SCD Research Lands Dr. Orkin on Time’s Most Influential People of 2024

Stuart Orkin, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, has been named as one of Time’s 100 Most Influential People of 2024 for his research on fetal hemoglobin and the mechanisms underlying hemoglobinopathies such as sickle cell disease (SCD).

Dr. Orkin’s work dates back to 2008 when a genome-wide association study he led showed that the BCL11A gene controls the switch from fetal hemoglobin to adult hemoglobin production—from γ-globin to β-globin. Subsequently, he and colleagues showed that suppressing BCL11A reactivated the production of fetal hemoglobin in mice.

These findings and additional studies led by Dr. Orkin culminated in the development of exagamglogene autotemcel (exa-cel), a therapy that utilized CRISPR/Cas9 gene-editing technology to suppress BCL11A in red blood cell precursors and unlock the production of fetal hemoglobin in patients with SCD.

Following successful phase III trials, exa-cel, codeveloped by CRISPR Therapeutics and Vertex Pharmaceuticals under the name Casgevy, was approved by the US Food and Drug Administration in December 2023 for the treatment of SCD in patients aged 12 years and older with recurrent vaso-occlusive crises.

While exa-cel is a groundbreaking, potentially curative treatment for SCD, it carries a significant cost that currently serves as a barrier to widespread use. To that end, Dr. Orkin told Time that, “we solved some of the problem, but really haven’t solved what we set out to solve, which is how to make not just a few people but a lot of people better.”