In a landmark decision, the FDA greenlit two new drugs for the treatment of sickle cell disease in patients 12 and older, one of which —Vertex’s drug Casgevy — is the first approved use of genome editing technology CRISPR in the US. Bluebird Bio’s Lyfgenia also is a cell-based gene therapy, however, it uses a different gene modification technique to deliver tweaked stem cells to the patient.
Both approvals cultivate new pathways for the treatment of sickle cell disease, which is an inherited blood disorder that is characterized by red blood cells that can’t properly carry oxygen, which leads to painful vaso-occlusive crises (VOCs) and organ damage. The disease is particularly common among African Americans and, to a lesser extent, among Hispanic Americans. Bone marrow transplants are currently the only cure for sickle cell disease, but they require well-matched donors and often involve complications.
— Vertex Pharmaceuticals (@VertexPharma) December 8, 2023
While both drug approvals use gene editing techniques, Casgevy’s CRISPR/Cas9 genome editing works by cutting out or splicing in DNA in select areas. Patients first have blood drawn so that their own stem cells can be isolated and edited with CRISPR. They then undergo a form of chemotherapy to remove some bone marrow cells, so the edited stem cells can be transplanted back in a single infusion.
Both drug approvals are based on studies that evaluated the effectiveness and safety of the novel therapies in clinical patients. With Casgevy, study participants reported that they did not experience “severe VOCs” for at least 12 consecutive months during the 24-month follow-up. Similarly, patients on Lyfgenia did not experience a “pain crisis” for six to 18 months after the therapy.
The FDA's decision comes shortly after UK regulators, as well as the National Health Regulatory Authority in Bahrain both approved Vertex’s Casgevy. The approval for a CRISPR-based treatment creates opportunity for further innovation in the gene editing space — for treatments ranging from cancers to heart diseases to Alzheimer’s. “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,” Nicole Verdun, director of the Office of Therapeutic Products at the FDA’s Center for Biologics Evaluation and Research said. Casgevy is still currently under review by the European Medicines Agency.