FDA approves “milestone” sickle cell disease treatments

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In what it calls a “milestone” development, the U.S. Food and Drug Administration (FDA) announced it has approved the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients age 12 and older.

One of the therapies, Casgevy, is the first FDA-approved treatment to use a novel type of gene editing technology, signaling an innovative advance in gene therapy.

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in the announcement. He added that they reflect “the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”

Sickle cell disease is a group of inherited blood disorders affecting approximately 100,000 people in the U.S. It is most common in African Americans and, while less prevalent, also affects Hispanic Americans. The primary problem in sickle cell disease is a mutation in hemoglobin, a protein found in red blood cells that delivers oxygen to the body’s tissues. This mutation causes red blood cells to develop a crescent or “sickle” shape.

These sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading to severe pain and organ damage leading to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). Their recurrence can lead to life-threatening disabilities and/or early death.

Casgevy, a cell-based gene therapy, is approved for treating sickle cell disease in patients 12 and older with recurrent vaso-occlusive crises. It is the first FDA-approved therapy to utilize CRISPR/Cas9, a type of genome editing technology.

Patients’ blood stem cells are modified by genome editing using CRISPR/Cas9 technology. The modified blood stem cells are transplanted back into the patient where they attach and multiply within the bone marrow and increase the production of fetal hemoglobin, a type of hemoglobin that facilitates oxygen delivery.

The second approved treatment, Lyfgenia, is a cell-based gene therapy that uses a gene delivery vehicle for genetic modification. Like Casgvey, it is approved for treating patients age 12 years and older with sickle cell disease and a history of vaso-occlusive events.

Both products are made from the patients’ own blood stem cells, which are modified and given back as a one-time, single-dose infusion as part of a blood stem cell transplant. Patients receiving Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness. 

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field…by approving two cell-based gene therapies today,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research. “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.”