Table 1.
Gene therapy and genome editing clinical trials for TDT.
| Strategy | Modality | Sponsoring Agent | Clinical trial ID Status | Estimated participants | Results/notes |
|---|---|---|---|---|---|
| β-Like globin gene replacement | Lentiviral Vector (LVV) | ||||
| TNS9.3.55 LVV/βA |
Memorial Sloan Kettering Cancer Center (MSKCC) |
NCT01639690 Phase I |
10 | 4 participants followed for 90 months had stable engraftment. Transfusion requirements were reduced by 35-57% in 2 individuals. HSC transduction and LVV copy number were low. | |
| BB305 LVV/βA-T87Q |
bluebird bio |
NCT01745120 Phase I, II |
22 | Reduced or eliminated RBC transfusions in 22 patients with TDT without LVV-related severe adverse events. | |
| BB305 LVV/βA-T87Q |
bluebird bio |
NCT02151526 Phase I, II |
7 | 4 patients followed for a approximately 4.5 years became transfusion independent with reductions in dyserythropoiesis and iron overload. | |
| OTL-300 GLOBE LVV/βA |
IRCCS San Raffaele & Orchard Therapeutics |
NCT02453477 Phase I/II |
10 | Modified cell product administered into bone marrow. All three adults treated exhibited reduced transfusion requirements. Three of 4 evaluable pediatric patients became transfusion-independent. | |
| BB305 LVV/βA-T87Q |
bluebird bio |
NCT02906202 Northstar-2 Phase III |
23 | 23 individuals treated, including children (4-34 years old). 91% became transfusion-independent with median follow-up of 29.5 months. | |
| BB305 LVV/βA-T87Q |
bluebird bio |
NCT03207009 Northstar-3 Phase III |
18 | No results reported | |
| LVV/Undisclosed | Shenzhen Geno-Immune Medical Institute China |
NCT03351829 Phase I/II |
20 | No results reported | |
| LVV/βA | Nanfang Hospital of Southern Medical University China |
NCT03276455 Phase I/II |
10 | No results reported | |
| LVV/βA-T87Q | BGI-research & Shenzhen Children’s Hospital China |
NCT04592458 Phase I |
10 | No results reported | |
| LVV/βA-T87Q | Shanghai BDgene Co., Ltd |
NCT05015920 Phase I |
10 | No results reported | |
| HbF Induction | Nuclease/Target | ||||
| Cas9 disruption of BCL11A erythroid enhancer via NHEJ | CRISPR Therapeutics; Vertex Pharmaceuticals |
NCT03655678 Phase I, II, III |
45 | 42 of 44 pts stopped RBC transfusions; 2 pts had 75% and 89% reductions in RBC transfusions | |
| BCL11A -Targeted zinc finger disruption of BCL11A erythroid enhancer via NHEJ (ST-400) | Sangamo Therapeutics and Sanofi |
NCT03432364 Phase I, II |
6 | 5 patients had transient elevation of that was not sustained. No long-term therapeutic benefit due to low HSC transduction efficiency. | |
| Cpf1 NHEJ mediated disruption of BCL11A binding site (EDIT-301) | Editas Medicine Inc. |
NCT05444894 Phase I, II |
6 | No results reported | |
| Cas9 disruption of BCL11A erythroid enhancer (ET01) | Edigene & Institute of Hematology & Blood Disease Hospital, Tianjin. China. |
NCT04390971 Phase I |
8 | No results reported | |
| γ-Globin reactivation using Glycosylate Base Editors (exact mechanism not specified) | Bioray Laboratories. Shanghai, China |
NCT05442346. Phase I/II Clinical Trial |
5 | No results reported | |
| Cas9 disruption of BCL11A erythroid enhancer via NHEJ | Bioray Laboratories Shanghai China |
NCT04211480 Phase I, II |
12 | 2 children with TDT achieved transfusion independence with normal hemoglobin levels after f>18 months follow-up | |
Current clinical trials for TDT on ClinicalTrials.gov as of November 2022.
Abbreviations: HSC, hematopoietic stem cell; TDT, transfusion dependent β-thalassemia; NHEJ, non-homologous end joining; HDR, homology directed repair; LVV: Lentiviral vector; CRISPR, Clustered regularly interspaced short palindromic repeats, HbF, fetal hemoglobin.