FDA Approves First CRISPR-Based Therapy Kaschey for Sickle Cell Disease and Beta Thalassemia

Alex Hogan reports on the FDA approval of Kaschey, the first CRISPR-based therapy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, to treat sickle cell disease and beta thalassemia. The treatment edits a patient’s own blood stem cells to resume production of fetal hemoglobin, alleviating disease symptoms. The video explains the workflow from extracting stem cells, delivering CRISPR components and Cas9, to growing and freezing edited cells for infusion after chemotherapy to wipe out the existing bone marrow. It also highlights the risks, including hair loss, mouth sores, infertility, weeks in the hospital, and the significant cost and duration of treatment. This marks a milestone in genetic medicine with broad implications for millions of patients.

Overview

The video discusses the FDA approval of Kaschey, the first CRISPR-based therapy, designed to treat sickle cell disease and beta thalassemia by reactivating fetal hemoglobin production in patients’ own blood stem cells. The piece frames this as a landmark moment in genetic medicine and patient care, illustrating both the scientific strategy and the practical considerations of delivering a gene-editing therapy to people who need it.

How Kaschey Works

Kaschey uses CRISPR gene editing to modify a patient’s hematopoietic stem cells so they resume producing fetal hemoglobin, which can carry oxygen more effectively in the context of defective adult hemoglobin. By editing the patient’s cells ex vivo, the therapy bypasses immune rejection and leverages the body’s own stem cell machinery to restore healthier red blood cell function. The approach targets the regulation of hemoglobin expression rather than correcting every mutation directly, creating a therapeutic pathway for both sickle cell disease and beta thalassemia.

The Manufacturing Workflow

The video describes the workflow: a patient’s blood is drawn to isolate stem cells, CRISPR components including Cas9 and a guide RNA are introduced to these cells, and an electroporation process transfers the editing machinery into the cells. The edited cells are cultured, harvested, and then frozen in preparation for infusion. Prior to infusion, patients undergo chemotherapy to wipe out the existing bone marrow, a step that is necessary to create space for the edited cells to engraft. The entire process can span months and requires careful clinical management in a hospital setting.

Risks, Challenges, and Costs

The program highlights several potential downsides: chemotherapy-induced hair loss, mouth sores, and infertility are among the risks. After infusion, patients may spend weeks in the hospital navigating recovery and potential complications. The treatment also carries a substantial price tag and a lengthy production-to-delivery timeline, which pose access and equity challenges for patients and health systems alike.

Implications and Outlook

The approval of Kaschey represents a milestone in genetic medicine, showcasing how autologous cell therapies coupled with gene editing could transform the management of hemoglobinopathies. As the field advances, ongoing monitoring of long-term safety, durability of response, and real-world outcomes will shape the adoption of this technology and its potential expansion to other genetic diseases.