TDT/SCD Lentiviral Therapy Boasts Quick, Well-Tolerated Engraftment in Patients


KL003 favorably compares to platelet and neutrophil recovery rates of approved gene therapies.

Most patients with transfusion-dependent β-thalassemia (TDT) treated with KL003 gene therapy became transfusion-independent with fast engraftment and without serious adverse events (AEs).

Data on KL003 from a single-dose, open-label study were presented at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting 2024, held May 7-10 in Baltimore, Maryland, by Zhen Gao, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, and Tianjin Institutes of Health Science, Tianjin, China.

“Clinical evaluation of autologous hematopoietic stem cell (HSC)-based gene therapies for β-thalassemia major patients have been well-advanced in the US and Europe but not in other parts of the world,” Gao and colleagues wrote in their poster.

KL003 is a lentiviral vector gene therapy that delivers a function β-globin gene and is intended to treat either TDT or sickle cell disease (SCD). The study reported data from 17 participants with TDT aged between 5 and 35 years. Participants had their HSCs mobilized with G-CSF and plexiform and collected by apheresis, received busulfan myeloablative conditioning, and then received reinfusion of the transduced HSCs.

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Gao and colleagues found that a cohort of 11 patients with less than 5,000 ug/L ferritin had a median engraftment time of 13 days for neutrophils (range, 8-15) and 19 days for platelets (range, 13-28). In comparison, the cohort of 6 patients with over 5,000 ug/L had a media engraftment time of 14.5 days for neutrophils (range, 9-18 days) and 39 days for platelets (range, 19-121; P = .0240). Altogether, neutrophil recovery had a median engraftment time of 14 days (range, 8-18) and platelet recovery of 21 days (range, 13-121).

In terms of efficacy, 16 of 17 participants (94%) achieved transfusion independence at a median of 18 days after treatment (range, 10-177), the longest period without transfusion continuing for 24 months so far as of the data cutoff date.

Gao and colleagues compared the efficacy measures to 2 FDA-approved gene therapies for SCD and TDT, exagamglogene autotemcel (Casgevy, Vertex) and lovotibeglogene autotemcel (bluebird bio), citing a 95% and 89% transfusion-independence (TI) rate and a 28.5-day (range, 12-345) and 25.2-day (range, 0-72) to TI time, respectively. They also compared the engraftment measures, citing a 29-day (range, 12-56) and 26-day (range, 13-39) neutrophil recovery and a 44-day (range, 20-213) and 46-day (range, 20-94) platelet recovery time, respectively.

The investigators also stated their optimized vector, vector production, and cell transduction processes increase usage and yield and therefore reduce high manufacturing costs all too common with gene therapies.

“Our clinical trial results demonstrate potentially curative outcomes of KL003 in β-thalassemia major patients, including those in poor clinical conditions (with severe iron overload), which account for the majority of the β-thalassemia major patients in developing countries,” Gao and colleagues wrote. “In addition, our optimized transduction process of HSCs might have contributed to maintaining stemness of HSCs, which is essential for quick engraftment but often gets lost during EX vivo manipulation. This has led to significantly faster engraftment and better efficacy without severe AEs. Thus, KL003 could provide a potential functional cure for β-thalassemia major patients.”

Gao Z, Huang J, Fang L, et al. Clinical Efficacy and Safety of Gene Therapy for Transfusion-Dependent β-Thalassemia Patients with Quick Engraftment of Genetically Modified Hematopoietic Stem Cells. Presented at: ASGCT Annual Meeting 2024, May 7-10; Baltimore, Maryland.
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