FDA Greenlights Casgevy: A Landmark Approval for CRISPR Therapy in Sickle Cell Disease

USA: The U.S. Food and Drug Administration (FDA) has given its approval for Casgevy, the first-ever CRISPR-based gene editing therapy for sickle cell disease (SCD). Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, Casgevy, also known as exagamglogene autotemcel or exa-cel, is a one-and-done treatment that has demonstrated remarkable clinical results. The FDA’s decision, which was anticipated due to the therapy’s success in trials, marks a historic moment in the realm of precision medicine.

Tale of Triumph and Advances in Genetic Science

The approval of Casgevy holds particular significance as it addresses the genetic disorder famously termed “the first molecular disease” by Linus Pauling nearly 75 years ago. The therapy aims to compensate for the SCD mutation by restoring the expression of fetal hemoglobin (HbF), offering a promising avenue for patients suffering from this debilitating condition.

Nobel laureate Jennifer Doudna expressed her admiration, stating, “Going from the lab to an approved [CRISPR] therapy in just 11 years is a truly remarkable achievement.” Doudna emphasized the importance of this approval in addressing a disease that has historically been neglected by the medical establishment.

Unraveling the Casgevy Strategy

Casgevy employs CRISPR-Cas9 gene editing technology to inactivate the BCL11A repressor, ultimately releasing the handbrake on HbF expression. The therapy compensates for the SCD mutation in the β-globin gene, offering a transformative approach to treating the disease.

The identification of the BCL11A target, dating back 15 years, underscores the critical role of fundamental discovery science. Dr. Vijay Sankaran, who played a key role in foundational genome-wide association studies, highlighted the significance of such studies in advancing pivotal medical breakthroughs.

Patients and experts alike celebrated the FDA’s decision. Victoria Gray, the first patient to receive Casgevy, expressed overwhelming joy, saying, “Our prayers were not in vain! This is only the beginning!!!” In Tanzania, Dr. Julie Makani, a leading SCD physician-scientist, described it as a “momentous milestone” with a major impact on therapeutic interventions for SCD.

Despite this triumph, the road ahead remains challenging. SCD, affecting around 100,000 people in the U.S. and millions globally, has a long history of suffering. The approval of Casgevy is a significant step, but it also shines a light on persistent issues in healthcare systems. Profiling, suspicion, and insufficient access to generic drugs and screening tools continue to plague SCD patients.

The Cost of Progress

Casgevy’s approval comes with a notable price tag, as Vertex announced a list price of $2.2 million. Bluebird Bio’s lentiviral therapy, Lyfgenia, approved simultaneously, is priced at $3.1 million. The ex vivo genome editing protocol involving stem cell harvesting and toxic chemotherapy poses challenges in terms of affordability and scalability.

As the gene and cell therapy field celebrates this milestone, the focus shifts to the accessibility of these revolutionary treatments. The journey to making gene editing therapies routine, scalable, safe, and affordable for a broader population is the next frontier. The story of Casgevy is not the end but a significant beginning, inspiring hope for the future of SCD treatment.