FDA Approves First CRISPR-Based Gene Therapy

Last week marked a monumental regulatory decision for CRISPR-based gene editing technologies. The United States Food and Drug Administration (FDA) approved the first two cell-based gene therapies for people with sickle cell disease (SCD). Among these two approvals was the first FDA-approved CRISPR-based gene editing therapy, Casgevy, manufactured by Vertex Pharmaceuticals. Bluebird Bio secured the other SCD therapy approval for its drug Lyfgenia.

“Sickle cell disease 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 two cell-based gene therapies today,” said Nicole Verdun, MD, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, in the FDA 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.” 

Casgevy is approved for sickle cell disease patients 12 or older with recurrent vaso-occlusive crises. The therapy uses CRISPR/Cas9 genome-editing technology to edit the erythroid-specific enhancer region of the BCL11A gene in CD34+ hematopoietic stem cells (HSCs).

The FDA notes that, in SCD patients with a history of two or more severe vaso-occlusive crises, Casgevy eliminated severe vaso-occlusive crises for one year in 93.5% of participants. Despite the efficacy, the drug has side effects such as low platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia, headache, and itching.

According to the Vertex press release, there are activated authorized treatment centers that can offer Casgevy in the following locations, and more will be established moving forward:

• Boston Medical Center
• Children’s National Hospital
• City of Hope Children’s Cancer Center
• Medical City Children’s Hospital
• Methodist Children’s Hospital
• Nationwide Children’s Hospital
• The Children’s Hospital at TriStar Centennial
• The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute 
• University of Chicago/Comer Children’s Hospital

Beyond the approval of Casgevy, Lyfgenia was also approved for SCD patients 12 and older with a history of vaso-occlusive events. The treatment works by inserting a functional beta-globin gene into the patient's HSCs.

The treatment’s approval was supported by a two-year multicenter study where 88% of patients treated with Lyfgenia experienced complete resolution of vaso-occlusive events. Throughout the study, researchers identified side effects, including stomatitis, febrile neutropenia, and low platelets, white blood cells, and red blood cells.

The Bluebird press release states, “Lyfgenia will be available at Bluebird Bio’s established network of Qualified Treatment Centers (QTCs), which receive specialized training to administer complex gene therapies like Lyfgenia.”