Belzutifan

药械追踪 No.1 / 默沙东HIF-2α抑制剂贝组替凡获欧盟批准 2025年2月18日，默沙东宣布，贝组替凡（商品名：维利瑞/WELIREG）已获欧盟委员会（EC）批准，用于治疗：①不适合局部手术治疗的von Hippel-Lindau（VHL）病相关肾细胞癌（RCC）、中枢神经系统（CNS）血管母细胞瘤或胰腺神经内分泌肿瘤（pNET）成人患者；②既往接受过两种或多种PD-1/PD-L1抑制剂和至少两种VEGF靶向疗法后病情进展的成人晚期RCC患者。这是贝组替凡首次在欧盟获得批准。 VHL病，又称希佩尔-林道综合征、林岛综合征，是VHL抑癌基因突变引起的一种罕见常染色体显性遗传病。VHL病患者表现多器官肿瘤综合征，最常见的器官受累包括中枢神经系统血管母细胞瘤、肾细胞癌或肾囊肿、胰腺肿瘤或囊肿等。贝组替凡是一款HIF-2α（低氧诱导因子2α）抑制剂；HIF-2α在多种肿瘤类型中高表达，可在低氧状态下促进肿瘤细胞的增殖与存活。 贝组替凡治疗VHL病相关肿瘤适应证获得EC批准主要基于LITESPARK-004研究的积极数据，该研究中，贝组替凡治疗的VHL病相关RCC、CNS血管母细胞瘤以及pNET患者ORR分别达到49%、63%和83%，中位DOR均未达到。 贝组替凡治疗PD-1/PD-L1抑制剂和VEGF靶向药物经治RCC获得EC批准主要基于LITESPARK-005研究的积极数据。在该研究中，贝组替凡治疗将患者疾病进展或死亡的风险降低了25%，ORR显著高于依维莫司治疗（22% vs 4%）。 ->点击文末阅读原文，解锁完整双语新闻 企业动态 No.1 / 晶泰科技与恒健控股公司共同启动大湾区AI+创新联合体项目 2025年2月19日，晶泰科技（2228.HK）与广东恒健投资控股有限公司计划共同择址启动大湾区“人工智能+”科技与产业融合创新联合体项目。该项目旨在响应国家 “创新联合体” 战略，依托 “AI+机器人自动化” 技术，联合多方资本资源与产业链上下游先进企业，构建全球领先的研发创新基础设施与产业孵化生态系统，促进战略性产业集群化发展，引领 AI 医药、新材料、新能源、机器人等产业的未来发展。 根据项目规划的方向，项目相关参与方计划在未来10年内，共同引导带动投入数十亿的投资规模，建设创新联合体的物理载体和公共实验室，逐步打造大湾区人工智能算法算力和规模化机器人集群的人工智能研发基础设施。 ->点击文末阅读原文，解锁完整双语新闻 No.2 / 渤健斥资5.5亿美元获得Stoke罕见病新药Zorevunersen授权 2025年2月18日，渤健（Biogen，NASDAQ：BIIB）宣布与Stoke Therapeutics达成合作。双方将合作开发和商业化Zorevunersen，这是一款拟用于Dravet综合征的创新疗法。 Dravet综合征是一种罕见的遗传性癫痫，与难治性癫痫发作及神经发育障碍有关。Zorevunersen是一种反义寡核苷酸（ASO）药物，靶向SCN1A基因，该基因是大多数Dravet综合征患者的根本病因。Stoke Therapeutics近期已与美国、欧洲和日本监管机构沟通，计划于2025年第二季度启动Zorevunersen的全球III期注册研究（EMPEROR）；该研究的关键数据预计于2027年下半年公布，将支持Zorevunersen在全球监管申请。 根据合作条款，Stoke Therapeutics将继续领导Zorevunersen的全球开发工作，并保留Zorevunersen在美国、加拿大和墨西哥的独家开发和商业化权利。渤健获得Zorevunersen在全球其他地区的独家商业化权利。交易完成后，Stoke Therapeutics将获得1.65亿美元的首付款。双方将按比例分担Zorevunersen的外部临床开发成本（渤健30%，Stoke Therapeutics 70%）。此外，Stoke Therapeutics还将有资格获得高达3.85亿美元的开发和商业化里程碑付款，以及基于渤健潜在净销售额的分成。 ->点击文末阅读原文，解锁完整双语新闻 No.3 / 12.4亿美元！Radiance获石药集团ROR1抗体SYS 6005海外权益 2025年2月19日，石药集团（1093.HK）发布公告称，公司与Radiance Biopharma达成合作，授予后者SYS 6005在美国、欧盟、英国、瑞士、挪威、冰岛、列支敦士登、阿尔巴尼亚、黑山、北马其顿、塞尔维亚、澳大利亚和加拿大的开发及商业化独家权益。 根据协议条款，石药集团将获得1500万美元首付款，最高1.5亿美元潜在开发和里程碑付款，以及最高10.75亿美元潜在销售里程碑付款，并收取根据该产品于该地区的年度销售净额计算的分层销售提成。 SYS6005是重组抗人类受体酪氨酸激酶样孤儿受体1（ROR1）抗体，利用本集团专有的酶催化定点抗体偶联技术，能将有效的有丝分裂抑制剂MMAE靶向性地导向ROR1表达的癌细胞，而其连接符的稳定性有助于将高浓度的MMAE送达肿瘤中，并同时通过减少不良的全身暴露量而将副作用减低。与正常组织相比，ROR1在多种血液恶性肿瘤及实体肿瘤中高度表达，其表达与疾病进展及治疗反应密切相关。 ->点击文末阅读原文，解锁完整双语新闻 No.4 / 美敦力FY2025Q3财报：营收增长4.1%至83亿美元 2025年2月18日，医疗器械巨头美敦力（NYSE：MDT）公布了2025财年（FY25）第三季度（Q3，截至2025年1月24日）的财务业绩。 美敦力FY25Q3全球营收达到83亿美元，有机增长（下同）4.1%。其中，心脏消融解决方案业务因脉冲电场消融（PFA）产品的强劲表现，营收增长超20%。按业务划分，心血管产品组合营收30.37亿美元（+5.0%），神经科学产品组合营收24.58亿美元（+5.2%），医疗外科产品组合营收20.72亿美元（-0.4%），糖尿病业务营收6.94亿美元（+10.4%）。 美敦力在报告中重申，FY25营收有机增长预期将在4.75%至5%的范围内。 ->点击文末阅读原文，解锁完整双语新闻 全球医疗情报领导者 解锁隐藏在数据中的商业潜力  关于 G B I ” 自从2002年成立以来，GBI始终以技术为驱动，为药企、器械及行业相关服务商提供贯穿生命周期的全球药品市场竞争数据、全球行业资讯、HCPs洞察、全国医疗器械数据等商业信息与洞察，助力企业在进行战略布局和决策时，脱颖而出。历经20余年的深耕细作GBI已成为95%以上跨国药企、国内头部药企、咨询与投资机构等医疗圈灯塔用户值得信赖的长期合作伙伴。 联系我们 投稿 | 发稿 | 媒体合作 ▶ xujingou@baidu.com 数据库 | 咨询服务 | 资讯追踪 ▶ 点击左下“阅读原文”完成表单填写 点击阅读原文，解锁完整双语新闻

WELIREG is the first and only oral hypoxia-inducible factor-2 alpha inhibitor approved in the European Union RAHWAY, NJ, USA I February 18, 2025 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Commission (EC) has conditionally approved WELIREG ® (belzutifan), Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, as monotherapy for: The EC approval of these two indications is based on results from the LITESPARK-004 and LITESPARK-005 trials, respectively, and follows the positive recommendation from the Committee for Medicinal Products for Human Use adopted in December 2024 . This marks the first approval for WELIREG in the European Union (EU). WELIREG is now approved in over 30 countries for certain adult patients with previously treated advanced RCC and in more than 40 countries for adult patients with certain eligible VHL disease-associated tumors. “The approval of WELIREG in the EU introduces the first and only systemic treatment option for adult patients with certain VHL disease-associated tumors for