Atidarsagene Autotemcel

同写意年度巨献！！本次大会特设“基因治疗”分会，7月24-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！“是医保限制了我们的想象力”。7月，当我国首个获批的腺相关病毒（AAV）基因治疗药物波哌达可基注射液的价格公布时，“同写意CGT天团”微信群中，一位医药公司创始人如是调侃。2025年4月，我国生物医药领域迎来里程碑事件——信念医药研发的波哌达可基注射液（商品名：信玖凝）正式获批上市。波哌达可基注射液针对中重度血友病B成年患者群体设计。作为一种因凝血因子Ⅸ（FIX）缺乏导致的遗传性出血疾病，血友病B患者终生面临反复出血风险，关节损伤与致残率高居不下。传统治疗要求患者终身定期输注凝血因子Ⅸ，且需每周多次静脉注射，沉重的治疗负担如影随形。如今，这款承载患者希望的治疗药物价格终于得到“官宣”——单瓶定价9.3万元。根据说明书，每位患者治疗的具体用药量（即瓶数）按照患者体重计算，例如70kg体重的处方用量是44瓶。早在波哌达可基注射液获批时，“同写意CGT天团”微信群中，就有60位医药公司创始人、高管参与了“定价竞猜”。普遍的猜想价格都在100万元左右，仅有4位“群友”猜想价格达到200万元。对于新药企业，超出预计的高定价固然值得欢呼，但尚未与高定价匹配的支付模式势必也会极大地限制患者可及。TONACEA01贵吗？波哌达可基注射液采用工程化改造的嗜肝性重组腺相关病毒（rAAV）载体，通过静脉注射将优化后的人凝血因子Ⅸ基因递送至患者肝脏细胞，利用宿主细胞转录系统持续表达凝血因子Ⅸ并分泌入血，从而恢复凝血功能。Ⅲ期临床试验数据显示，输注后52周患者平均FIX活性稳定在55.08 IU/dL（正常水平50-150 IU/dL），年化出血率均值降至0.6，凝血因子输注次数从每年58.2次降至2.9次，80.8%的患者实现零出血事件。在长达4.5年的随访中，9例受试者持续维持有效凝血功能，部分患者甚至完全脱离辅助止血治疗。安全性方面，未观察到严重血栓事件或抑制物生成，主要不良事件局限于短暂转氨酶升高，经糖皮质激素干预后均可控。在定价方面，国产波哌达可基注射液采用了单瓶定价9.3万元，药量依据患者体重计算的方式。为使更多血友病B患者尽快享受到基因治疗的创新成果，北京病痛挑战公益基金会在今年发起并运行血友病慈善援助项目。针对符合申请条件且审核通过后成功入组的血友病B患者，根据医嘱进行单次治疗过程中，只需自费购买30瓶药品，高于30瓶以上的治疗药物，将由此公益项目免费援助支持。也就是说，患者自付的治疗费用最高不会超过279万元。此外，信念医药与合作伙伴武田正在积极协同多方力量探索通过多元支付、疗效保险等模式，进一步改善患者可及。信念医药董事长肖啸表示，最理想的首先是医保按疗效分期付款，其次是一次性分担现有血友病药物每年报销30万封顶的费用。他还预期，“实际上患者最后支付的价格应该会低于200万元”。TONACEA02走向“可及”虽然波哌达可基注射液与上述CAR-T疗法相比贵了两倍有余，但深入分析可见，不同疗法的价值逻辑存在本质差异。CAR-T疗法主要针对复发难治性血液肿瘤，其疗效可能随时间衰减或需二次治疗；而基因疗法追求的是单次治疗长期缓解，现有数据已证实其持续获益超过5年。从经济学视角看，按传统治疗年均40万元费用计算，7年累积支出即与基因疗法相当，而患者预期获益期可达数十年。更关键的是，基因疗法采用通用型制剂路线，相较于个体化定制的CAR-T产品，其规模化生产具备显著的降本潜力。放眼全球基因治疗市场，高价是这一领域的普遍特征。截至2025年，美国已批准超过10款基因疗法，多数定价超过千万人民币。例如Orchard公司的Lenmeldy用于治疗异染性脑白质退化症，定价高达425万美元（约3040万人民币）；CSL Behring公司的Hemgenix同样用于治疗血友病B，定价350万美元（约2500万人民币）；蓝鸟生物的Zynteglo用于β-地中海贫血，定价280万美元（约2000万人民币）。相比之下，波哌达可基注射液279万元人民币的价格仅为美国同类产品Hemgenix的约11%。需要指出的是，许多罕见病药物在中国的售价已经是全球最低。创新药研发并非计算机领域的技术迭代，Deepseek的研发成本可以降至ChatGPT的十分之一，但若把这个比例放到创新药研发上，行业则将面临巨大挑战。可喜的是，我国支付创新机制正在同步破冰。同样是在7月，国家医保局公开了基本医保目录及商保创新药目录调整工作方案和申报指南的征求意见稿。2025年基本目录调整和商保创新药目录制定同步进行，并将通过价格协商的方式，综合专家和企业的意见，将协商成功的药品纳入商保创新药目录。随着更多本土创新药企加入竞争，越来越多的创新药进入国内市场，势必会推动更多元的支付和商业化模式，基因疗法从“天价”走向“可及”的路径日渐清晰。波哌达可基注射液的上市犹如投入湖面的石子，激荡起整个产业链的涟漪。从血友病B出发，中国基因治疗产业正在完成从单点突破到生态构建的跃迁。参考文章：1.https://m.21jingji.com/article/20250719/herald/c4884dffb553a450446cfe95ae77632e.html?t=9755762.https://mp.weixin.qq.com/s/aW3Dm4ewoMm7w48vTma2NA

AstraZeneca’s entry into the in vivo CAR-T space was sparked by initial data from a single patient, presented by EsoBiotec at January’s J.P. Morgan Healthcare Conference. \n Months after announcing an M&A deal with AstraZeneca, EsoBiotec has released the first small slice of data on the cell therapy asset that attracted the Big Pharma’s attention. Four patients with multiple myeloma who received the Belgian biotech’s in vivo T-cell editing therapy all responded to treatment, with the