This FDA approval represents the first cell-based gene therapies for the treatment of sickle cell disease in patients 12 years of age and older.
The FDA has approved 2 cell-based gene therapy treatments, Casgevy (Vertex Pharmaceuticals Inc.) and Lyfgenia (Bluebird Bio Inc.), for the treatment of sickle cell disease (SCD) in patients who are 12 years of age and older. With this approval, Casgevy is the first treatment that utilizes CRISPR/Cas9, a novel genome editing technology, to be approved by the FDA.
Casgevy is indicated for the treatment of SCD in patients at least 12 years of age with recurrent vaso-occlusive crises (VOCs). CRISPR/Cas9 can be directed to cut DNA in targeted areas, allowing accurate editing—removing, adding, or replacing segments—where the DNA was cut. The modified blood stem cells are then re-inserted back into the patient where they attach and multiply within the bone marrow, increasing the production of fetal hemoglobin (HbF), which facilitates oxygen delivery and prevents the sickling of red blood cells.
Lyfgenia, which uses a lentiviral vector (gene delivery vehicle) for genetic modification, is indicated for the treatment of patients at least 12 years of age with SCD and a history of vaso-occlisove events (VOEs). Lyfgenia modifies the patient’s blood stem cells to produce HbAT87Q, hemoglobin derived with gene therapy that has a similar function to the normal adult hemoglobin produced in individuals without SCD, hemoglobin A. Further, red blood cells that have HbAT87Q have a lower risk of sickling and obstructing blood flow in patients.
“SCD is a rare, debilitating, and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving 2 cell-based gene therapies today,” said Nicole Verdun, MD, director of the office of therapeutic products, Center for Biologics Evaluation and Research, FDA, in a press release. “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.”
The safety and efficacy of Casgevy were evaluated in an ongoing single-arm, multicenter trial that enrolled adult and adolescent patients with SCD. In the 2 years prior to screening, patients had a history of at least 2 protocol-defined severe VOCs. The primary efficacy outcome was the absence of severe VOC episodes for at least 12 consecutive months during a 24-month follow-up period. Of the 44 patients who were treated with Casgevy, 31 were evaluable with 29 (93.5%) meeting the primary outcome. Further, all treated patients had successful engraftment, and no patients experiencing graft failure or rejection.
The safety and efficacy of Lyfgenia were based on analysis data from a single-arm, 2-year multicenter study that enrolled patients with SCD who had a history of VOEs between the ages of 12 and 50 years. Efficacy was evaluated based on no occurrences of VOEs between 6 and 18 months after Lyfgenia infusion. Of the 32 patients treated with Lyfgenia, 28 (88%) achieved a complete resolution of VOEs during the time period.
The most common adverse effects (AEs) reported by patients treated with Casgevy were low levels of platelets and white blood cells, sores in the mouth, nausea, vomiting, musculoskeletal pain, abdominal pain, itching, febrile neutropenia (fever with low white blood cell count), and headache. Further, the most common AEs reported by patients treated with Lyfgenia were consistent with chemotherapy and underlying disease, including febrile neutropenia; low levels of platelets, white blood cells, and red blood cells; and stomatitis—sores in the mouth, lips, and throat.
“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the press release. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”
US Food and Drug Administration. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. News release. December 8, 2023. Accessed December 8, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease