First gene-editing therapy for sickle cell disease approved by US FDA

The U.S. Food and Drug Administration (FDA) on Friday approved a pair of gene therapies for sickle cell disease, including the first treatment based on the groundbreaking Crispr gene-editing technology.

The agency approved Bluebird Bio's Lyfgenia, and a separate treatment called Casgevy by partners Vertex Pharmaceuticals and Crispr Therapeutics.

Both therapies are approved for people aged 12 years and older. The Vertex/Crispr gene therapy uses the groundbreaking gene editing technology that won the inventors the Nobel Prize in 2020.

Sickle cell disease is a painful, hereditary blood disorder that can be disabling and lead to premature death. It affects an estimated 100,000 people in the United States, most of whom are black.

In sickle cell disease, the body produces defective, sickle-shaped hemoglobin, affecting the red blood cells' ability to properly transport oxygen to the body's tissues.

The sickle cells tend to stick together and can block small blood vessels, causing severe pain. It can also lead to strokes and organ failure.

U.S.-listed shares of Crispr therapeutics rose 1.6 percent, while Vertex Pharmaceuticals shares fell 1.4 percent. Shares of Bluebird Bio were halted from trading ahead of the news.

Makers of both therapies have pitched them as one-time treatments, but data on how long their effects last are limited.

The only long-term treatment for sickle cell disease is a bone marrow transplant.

“I'm actually very reluctant to call them a cure. I prefer to call them a transformative therapy because patients on the other end of gene therapy will still have sickle cell disease,” said Dr. Sharl Azar, medical director of the Comprehensive Sickle Cell Disease Treatment Center at Massachusetts General Hospital. Bluebird bio's sickle cell therapy is designed to work by delivering modified genes into the body via disabled viruses to help the patient's red blood cells produce normal hemoglobin.

Vertex's therapy requires patients to have stem cells extracted from their bone marrow. The cells are then sent to production facilities where they are processed using Crispr/Cas9 technology. Once the cells are incubated, they are reinjected into the patient during a month-long hospital stay.

Both gene therapies can last several months and involve high-dose chemotherapy, but this carries potential risks of infertility.

“Not everyone who undergoes chemotherapy will ultimately become infertile, but the majority of them will,” says Dr. Azar.

While the risk can be managed by fertility preservation methods such as egg freezing and sperm banking, this is only covered by insurance for cancer patients undergoing chemotherapy and not for those receiving gene therapy, Dr. Azar said .

He said the out-of-pocket cost for this could be as much as $40,000.

FDA staff also raised concerns about unintended genomic changes resulting from the treatment in documents released ahead of an October meeting of a panel of independent experts on Vertex's therapy.

The company plans to assess potential long-term safety risks through a 15-year post-approval follow-up study.

Vertex's Crispr therapy is also under review by the FDA for another blood disorder, transfusion-dependent beta-thalassemia, with a decision expected on March 30.