FDA APPROVES TWO SICKLE CELL THERAPIES, INCLUDING ONE USING GENE EDITING TOOL

In a major advance, the Food and Drug Administration on Friday approved two gene therapies that target sickle cell disease, one of which is the first commercially available treatment in the United States based on gene editing technology. The historic move offers hope for a long-overlooked genetic illness that can cause excruciating pain and cut decades off people’s lives. It also cracks the door open for a new era in medicine.

One of the new treatments, named Casgevy, is based on CRISPR, a geneediting tool that moved lightning-fast from a scientific breakthrough in 2012 to a therapy that can alleviate suffering. In the wake of the FDA approval, experts anticipate that treating sickle cell disease will be the first of many medical applications for this technology.

The other treatment, developed by Bluebird Bio and called Lyfgenia, uses a harmless virus to insert a gene into a patient’s stem cells. The treatments are approved for patients 12 and older who experience repeated pain episodes.

“I’ve been taking care of kids with sickle cell for over 30 years, and I’ve been waiting for something like this to happen for a long, long time,” said Lewis Hsu, chief medical officer of the Sickle Cell Disease Association of America and a pediatric hematologist at the University of Illinois at Chicago.

In clinical trials, both therapies freed the overwhelming majority of patients from severe pain crises. Several of the patients who received Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, testified before a federal advisory committee in late October, sharing emotional stories about how the therapy opened up their lives, giving them the ability to work or attend school, be present with their families and imagine a future.

In the United States, an estimated 100,000 people, most with African ancestry, have sickle cell disease. About 20,000 of them have severe symptoms, with frequent pain episodes and the potential for organ damage, and would be good candidates for this therapy, said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.

Sickle cell disease is caused by a mutation in a gene that contains the instructions for hemoglobin, an oxygen-carrying protein found inside red blood cells. The abnormal hemoglobin causes red blood cells, normally disc-shaped and pliable, to collapse into rigid, sickle-shaped crescents that clump together and die early. The disease varies in severity from person to person, but blockages caused by the clumped cells can trigger crippling pain and starve organs of oxygen.

There are several therapies for sickle cell disease but only one cure: a bone marrow transplant, typically from a matched sibling. Bone marrow cells from a healthy donor produce normal hemoglobin, allowing transplant patients to live pain-free. But the procedure comes with risks, and only about a fifth of patients are able to find a match.

Gene editing gets around the problem because it turns a person’s own cells into a treatment. Casgevy takes advantage of the fact that before birth, the body produces a form of fetal hemoglobin, and red blood cells that carry it don’t sickle. Casgevy disables a genetic switch that represses the production of fetal hemoglobin after birth, flipping production back on so the body makes red blood cells that don’t sickle.

Lyfgenia uses a harmless virus to modify patient’s cells so that they create a form of hemoglobin that doesn’t sickle. The treatment will carry a black box, the FDA’s most stringent warning, due to the risk of cancer. In a clinical trial, two patients in a clinical trial developed acute myeloid leukemia and died.

“The potential that these products have to transform the lives of patients living with sickle cell disease is enormous,” the FDA’s Marks said.