After birth, fetal hemoglobin production is turned off and replaced by adult hemoglobin, hemoglobin A in healthy individuals. In patients with sickle cell disease, it is replaced by hemoglobin S, leading to the development of sickle shaped red blood cells. “The premise of Casgevy is to use CRISPR to edit the BCL11A gene to flip the switch to enable the production of fetal hemoglobin and thereby preventing the red blood cells from sickling,” says Dr. Bhatia.
Patients who received Casgevy in the clinical trial have had increases in fetal hemoglobin by month 6 that were maintained thereafter, says Dr. Mapara, resulting in little to no severe vaso-occlusive crises in the two year trial.
The treatment is an involved process. “The process to receive this treatment takes several stages, as the person’s own cells must be collected and treated before being delivered back into their body,” adds Dr. Bhatia. “But the changes in hemoglobin have been sustained. With Casgevy, for example, we are seeing patients with greater than 80% of the edited cells in their bone marrow.”
“The therapy has generally been very safe,” she adds. “The side effects we see are more from chemotherapy, such as concerns with infertility, and mental health. In terms of mental health, patients are relieved from the effects of sickle cell disease and do not have to be in the hospital all the time, but they go through a process of learning a new way of life, one without a disease that took so much of their time before.”
Dr. Mapara says that having a dedicated psychiatrist at NewYork-Presbyterian/Columbia University Irving Medical Center to provide psychological support for patients undergoing transplant and treatment was a major asset.
“For adult patients, for example, sickle cell disease has been the center of their existence,” he says. “This has impacted all aspects of their lives, from their jobs, education to social interactions with families and friends. It is important for patients to have support with their mental health during and after therapy, as they navigate life after treatment.”
To continue to evaluate the long-term safety and efficacy of Casgevy, long-term follow up studies on patients who received the therapies is underway.
Says Dr. Bhatia: “As long as patients continue to sustain higher amounts of fetal hemoglobin and the response is durable, then there is a lot of promise for this new treatment.”