sickle cell disease: US FDA approves two gene therapies for sickle cell disease

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The U.S. Food and Drug Administration (FDA) on Friday approved two gene therapies for sickle cell disease, including one that is the first treatment in the United States based on the Nobel Prize-winning CRISPR gene editing technology.

Casgevy, developed by partners Vertex Pharmaceuticals and CRISPR Therapeutics, and bluebird bio’s Lyfgenia were approved for people aged 12 years and older.

CRISPR, discovered by Jennifer Doudna and CRISPR Therapeutics co-founder Emmanuelle Charpentier, uses molecular “scissors” to trim faulty parts of genes that can then be disabled or replaced with new strands of normal DNA.

Bluebird’s gene therapy is designed to work by inserting modified genes into the body through disabled viruses.

Sickle cell disease is a painful, inherited blood disorder in which the body makes flawed, sickle-shaped hemoglobin, impairing the ability of red blood cells to properly carry oxygen to the body’s tissues.

The disease, which can be debilitating and lead to premature death, affects an estimated 100,000 people in the United States, most of whom are Black. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. Sickle cells tend to stick together and can block small blood vessels, causing intense pain. They also can lead to strokes and organ failure.

In separate clinical trials, both the treatments helped reduce painful episodes in patients with the disease, with 29 of 31 patients receiving Casgevy, and 28 of 32 patients on Lyfgenia showing improvement.

U.S.-listed shares of CRISPR Therapeutics were up 1.6%, while Vertex Pharmaceuticals’ stock was down 1.4%. Shares of bluebird bio fell 20%.

Vertex’s stock has risen more than 20% so far this year, while CRISPR was up over 70%.

The drugmakers have pitched their therapies as one-time treatments, but data on how long their effect lasts is limited. The only longer-term treatment for sickle cell disease is a bone marrow transplant.

Other standard care for sickle cell patients have been chemotherapy drug hydroxyurea, or once-daily drugs such as Pfizer’s Oxbryta, which aim to slow the breakdown of red blood cells.

For Vertex’s therapy, patients must have stem cells harvested from their bone marrow. The cells are then sent to manufacturing facilities 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.

Treatment with the gene therapies can take several months and involve high-dose chemotherapy, with a potential risk of infertility.

The FDA has added a black box warning for Lyfgenia informing patients about the risk of blood cancer. Patients receiving the treatment should have lifelong monitoring for the cancer, the regulator said.

FDA staff in documents released a few months ago had also flagged concerns of unintended genomic alterations from Vertex’s treatment.

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

Vertex’s CRISPR therapy is also under an FDA review for another blood disease, transfusion-dependent beta thalassemia, with a decision expected by March 30.

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