Table 1:
Gene therapy and genome editing clinical trials for SCD
| Strategy | Modality | Sponsoring Agent | Clinical trial ID Status | Estimated participants | Results |
|---|---|---|---|---|---|
| β-Like globin gene replacement | LentiViral Vector (LV) | ||||
| GLOBE1 anti-sickling β-globin (βAS3) LV | Assistance Publique–Hopitaux de Paris | NCT03964792 Phase I, II | 10 | No results posted | |
| Lenti/G-bAS3-FB anti-sickling β-globin (βAS3) LV | University of California, Los Angeles | NCT02247843 Phase I, II | 6 | No results posted | |
| LentiGlobin BB305 anti-sickling β-globin (βA-T87Q) LV | Bluebird bio | NCT02140554 Phase I, II | 50 | 25 SCD (group C) participants followed for 3–25 months. Most had near-pancellular expression of HbAT87Q ≥6 months after therapy with 99.5% mean reduction in the annualized VOC+ACS rate overall | |
| LentiGlobin BB305 anti-sickling β-globin (βAS3) LV | Bluebird bio | NCT04293185 Phase III | 35 | No results posted | |
| ARU-1801 γ-globin G16D LV) | Cincinnati Children’s Hospital Medical Center | NCT02186418 Phase I, II | 10 | 3 SCD patients, follow-up 9–30 months, with sustainable expression of HbF and clinical improvement | |
| BCH-BB694 anti-BCL11A shRNA LV | Boston Children’s Hospital | NCT03282656 Phase I, II | 10 | 6 SCD participants infused, follow-up 7–29. months. No patient has had a VOC, ACS, or stroke since the treatment. | |
| Nuclease/Target | |||||
| HbF Induction | Cas9 disruption of BCL11A erythroid enhancer via NHEJ | CRISPR Therapeutics; Vertex Pharmaceuticals Incorporated | NCT03745287 Phase I, II, III | 45 | 2 SCD participants with follow-up of 3 and 12 months have had no SCD-related VOCs since infusion of gene-modified cells; 5 β-thalassemia participants with follow-up of 3–15 months are transfusion independent. |
| BCL11A (BIVV003)-Targeted zinc finger disruption of BCL11A erythroid enhancer via NHEJ (PRECIZN-1) | Bioverativ, a Sanofi company | NCT03653247 Phase I, II | 8 | 4 of 4 treated participants showed higher Hb levels and elevated HbF expression with clinical improvement over 2 years follow up. 1 serious VOC in 1 patient approximately 9 months post therapy | |
| OTQ923/HIX763 Cas9 disruption of BCL11A erythroid enhancer via NHEJ or Cas9 disruption of BCL11A binding motif in γ-globin promoter via NHEJ | Novartis/Intellia | NCT04443907 Phase I, II | 30 | No results posted | |
| EDIT-301 Cpf1 disruption of BCL11A binding motif in γ-globin promoter via NHEJ | Editas Medicine, Inc. | NCT04853576 Phase I, II | 40 | No results posted | |
| HbS mutation repair | GPH101 Hb β6: GTG->GAG via Cas9 HDR | Graphite Bio | NCT04819841 Phase I, II | 15 | No results posted |
| CRISPR_SCD001 Hb β6: GTG->GAG via Cas9 HDR | UCSF Benioff Children’s Hospital Oakland | NCT04774536 Phase I, II | 9 | No resuits posted | |
All clinical trials for SCD listed on ClinicalTrials.gov as of April 2022 are shown. Some trials also include patients with β-thalassemia. ACS, acute chest syndrome; NHEJ, non-homologous end joining; HDR: homology directed repair; LV: Lentiviral vector; VOC, vaso-occlusive crisis; shRNA: short hairpin RNA, CRISPR: Clustered regularly insterspaced short palindromic repeats, HbF: fetal hemoglobin.