Analysis Finds Preinfusion Factors that Predict Lovo-Cel Efficacy in SCD

By Patrick Daly - Last Updated: February 26, 2024

Reduction of hemolysis was significantly correlated with postinfusion transduction efficacy in patients with sickle cell disease (SCD) treated with lovotibeglogene autotemcel (lovo-cel) from the HGB-206 and HGB-210 clinical trials, according to a presented at the 2024 Tandem Transplant & Cellular Therapy Meetings of ASTCT® and CIBMTR®.

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Transduction efficiency, evaluated via peripheral blood (PB) vector copy number (VCN), “is an important predictor of biologic efficacy and correlates with lovo-cel [drug product] attributes,” stated presenting author, Melissa Kinney, PhD, and fellow researchers at bluebird bio, Inc., in Somerville, Massachusetts.

Preinfusion Lovo-Cel Vector Copy Number Predicts Postinfusion Outcomes

The analysis included 47 patients with SCD from HGB-210 or group C of HGB-206 who received a single infusion of lovo-cel by February 13, 2023. A multivariate analysis was used to identify associations between transduction efficacy measures and hematological or hemolytic measures, and then a cross-validated random forest regression model based on 15 drug product attributes was used to identify factors that predicted PB VCN.

The analysis found an inverse correlation between PB VCN and hemoglobin (Hb)AT87Q levels and reticulocyte count, bilirubin levels, and erythropoietin — measures of transduction efficiency and hemolysis, respectively.

“This indicates that a higher proportion of transduced cells is associated with an increased resolution of sickle cell–associated hemolysis,” wrote Dr. Kinney and colleagues.

An assay that evaluates the propensity of sickling in red blood cells also showed a significant correlation with total hemoglobin after lovo-cel treatment. The authors expanded the regression model and further found that lovo-cel VCN in the myeloid lineage was the greatest preinfusion factor for predicting PB VCN.

Overall, “attributes of DP transduction efficiency as well as the resulting PB VCN predict successful treatment outcomes with lovo-cel,” concluded the study’s authors.

Related: What Are the Factors That Influence Response to Canakinumab Therapy?

 

Reference

Kinney MA, Shestopalov I, Christiansen L, et al. Abstract #302. Predictors of biologic efficacy with lovotibeglogene autotemcel (lovo-cel) gene therapy in patients with sickle cell disease. Presented at the 2024 Tandem Transplant & Cellular Therapy Meetings of ASTCT® and CIBMTR®. February 21-24, 2024; San Antonio, Texas.

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