David Shyr, MD, on Surprising Findings With CRISPR Cell Therapy Nula-Cel in Sickle Cell Disease

“When she recovered, she was making mostly hemoglobin F, which was a surprise to us because our gene therapy does not alter hemoglobin F in any way. So, we're happy to report 1 year out. She has a stable hemoglobin around 10-11, a good healthy platelet count near 100, normal white blood cell count, normal neutrophil count, and she has only 3% hemoglobin S, and mostly hemoglobin F. And she's feeling great. No more pain crisis. So very unexpected, and the mechanism of this therapeutic benefit is currently not known. So, there's a lot of investigation with the sponsor ongoing.”

The first patient with sickle cell disease (SCD) treated with CRISPR/Cas9-edited cell therapy KMAU-001 (nulabeglogene autogedtemcel; Kamau Therapeutics) in a phase 1/2 clinical trial(NCT04819841) has shown a marked improvement in quality of life with zero vaso-occlusive events (VOEs) or other manifestations of SCD. However, the mechanism of the therapeutic benefit is unknown, with the patient first experiencing low cell counts and decreasing amounts of the corrected hemoglobin A allele. The patient recovered after receiving eltrombopag and became transfusion-independent, however, investigators found that she was mostly producing fetal hemoglobin, which KMAU-001 is not designed to have an effect on.

Findings on the patient were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California, by David Shyr, MD, clinical assistant professor, pediatric stem cell transplantation, Stanford Medicine. CGTLivespoke with Shyr to learn more about the unexpected findings and the ongoing research to better understand the case study.

Click here to view more coverage of the ASH 2023 meeting.

REFERENCE

Shyr DC, Lowsky R, Miller W, et al. One Year Follow-up on the First Patient Treated with Nula-Cel: An Autologous CRISPR/Cas9 Gene Corrected CD34+ Cell Product to Treat Sickle Cell Disease. Presented at: ASH 2023 Annual Meeting; December 9-12; San Diego, California. Abstract 5000