Kamau 干细胞疗法 nula-cel 获 FDA 先进疗法认定：3名镰状细胞病患者全部脱离输血
美国加利福尼亚州 South San Francisco 的 Kamau Therapeutics 11月12日宣布，美国食品药品监管局 FDA 已授予其在研干细胞疗法 nula-cel 再生医学先进疗法（RMAT）认定，用于治疗镰状细胞病。认定依据是正在进行的 1/2 期 RESTORE 试验的初步临床证据，nula-cel 此前已获得 FDA 的快速通道与孤儿药认定。
RESTORE 试验中，采用优化后生产工艺治疗的 3 名患者全部实现脱离输血，且没有发生血管闭塞事件。随访超过 6 个月的 2 名患者，镰状血红蛋白降至 20% 以下，低于防卒中目标的 30% 门槛，血红蛋白构成以成人型为主。
RMAT 认定授予初步临床证据显示有潜力满足严重疾病未被满足医疗需求的再生医学疗法，获认定疗法可获得与 FDA 更早、更频繁的沟通，并可能有资格获得优先审评与加速批准。
Kamau 首席执行官 Vali Barsan 表示，疼痛危象之外，镰状细胞在间期仍持续损伤身体，指南要求以置换输血把镰状血红蛋白维持在 30% 以下以防卒中，nula-cel 的设计目标是以一次性治疗纠正镰状细胞病的根本病因。首席医疗官 Jacob Garcia 表示，公司计划申请 FDA 建议的综合多学科 RMAT 会议，就形成注册性数据集的路径达成一致，包括优先审评的可能性与加速批准的终点，并计划在今年晚些时候公布 RESTORE 的更多中期疗效数据。
Nula-cel 是一种在研的镰状细胞病干细胞疗法，其做法不是诱导胎儿血红蛋白来代偿，而是直接把镰状突变纠正回正常的成人 β-珠蛋白序列：公司在体外以同源定向修复（HDR）精确编辑患者自身的长寿干细胞，在回输前逐批核验细胞产品的质量、身份、效能与安全性。这类细胞能够自我更新，一次治疗的设计目标是带来持久、可能终身的获益。该试验在 ClinicalTrials.gov 的登记号为 NCT04819841。
镰状细胞病是一种遗传性血液病，美国约有 10 万人患病，全球有数百万人。β-珠蛋白基因的单个突变产生镰状血红蛋白，使红细胞变硬，引发慢性溶血。疼痛危象是看得见的负担，卒中以及肾脏、视网膜与骨骼损伤则在间期悄悄累积，使美国患者的预期寿命缩短数十年。
需要说明的是，nula-cel 仍是在研疗法，尚未获批上市，RMAT 认定不等于批准，其疗效与安全性仍需更大规模试验确认。（来源：Kamau Therapeutics）
Kamau Stem Cell Therapy Nula-cel Wins FDA Advanced Therapy Designation: All 3 Sickle Cell Patients Transfusion-Free
Kamau Therapeutics of South San Francisco, California, announced on November 12 that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to nula-cel, its investigational stem cell medicine for sickle cell disease. The designation is based on preliminary clinical evidence from the ongoing Phase 1/2 RESTORE trial, and nula-cel also holds FDA Fast Track and Orphan Drug designations.
In RESTORE, all three patients treated with the optimized manufacturing process achieved transfusion independence with no vaso-occlusive events. The two patients with more than six months of follow-up have sickle hemoglobin below 20%, under the 30% threshold targeted for stroke prevention, with a predominantly adult hemoglobin profile.
RMAT designation is granted when preliminary clinical evidence indicates that a regenerative medicine therapy has the potential to address unmet medical needs in a serious condition. Designated therapies receive early, frequent FDA engagement and may be eligible for priority review and accelerated approval.
Kamau Chief Executive Officer Vali Barsan said pain crises matter, but between them sickled cells continue damaging the body, which is why guidelines call for exchange transfusions to keep sickle hemoglobin below 30% to prevent stroke, and that nula-cel was designed to correct the root cause of sickle cell disease in a single treatment. Chief Medical Officer Jacob Garcia said the company plans to request the comprehensive multidisciplinary RMAT meeting the agency recommended, to align on the path to a registrational dataset including the potential for priority review and endpoints for accelerated approval, and expects to share additional interim efficacy data from RESTORE later this year.
Nula-cel is an investigational stem cell medicine for sickle cell disease. Rather than inducing fetal hemoglobin to compensate for the disease, it is designed to correct the sickle mutation itself, converting it to the normal adult beta-globin sequence. Using ex vivo homology-directed repair (HDR), Kamau engineers a patient's own long-lived stem cells outside the body, verifying each cell product's quality, identity, potency and safety before it is returned to the patient. As these cells self-renew, a one-time treatment is designed to deliver durable, potentially lifelong benefit. The RESTORE trial is registered as NCT04819841.
Sickle cell disease is an inherited blood disorder affecting approximately 100,000 people in the United States and millions globally. A single mutation in the beta-globin gene produces sickle hemoglobin, which stiffens red cells and drives chronic hemolysis. Pain crises are the visible burden, while chronic organ damage, including stroke and injury to the kidneys, retinas and bones, accumulates silently between them, shortening U.S. life expectancy by decades.
Nula-cel remains investigational and is not approved; RMAT designation is not an approval, and its efficacy and safety must still be confirmed in larger trials. (Source: Kamau Therapeutics)
来源：Kamau Therapeutics
发布：GSM·美国（发布链接）
图片来源：图：镰状细胞病患者血涂片，可见镰刀形红细胞。Prof. Osaro Erhabor 摄，Wikimedia Commons，CC0。 / Image: Blood film in sickle cell disease showing sickle-shaped red cells. By Prof. Osaro Erhabor, via Wikimedia Commons, CC0.
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