DocWire NewsExa-Cel Eliminates Transfusions in Patients with Thalassemia

Pioneering CRISPR/Cas9-Based Therapy Marks a Paradigm Shift in β-Thalassemia Treatment

In a landmark study presented at the 2024 Tandem Transplant & Cellular Therapy Meetings, exagamglogene autotemcel (exa-cel) showcased its potential as a groundbreaking therapy in treating transfusion-dependent β-thalassemia, achieving significant success in eliminating the need for red blood cell transfusions. This advance not only signifies a leap in genetic editing therapies but also hints at broader implications for hematological conditions treatment.

Key Points:

• Exa-cel demonstrated a remarkable efficacy in eliminating red blood cell (RBC) transfusions in 95.5% of patients with transfusion-dependent β-thalassemia in the CLIMB THAL-111 trial.
• The therapy led to clinically significant increases in fetal hemoglobin (HbF) and total hemoglobin (Hb) levels, with patients achieving and maintaining Hb levels greater than 9.0 g/dL.
• The primary endpoint was the maintenance of a weighted average Hb ≥9.0 g/dL without RBC transfusion for over 12 months post-exa-cel infusion.
• Out of 44 patients aged 12-35 years, 42 successfully discontinued RBC transfusions after a median follow-up of 12.3 months.
• The treatment resulted in a stable proportion of edited BCL11A alleles in key hematopoietic cells, indicating successful and enduring genome editing.
• Two patients experienced serious adverse events, highlighting the need for monitoring but confirming a safety profile consistent with existing treatment modalities.
• Exa-cel’s impact suggests a potential one-time functional cure for patients with transfusion-dependent β-thalassemia, marking a significant step forward in CRISPR/Cas9-based therapies.

About 1.5% of the global population (80-90 million people) are carriers of beta-thalassemia. 60,000 symptomatic individuals are born annually.

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