Table 5:
Overview of ongoing gene editing studies
| Modality (drug name) | Lead group (study name) | Status | Clinical trial number | Results | |
|---|---|---|---|---|---|
|
| |||||
| HbF induction | Cas9-mediated NHEJ; disruption of erythroid-specific enhancer in BCL11A gene (CTX001 or Exagamglogene autotemcel) | Vertex Pharmaceuticals/CRISPR Therapeutics (CLIMB SCD 121 Study) | Phase 1/2/3 (study closed to accrual, licensing application pending) | NCT03745287 and NCT05329649 | 31 patients with sickle cell disease (median age 23 years [range 12–34]) infused; all patients were VOC-free with a median duration of follow-up 9·6 months (range 2·0–32·3) after infusion |
| HbF induction | Cas9-mediated NHEJ, disruption of a regulatory element in the HBG1 and HBG2 promoters (OTQ923) | Novartis Pharmaceuticals | Phase 1/2 | NCT04443907 | Two patients with sickle cell disease (aged 22 and 21 years) infused; both patients were VOC-free with a follow-up of 6 and 12 months after infusion |
| HbF induction | ZFN-mediated NHEJ; disruption of erythroid-specific enhancer in BCL11A gene (BIVV003) | Sangamo Therapeutics (PRECIZN-1 Study) | Phase 1/2 | NCT03653247 | Four adult patients with sickle cell disease infused; all patients were VOC-free with a follow-up of 13–65 weeks after infusion |
| HbF induction | Cas12a (Cpf1)-mediated editing of the HBG1 and HBG2 promoters (EDIT-301) | Editas Medicine (RUBY Trial) | Phase 1/2 | NCT04853576 | No clinical trial results posted yet |
| HbF induction | Base editing of the HBG1 and HBG2 promoters (BEAM-101) | Beam Therapeutics (BEACON Trial) | Phase 1/2 | NCT05456880 | No clinical trial results posted yet |
| Correction of sickle mutation | Cas9-mediated HDR (CRISPR_SCD001) | UCSF Benioff Children’s Hospital, Oakland; University of California, Los Angeles; University of California, Berkeley | Phase 1/2 | NCT04774536 | No clinical trial results posted yet |
| Correction of sickle mutation | Cas9-mediated HDR (GPH101 or nulabeglogene autogedtemcel) | Graphite Bio (CEDAR Trial) | Phase 1/2 (study paused) | NCT04819841 | No clinical trial results posted yet; trial paused due to serious adverse event in first patient |
Data in the table updated as of Jan 11, 2023, from ClinicalTrials.gov. HDR=homology directed repair. NHEJ=non-homologous end joining. VOC=vaso-occlusive crisis.