Today, December 8, 2023, the United States Food and Drug Administration ("FDA") emulated its British equivalent, the Medicines and Healthcare products Regulatory Agency, by approving the CRISPR/Cas9-based therapy Casgevy, a gene editing treatment for sickle cell disease ("SCD"). As it did in the United Kingdom, this approval marks a milestone in therapeutic history in the United States. Here is how the FDA described Casgevy:
Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.
CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.
The safety and effectiveness of Casgevy were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection.
The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.
The FDA granted the license for Casgevy to biotechnology firm, Vertex Pharmaceuticals Inc.. However, many other biotechnology and pharmaceutical companies are waiting in the line for the FDA to grant approval to their genome editing therapies.