Every diligent successful the survey was VOC-free astatine the clip of the information cut.
New probe suggests exagamglogene autotemcel is simply a viable attraction enactment for patients with terrible sickle compartment disease (SCD).
A team, led by Haydar Frangoul, MD, Sarah Cannon Center Research Institute and The Children’s Hospital astatine TriStar Centennial, reported the4 efficacy and information information from 31 patients with sickle compartment illness dosed with exa-cel.
The information was presented during the 2022 American Society of Hematology (ASH) Annual Meeting.
The Treatment
Elevated fetal hemoglobin is linked to improved outcomes for patients with sickle compartment disease. One imaginable attraction enactment is exagamglogene autotemcel, a compartment therapy aimed astatine reactivating HbF done non-viral, ex vivo CRISPR/Cas9 gene-editing astatine the erythroid enhancer portion of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).
In the CLIMB SCD-121 study, investigators recovered a azygous dose of exa-cel accrued HbF and full hemoglobin (Hb) eliminated vaso-occlusive crises (VOCs) successful patients with terrible sickle compartment illness aged 12-35 years. Each diligent had a past of astatine slightest 2 VOCs per twelvemonth successful the proceeding 2 years earlier screening
The investigators monitored exa-cel patients aft pharmacokinetic-adjusted, busulfan myeloablation and infusion for engraftment, full Hb, HbF, BCL11A-edited alleles, transfusions, VOCs, and adverse events.
The squad sought superior endpoints of the proportionality of patients who person not experienced a terrible VOC for astatine slightest 12 months aft the infusion of exa-cel, starting 60 days aft their past RBC transfusion.
Data Cut-Off
The astir caller information chopped was February 2022, wherever 31 patients with a median property of 22.5 years were infused with exa-cell for a mean follow-up of 9,6 months. Of this group, 19.4% (n = 6) were betwixt the ages of 12-17 and 93.5% (n = 29) had the βs/βs genotype.
Prior to screening, patients experienced an mean of 3.9 terrible VOCs per year, portion each patients engrafted neutrophils and platelets with a median clip of 27 and 32 days, respectively aft exa-cel infusion.
Every diligent successful the survey was VOC-free at the clip of the information chopped (duration of follow-up 2.0–32.3 months aft exa-cel infusion) with a median clip from exa-cel infusion to past RBC transfusion was 19 days.
The mean proportionality of HbF was >20% by period 3, with mean full Hb levels >11 g/dL connected and aft Month 3.
In addition, each 11 patients who person astatine slightest 12 months of follow-up aft exa-cel infusion person maintained HbF levels >20% portion experiencing nary VOCs.
At period 6, the mean proportion of edited BCL11A alleles successful bony marrow CD34+ HSPCs and peripheral humor mononuclear cells was 86.6% and 76.0%, respectively, which remained stable in each patients who had ≥1 twelvemonth of follow-up.
For safety, determination were nary patients who had superior adverse events deemed related to exa-cel, with nary deaths, discontinuations, oregon malignancies.
“Exa-cel infusion led to the elimination of VOCs successful each patients with SCD, with associated clinically meaningful increases successful HbF and full Hb that were maintained implicit time,” the authors wrote. “Proportions of CRISPR/Cas9-edited BCL11A alleles person remained unchangeable aft ≥1 year, indicating that semipermanent HSCs were successfully edited. The information illustration was mostly accordant with that of busulfan myeloablation and autologous transplant. Exa-cel has the imaginable to beryllium the archetypal CRISPR/Cas9-based therapy to supply a one-time functional cure for SCD.”
The study, “`Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Severe Sickle Cell Disease,” was published online by ASH 2022.
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