cancer of two patients resolving completely.The results come from EsoBiotec’s ongoing phase 1 trial in Wuhan, China, and were published in The Lancet on July 2. The trial aims to enroll up to 24 patients with relapsed or refractory multiple myeloma, a blood cancer that arises in plasma cells in the bone marrow. The four patients detailed in the paper had all been previously given at least two other treatments.EsoBiotec uses lentivirus vectors to deliver mRNA to T cells within the body, which is meant to endow the immune cells with the tools they need to pursue and destroy cancer cells. The company’s lead and only clinical asset, ESO-T01, is designed to reprogram T cells to target B-cell maturation antigen (BCMA), which is often overexpressed by malignant blood cells in multiple myeloma.All four patients were given a single infusion of ESO-T01 and had adverse events of varying severity, the trial researchers reported in the paper. All developed acute inflammatory reactions on the day of the infusion such as chills and fevers, and three patients developed low blood pressure that required medication. All the patients ultimately developed cytokine release syndrome, three at grade 3 and one at grade 1, and the patient with the most cancerous tissue also developed grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS).Other side effects included blood toxicities like neutropenia, leukopenia and thrombocytopenia, as well as lung infections.One patient’s cancerous lesions and malignant blood cells in the bone marrow disappeared completely by day 28 after infusion, and another’s disappeared by two months after treatment. The other two patients had partial responses, with lesions shrinking and cancer cells reduced.“In this case series, ESO-T01 appeared to eradicate extramedullary disease,” the authors wrote, referring to myeloma that has spread outside of the bone marrow. “Nevertheless, a larger cohort and longer follow-up are needed to further look into the persistence of in vivo-produced CAR T cells and their efficacy, and a randomized controlled design is required for more convincing results.” AstraZeneca’s $1 billion entry into the in vivo CAR-T space was sparked by initial data from a single patient, presented by EsoBiotec at January’s J.P. Morgan Healthcare Conference. The total cost for the British pharma to acquire EsoBiotec is split between an upfront payment of $425 million and up to $575 million in developmental and regulatory milestones.Lentiviral vectors like those used by EsoBiotec have sparked interest for their low toxicity and ability to infect both dividing and nondividing cells. Orchard Therapeutics’ approved metachromatic leukodystrophy therapy Libmeldy uses the vectors, as does Zynteglo, bluebird bio’s sickle cell treatment.