The US Food and Drug Administration has approved a pair of gene therapies for sickle cell disease, including the first treatment based on the breakthrough Crispr gene-editing technology, opening two “transformative therapy” pathways for some patients.
The FDA approved Lyfgenia from Bluebird Bio, and a separate treatment called Casgevy from partners Vertex Pharmaceuticals and Crispr Therapeutics. Both therapies are made from the patients’ own blood stem cells and are approved for people 12 years of age and older.
The Vertex/Crispr gene therapy uses the breakthrough gene editing technology that won its inventors the 2020 Nobel Prize. The therapy can be aimed at cutting DNA in targeted areas, allowing the ability to precisely remove, add or replace DNA where it has been 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.
Lyfgenia is a cell-based gene therapy that alters a patient’s blood stem cells to produce a gene therapy-derived hemoglobin that functions similarly to a type of normal adult hemoglobin unaffected by sickle cell disease.
Sickle cell disease is a painful, inherited blood disorder that can be debilitating and lead to premature death. It affects an estimated 100,000 people in the US, is most common in African Americans and, although less commonly, also affects Hispanic Americans.
In sickle cell disease, the body makes defective, sickle-shaped hemoglobin, which impairs the ability of red blood cells to properly transport oxygen to the body’s tissues. The sickle cells tend to stick together and can block small blood vessels, causing intense pain. It can also lead to strokes and organ failure.
“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with a 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 Nicole Verdun, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, said in a statement.
“Gene therapy holds the promise of delivering more targeted and effective treatments, particularly for individuals with rare diseases where current treatment options are limited,” added Verdun.
Manufacturers of both therapies have proposed 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 will still have sickle cell disease on the other side of gene therapy,” says Sharl Azar, medical director of the Comprehensive Sickle Cell Disease Treatment Center at Massachusetts General Hospital.
Both gene therapies can last several months and involve high-dose chemotherapy, but they carry potential risks of infertility.
“Not everyone who undergoes chemotherapy will end up with infertility, but the majority of them will,” Azar said.
Although the risk can be managed through fertility preservation methods such as egg freezing and sperm banking, it is only covered by insurance for cancer patients undergoing chemotherapy and not those receiving gene therapy, Azar said.
He said the out-of-pocket expense on that could be as high as $40,000.
FDA staff in documents released ahead of an October meeting of a panel of independent experts on Vertex’s therapy also flagged concerns about unintended genomic changes from the treatment.
The company plans to evaluate potential long-term safety risks through a 15-year follow-up study after approval.
Reuters contributed to this report
