地中海贫血基因治疗研究进展及思考
高欣洁, 刘艳, 王大威

Research progress and considerations for thalassemia gene therapy
GAO Xinjie, LIU Yan, WANG Dawei
表1 β-地中海贫血基因治疗的临床试验
Tab 1 Clinical trials of β-thalassemia gene therapy
Drug productSponsor

Status and

clinical trial identifier

Participant/nClinical trial result
Lentivirus-mediated β-globin gene addition
ZyntegloBluebird Bio

Phase Ⅰ/Ⅱ,

NCT01745120

22Transfusion independence (TI) occurred in 12 patients with non-β00 genotype and 3 patients with β00 genotype or IVS1-110 homozygous mutation[12]

Phase Ⅲ,

NCT02906202

24TI occurred in 20 patients with non-β00 genotype while the average Hb level was 117 g/L, and the median level of HbAT87Q was 87 g/L at the 12th month after infusion[13]

Phase Ⅲ,

NCT03207009

19One patient with β00 genotype had TI for ≥ 12 months, while the Hb level of 3 patients with TI for ≥ 6 months was up to 105136 g/L (HbAT87Q accounting for 95126 g/L)[3]
OTL-300Orchard TherapeuticsPhase Ⅰ/Ⅱ, NCT0245347710TI occurred in 3 pediatric patients, and red-cell transfusions were reduced in 4 patients[11]
HGI-001Hemu Gene Co., Ltd.

IIT,

NCT05745532

10The average Hb level of 5 patients was > 90 g/L during TI ≥ 12 months, with the median Hb level of 105 g/L at the most recent follow-up[14]
BD211BDgene Co., Ltd.

IIT,

NCT05015920

10Two patients with β00 genotype had TI for 25.5 months in average, with red blood cell lifespan being extended to more than 42 d[15]
KL003Kanglin Biotechnology

IIT,

ChiCTR2200055565

11The average neutrophil and platelet engraftment times were both 14 d. TI occurred in all patients, with the longest duration lasting 18 months[16]
GMCN508BGenmedicn BiopharmaIIT, NCT057625105Two patients with TDT had TI, including a 10-year-old pediatric patient with β0+ genotype
Gene editing to re-activate the expression of HbF
ST-400Sangamo TherapeuticsPhase Ⅰ/Ⅱ, NCT034323646The low transduction efficiency of HSCs resulted in no long-term therapeutic effect[17]
CTX001Vertex Pharmaceuticals

Phase Ⅲ,

NCT03655678

59The median duration of TI among 48 patients was 22.5 months, with a total Hb level of 131 g/L and HbF level of 119 g/L in average[4]
EDIT-301Editas Medicine

Phase Ⅰ/Ⅱ,

NCT05444894

9TI occurred in 7 patients, including 6 with follow-up ≥ 6 months, whose total Hb and HbF levels were 121 g/L and 109 g/L, respectively[18]
ET-01EdiGene Inc.IIT, NCT043909713One patient (β0+) had TI for>15 months, with a total Hb level of 110 g/L at the 18th month[19]
BRL-101BRL Medicine

Phase Ⅰ,

NCT05577312

10TI > 22 months occurred in all patients, including 5 with β00 genotype. The highest HbF level reached 140 g/L, with HbF-cells accounting for 98%99%[20]
RM-001Reforgene Medicine

Phase Ⅰ,

ChiCTR2300069244

12Twelve patients in Phase Ⅰ and 7 patients in IIT study had TI for> 6 months (including 13 with β00 genotype). Thirteen patients with ≥12 months of follow-up had an average HbF level of 117 g/L[21]
CS-101CorrectSequence TherapeuticsIIT, NCT062919618The first patient (β0+) had TI with HbF > 95 g/L at the 8th week