The US Food and Drug Administration (FDA) has approved two groundbreaking gene therapies for sickle cell disease, including the first CRISPR-based treatment. Lyfgenia from bluebird bio and Casgevy by Vertex Pharmaceuticals and CRISPR Therapeutics have been approved for people aged 12 years and older.
Sickle cell disease is an inherited blood disorder that can be debilitating and often leads to premature death. It affects an estimated 100,000 people in the US, most of whom are Black. The disease is caused by the body producing flawed, sickle-shaped hemoglobin, which prevents red blood cells from carrying oxygen to the body’s tissues. The sickle cells can stick together and block small blood vessels, leading to intense pain and other complications such as strokes and organ failure.
The gene therapies are based on the breakthrough CRISPR gene editing technology, which won its inventors the Nobel Prize in 2020. Bluebird bio’s sickle cell therapy works by inserting modified genes into the body through disabled viruses to help the patient’s red blood cells produce normal hemoglobin. Vertex’s therapy requires stem cells harvested from the patient’s bone marrow, which are then sent to a manufacturing facility where they are edited using CRISPR/Cas9 technology. Once the cells are incubated, they are infused back into the patient during a month-long hospital stay.
The makers of both therapies are pitching them as one-time treatments, but the data on how long their effect lasts is limited. The only longer-term treatment for sickle cell disease is a bone marrow transplant.
Although the treatments offer hope for those suffering from the disease, there are potential risks associated with them. High-dose chemotherapy is required for both therapies and this can lead to infertility. Dr. Sharl Azar, medical director of the Comprehensive Sickle Cell Disease Treatment Center at Massachusetts General Hospital, says that although not everybody who undergoes chemotherapy will end up having infertility, the majority of them will. Unfortunately, fertility preservation methods such as freezing eggs and sperm banking are not covered by insurance for those receiving gene therapy and can cost up to $40,000 out-of-pocket.
The FDA staff released documents ahead of an October meeting of a panel of independent experts on Vertex’s therapy, which flagged concerns of unintended genomic alterations from the treatment. Vertex plans to assess potential long-term safety risks through a 15-year follow-up study after approval.
The approval of these two gene therapies for sickle cell disease is a major milestone in the fight against the disease. It is a testament to the power of modern science and technology, and offers new hope to those suffering from the condition. It is now up to the healthcare community to make sure that these treatments are accessible to all who need them.
