ALLO-647

摘要：Allogene Therapeutics 在其 CAR-T 疗法 cema-cel 治疗大 B 细胞淋巴瘤的 II 期 ALPHA3 试验中，因一名患者死亡且死因被认定与免疫抑制抗体 ALLO-647 相关，决定停用该抗体并调整试验方案。此次事件导致公司股价下跌 12%，也引发了行业对 CAR-T 疗法清淋方案选择的关注。一、试验突发死亡事件，矛头指向 ALLO-647 Allogene 的 II 期 ALPHA3 试验正聚焦于其 CAR-T 候选药物 cemacabtagene ansegedleucel（简称 cema-cel），该药物用于治疗大 B 细胞淋巴瘤。在试验中，ALLO-647 作为清淋疗法的一部分，用于为患者接受 cema-cel 治疗做准备。 然而，一名患者在接受输注 54 天后死亡。Allogene 在周五的新闻稿中指出，患者死因是 “免疫抑制状态下的播散性腺病毒感染” 引发的肝衰竭。公司强调，此类严重感染在其试验中 “罕见”，但一旦出现，部分与 ALLO-647 导致的免疫抑制相关。 William Blair 的分析师在给投资者的报告中也认同这一结论，认为现有证据支持该事件源于 ALLO-647 介导的 T 细胞长期抑制，而非 cema-cel 本身。二、Allogene 紧急调整：停用 ALLO-647，转向 FC 方案 鉴于患者死亡事件，Allogene 已决定终止 ALPHA3 试验中使用 ALLO-647 的试验组，并将该抗体从研发管线中彻底移除。 此后，公司将仅采用氟达拉滨与环磷酰胺（FC 方案）作为 cema-cel 治疗的清淋疗法。同时，Allogene 计划在 2026 年上半年对 ALPHA3 试验进行无效性分析，以评估调整后方案的进展。三、市场与分析师的双重反应 市场对这一决定迅速做出回应，Allogene 股价在周五交易中下跌 12%。 分析师团队虽支持公司停用 ALLO-647 的决定，但也提出担忧：标准 FC 清淋方案可能无法像联合 ALLO-647 时那样，让 cema-cel 实现 “强劲的扩增与持久存在”。不过他们也指出，ALPHA3 试验入组患者的疾病负担较低，“可能无需强化清淋方案”；且若 cema-cel 获批，仅用 FC 方案或因安全性风险更低，带来 “更高的商业接受度”。四、CAR-T 研发再思：平衡疗效与安全 此次事件再次凸显了 CAR-T 疗法研发中清淋方案选择的复杂性。清淋疗法的核心是为 CAR-T 细胞 “扫清障碍”，帮助其在体内扩增，但过度免疫抑制可能增加感染风险。 Allogene 的调整意味着其需在 cema-cel 的疗效与患者安全间寻找新平衡点。行业也在关注，这一调整是否会影响 cema-cel 的研发进度，以及 FC 方案能否在保证安全性的同时，支撑药物达到预期疗效。 对于 Allogene 而言，2026 年上半年的无效性分析将成为评估这一调整成败的关键节点。 参考来源：https://www.biospace.com/drug-development/allogene-scraps-immunosuppressive-antibody-after-patient-death-in-lymphoma-trial 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

iStock, Andrii Yalanskyi While the deaths occurred in patients who had been treated with Agios’ anemia treatment Pyrukynd, the biotech insisted in an SEC filing midday Monday that the drug’s risk-benefit pro unchanged. Shares of Massachusetts-based Agios Pharmaceuticals were put through the wringer on Monday after the FDA’s Adverse Event Reporting System revealed four deaths in patients who had taken its anemia drug Pyrukynd. Leerink analysts flagged a 23% dip at the stock’s lowest point, with share prices hitting $26.75 at market opening Monday before rebounding to $36.16 by the closing bell, a 3% increase from its closing price last Friday. In pre-market trading Tuesday, Agios shares have dipped 2% Agios filed an SEC document on Monday to address the four deaths, which were first made public by a securities analyst who filed a Freedom of Information Act request to the FDA’s safety database, to which Agios had reported these deaths. In its regulatory filing, Agios reassured investors that the deaths have “not altered the established benefit-risk profile” for Pyrukynd. Two of the deaths were in older patients: one in a 61-year-old man and another in a 93-year-old woman, both of whom were being treated for pyruvate kinase (PK) deficiency. Agios reported these cases to the FAERS on June 28, 2024 and July 17, 2025, respectively, according to the Leerink analysts. The last two fatalities were in much younger women, a 28-year-old and a 26-year-old, who had sickle cell disease and were being treated with Pyrukynd under compassionate use. The latter of these two cases was reported to the FDA on July 15 this year. Leerink said that these latter two deaths are “concerning given the young age of the patients.” But after following up with Agios, the analysts learned that these two younger patients were actually the same person. “The 28-year-old patient was actually a duplicate of the 26-year-old patient which was incorrectly entered into the database,” the Leerink note read, adding that this has in turn “largely offsets our concerns” that these deaths represent “a heightened mortality risk of Pyrukynd.” Despite Agios’ clarifications, “it is difficult to fully dismiss the impact of the safety concerns” on an upcoming PDUFA data for Pyrukynd, Leerink added. Agios is proposing Pyrukynd for the treatment of patients with alpha- or beta-thalassemia regardless of their dependence on transfusions. The FDA is expected to release its verdict on Sept. 7 . The drug was first approved in 2022 for adults with hemolytic anemia with PK deficiency. Patient deaths have been in the news in recent months, the most visible of which have been the three mortalities linked to Sarepta’s gene therapy portfolio: two to its Duchenne muscular dystrophy product Elevidys and one to an investigational limb-girdle muscular dystrophy candidate. Then, late last week, Allogene Therapeutics likewise reported a patient death in a Phase II study of its CAR T therapy cemacabtagene ansegedleucel, though the fatality was ultimately linked to ALLO-647, an anti-CD52 antibody used as an immunosuppressive treatment to prepare patients for the cell therapy.