In a major development, the FDA has approved two new drugs to treat sickle cell disease in patients 12 and older. One of these, Vertex’s Casgevy, is the first use of CRISPR genome editing technology in the US. The other, Bluebird Bio’s Lyfgenia, is a cell-based gene therapy that uses a different gene modification technique to deliver modified stem cells to patients.
These approvals open up new avenues for the treatment of sickle cell disease, an inherited blood disorder characterized by red blood cells that cannot properly carry oxygen, leading 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 the disease, but they require well-matched donors and often have complications.
While both drugs use gene editing techniques, Casgevy’s CRISPR/Cas9 genome editing works by cutting out or splicing in DNA in specific areas. Patients have their blood drawn so that their own stem cells can be isolated and edited with CRISPR, then undergo a form of chemotherapy to remove some bone marrow cells, allowing the edited stem cells to be transplanted back in a single infusion.
Both drug approvals are based on studies that evaluated the effectiveness and safety of the therapies in clinical patients. Casgevy study participants reported not experiencing severe VOCs for at least 12 consecutive months during the 24-month follow-up, while Lyfgenia patients did not experience a pain crisis for six to 18 months after the therapy.
The FDA’s decision comes shortly after Vertex also received approval for a treatment, creating opportunities for further innovation in the gene editing space for a range of treatments, from cancers to heart diseases. “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,” said Nicole Verdun, director of the Office of Therapeutic Products at the FDA. Casgevy is still under review by the European Medicines Agency.