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FDA Approves Groundbreaking Cell-Based Gene Therapies for Sickle Cell Disease

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The U.S. Food and Drug Administration (FDA) has approved two groundbreaking treatments, Casgevy and Lyfgenia, marking a significant milestone in the field of gene therapy. These therapies represent the first cell-based gene treatments approved by the FDA for individuals aged 12 and above suffering from sickle cell disease (SCD). Notably, Casgevy is the first FDA-approved therapy to utilize innovative genome editing technology, a remarkable advancement in the realm of gene therapy.

Sickle cell disease is a hereditary blood disorder affecting approximately 100,000 people in the United States, with the highest incidence among African Americans and some Hispanic Americans. The primary issue in SCD is a mutation in hemoglobin, a protein found in red blood cells responsible for oxygen delivery to body tissues. This mutation causes red blood cells to assume a crescent or “sickle” shape, leading to restricted blood flow, diminished oxygen delivery, and severe pain and organ damage referred to as vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). Repeated VOEs can result in life-threatening disabilities and premature death.

Dr. Nicole Verdun, Director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, stated, “Sickle cell disease is a rare, debilitating, and life-threatening blood disorder with significant unmet needs. We are excited to advance the field, especially for individuals whose lives have been severely impacted by the disease, by approving two cell-based gene therapies today. Gene therapy holds the promise of delivering more targeted and effective treatments, particularly for individuals with rare diseases where current treatment options are limited.”

Cutting-edge Cell-based Gene Therapies for Sickle Cell Disease

Casgevy, a cell-based gene therapy, is authorized for treating SCD in patients aged 12 and above who experience recurrent vaso-occlusive crises. Notably, Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a groundbreaking genome editing technology. This involves modifying patients’ hematopoietic (blood) stem cells through CRISPR/Cas9 technology. The modified stem cells are then transplanted into the patient’s body, where they attach to the bone marrow and boost the production of fetal hemoglobin (HbF), a type of hemoglobin that prevents the sickling of red blood cells in SCD patients.

Lyfgenia is another cell-based gene therapy that utilizes a lentiviral vector for genetic modification. It is approved for treating SCD patients aged 12 and above with a history of vaso-occlusive events. In Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, gene-therapy-derived hemoglobin that functions similarly to hemoglobin A found in individuals not affected by SCD. Red blood cells containing HbAT87Q have a lower risk of sickling and obstructing blood flow, offering therapeutic benefits.

Both Casgevy and Lyfgenia are developed using the patient’s blood stem cells, which are modified and then administered as a single-dose infusion during a hematopoietic stem cell transplant. Patients undergo myeloablative conditioning, a process that removes cells from the bone marrow before being replaced with the modified cells in Casgevy and Lyfgenia. Patients who receive these therapies will participate in a long-term study to assess safety and effectiveness.

Sickle Cell Disease

FDA Director Emphasizes Approvals of Innovative Gene Therapies for Sickle Cell Disease

Peter Marks, M.D., Ph.D., the Director of the FDA’s Center for Biologics Evaluation and Research, highlighted the significance of these approvals in the realm of innovative cell-based gene therapies. He stated, “These approvals represent a crucial medical advancement by using innovative cell-based gene therapies to address potentially devastating diseases and improve public health. The FDA’s commitment to facilitating the development of safe and effective treatments for conditions with severe impacts on human health is evident in today’s actions.”

In a trial with 31 patients, Casgevy showed effectiveness by reducing severe VOC episodes in 93.5% of cases, with no graft failures. Common side effects included low blood cell levels, mouth sores, nausea, pain, and fever. In a study of Lyfgenia with SCD patients aged 12 to 50, 88% achieved complete resolution of VOEs between 6 to 18 months after treatment. Common side effects include mouth sores, low blood cell levels, and a risk of blood cancers, warranting lifelong monitoring. Both Casgevy and Lyfgenia received designations for Priority Review, Orphan Drug, Fast Track, and Regenerative Medicine Advanced Therapy from the FDA. Vertex Pharmaceuticals Inc. obtained approval for Casgevy, while Bluebird Bio Inc. received approval for Lyfgenia.

 

Resource: FDA, December 08, 2023

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