whom localized procedures are unsuitable, and offers a new option for adult patients with advanced clear cell renal cell carcinoma that progressed following a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “This is an important moment, and we are pleased that WELIREG, a first-in-class HIF-2α inhibitor, can now potentially help these patients in need.” This approval allows marketing of WELIREG for these indications in all 27 EU member states, as well as Iceland, Liechtenstein and Norway. The conditional approval of WELIREG will be valid for one year, subject to yearly renewal, pending additional clinical data from LITESPARK-004 and another ongoing Phase 2 trial of WELIREG in patients with certain VHL disease-associated tumors. Timing for commercial availability of WELIREG in individual EU countries will depend on multiple factors, including the completion of national reimbursement procedures. Results in Patients With Certain Eligible VHL Disease-associated Tumors (LITESPARK-004) WELIREG is now the first and only systemic therapy for the treatment of VHL disease-associated tumors in the EU. The approval in adult patients with certain eligible VHL disease-associated tumors is based on objective response rate (ORR) and duration of response (DOR) results from the LITESPARK-004 trial. WELIREG was approved in the U.S. in August 2021 for the treatment of adult patients with VHL disease who require therapy for associated RCC, CNS hemangioblastomas or pNET not requiring immediate surgery based on the results from LITESPARK-004. In patients with VHL disease-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62) (n=30/61); all responses were partial responses (PR). Median DOR for these patients was not reached, with ongoing responses ranging from 2.8+ to 22+ months; among responders, 56% (n=17/30) maintained a response for at least 12 months. Among these 61 patients, the study also evaluated response rates in other common disease-associated tumors including CNS hemangioblastomas and pNET. In patients with VHL disease-associated CNS hemangioblastomas (n=24) in this trial, WELIREG showed an ORR of 63% (95% CI, 41-81) (n=15/24), with a complete response (CR) rate of 4% (n=1/24) and a PR rate of 58% (n=14/24). Median DOR for these patients was not reached, with ongoing responses ranging from 3.7+ to 22+ months; among responders, 73% (n=11/15) maintained a response for at least 12 months. In patients with VHL disease-associated pNET (n=12) in this trial, WELIREG showed an ORR of 83% (95% CI, 52-98) (n=10/12), with a CR rate of 17% (n=2/12) and a PR rate of 67% (n=8/12). Median DOR for these patients was not reached, with ongoing responses ranging from 11+ to 19+ months; among responders, 50% (n=5/10) maintained a response for at least 12 months. Results in Certain Patients With Previously Treated Advanced RCC (LITESPARK-005) The approval in adult patients with advanced clear cell RCC that progressed following two or more lines of therapy, including a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies, is based on progression-free survival (PFS) and ORR results from the LITESPARK-005 trial, which was the first trial in advanced RCC to specifically evaluate patients who progressed following these treatments. WELIREG was approved in the U.S. in December 2023 for the treatment of adult patients with advanced RCC following both a PD-1 or PD-L1 inhibitor and a VEGF-tyrosine kinase inhibitor based on the results from LITESPARK-005. In the trial, WELIREG reduced the risk of disease progression or death by 25% (HR=0.75 [95% CI, 0.63-0.90]; p=0.0008) versus everolimus. Median PFS was 5.6 months (95% CI, 3.9-7.0) for WELIREG versus 5.6 months (95% CI, 4.8-5.8) for everolimus. The ORR for WELIREG was 22% (n=82) (95% CI, 18-27), with a CR rate of 3% (n=10) and a PR rate of 19% (n=72), and the ORR for everolimus was 4% (n=13) (95% CI, 2-6), with no