FDA Approves a CRISPR-Based Medicine to Treat Sickle Cell Disease

WASHINGTON — The Food and Drug Administration on Friday approved the world’s first medicine based on CRISPR gene-editing technology for the treatment of sickle cell disease.

The new treatment, called Casgevy, was manufactured by Vertex Pharmaceuticals, of Boston, Massachusetts, and CRISPR Therapeutics, of Switzerland, using a technology — CRISPR/Cas9 — that can precisely repair DNA mutations.

CRISPR/Cas9 can be directed to cut DNA in targeted areas in a patient’s hematopoietic (blood) stem cells, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. 

The modified blood stem cells are then 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. 

In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.

But Casgevy wasn’t the only milestone advance approved for the treatment of sickle cell disease on Friday.

The agency also approved the use of a cell-based gene therapy called Lyfgenia.

Manufactured by Bluebird Bio Inc., Somerville, Massachusetts, Lyfgenia uses a gene delivery vehicle, also known as a lentiviral vector, for genetic modification.

With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to the normal adult hemoglobin produced in persons not affected by sickle cell disease. 

Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient. 

Both treatments have been approved for patients 12 years of age and older.

Prior to treatment, a patient’s own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia. 

Patients who receive Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness, the FDA said. 

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products within 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,” Verdun added.

Sickle cell disease is a group of inherited, chronic and life-shortening 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 called vaso-occlusive events or vaso-occlusive crises. 

The recurrence of these events or crises can lead to life-threatening disabilities and/or early death.

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