用于治疗硬纤维瘤的孤儿药资格。

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个也是唯一获得FDA批准的用于治疗成人硬纤维瘤的药物，以及首个也是唯一获批用于治疗成人和儿童1型神经纤维瘤病相关丛状神经纤维瘤（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其他罕见肿瘤和血液癌症患者的新靶向治疗产品候选药物。