patients achieving a CR and a PR rate of 4% (n=13). About LITESPARK-004 LITESPARK-004 is an open-label Phase 2 trial (ClinicalTrials.gov, NCT03401788 ) evaluating WELIREG for the treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received WELIREG (120 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint is ORR in VHL disease-associated RCC. Secondary endpoints include, DOR, time to response, PFS, time to surgery and safety. Additionally, this study evaluated response rates in other common VHL disease-associated tumors including pNET and CNS hemangioblastomas. About LITESPARK-005 LITESPARK-005 is an open-label, randomized, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT04195750 ) evaluating WELIREG compared to everolimus for the treatment of patients with unresectable, locally advanced or metastatic clear cell RCC that progressed following PD-1 or PD-L1 checkpoint inhibitor and VEGF receptor targeted therapies either in sequence or in combination. The trial enrolled 746 patients who were randomized to receive WELIREG (120 mg orally once daily) or everolimus (10 mg orally once daily). The dual primary endpoints are PFS and overall survival. Secondary endpoints include ORR, DOR and safety. About von Hippel-Lindau disease Von Hippel-Lindau disease is a rare genetic disease, which impacts an estimated 200,000 people worldwide and an estimated 10,000 to 15,000 people in Europe. Patients with VHL disease are at risk for recurrent, benign blood vessel tumors as well as some cancerous ones. One of the most commonly occurring tumors is RCC, a form of kidney cancer, which occurs in about 70% of patients with VHL disease. About renal cell carcinoma Renal cell carcinoma is by far the most common type of kidney cancer. Clear cell RCC is considered the most common form of RCC, representing about 70% of all cases. In 2020, more than 130,000 new cases of RCC were diagnosed in Europe. Renal cell carcinoma is about twice as common in men than in women. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage. About WELIREG ® (belzutifan) 40 mg tablets, for oral use Indications in the U.S. Certain von Hippel-Lindau (VHL) disease-associated tumors WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. Advanced Renal Cell Carcinoma (RCC) WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Selected Safety Information for WELIREG Warning: Embryo-Fetal Toxicity Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective. Anemia WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG. In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established. In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs. Hypoxia WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider. In LITESPARK-004, hypoxia occurred in 1.6% of patients. In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months). Embryo-Fetal Toxicity Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Adverse Reactions In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each). WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%). The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%). In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%). WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%). Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%). The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%). Drug Interactions Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended. Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding. Lactation Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose. Females and Males of Reproductive Potential WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG. Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown. Pediatric Use Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established. Merck’s focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/ . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck