“We’ve had nothing in our field for decades,” said Dr. Sharl Azar, medical director of the Comprehensive Sickle Cell Disease Treatment Center at Mass General Hospital. On Friday that changed. The FDA approved two gene therapies for sickle cell disease, Casgevy and Lyfgenia, and called them “milestone” treatments.
Casgevy is the first CRISPR gene-editing therapy to win FDA approval. Vertex Pharmaceuticals and CRISPR Therapeutics make it. Lyfgenia, from BlueBird Bio, takes a different route and uses a virus to deliver new genetic material. In clinical trials both significantly reduced pain episodes and the need for blood transfusions.
How they work
Casgevy does not remove the mutation that causes the disease. Its edit instead prompts the body to start making healthy red blood cells. Trial results described in a review in Annals of Medicine and Surgery show that, in patients 12 and older, it raises fetal hemoglobin levels and sharply cuts vaso-occlusive events.
Researchers estimate that roughly 20-25% of people with the disease are sick enough to be good candidates. Sickle cell disease affects approximately 100,000 Americans, primarily Black Americans with African ancestry, according to the CDC. One in every 365 Black or African American babies born in the U.S. has it. The abnormal, sickle-shaped red blood cells clog blood flow and cause severe pain, fatigue, infections, stroke and sometimes organ damage. Average life expectancy is roughly 52 years.
Until now the only cure was a bone marrow transplant. It is risky, and most patients cannot get one because it needs a donor match, typically an unaffected sibling.
Patients speak
Dr. Haydar Frangoul, of Sarah Cannon Research Institute, calls the new therapies a “functional cure” and not a true cure, because patients no longer have symptoms. Jimi Olaghere, a clinical trial volunteer treated in Nashville, put it more bluntly. “I’m literally a different person,” he said. Before treatment, he spent most of his time in bed in pain. Now the Atlanta father of three plays with his young children and drives them to school.
Fifteen-year-old Jonathan Lubin had his first pain crisis at 9 months and spent his childhood in and out of the hospital. In the year and more since his CRISPR treatment at New York-Presbyterian/Columbia University Irving Medical Center, he has had none. He plays basketball and drums, and he swims, which cold water used to make impossible. “Maybe the upside would be that I got superpowers!” he joked.
The costs and risks
Neither treatment is simple. The therapy is hard to manufacture and demands months of preparation for patients and their families. Patients stay in the hospital for several weeks and get chemotherapy first, which can threaten fertility, so they will likely be offered fertility preservation.
The FDA says patients should be counseled about “off target” effects, a hypothetical risk of unintended consequences from gene editing. Lyfgenia carries a “black box” warning, the agency’s highest-level safety alert, about a potential risk of blood cancer.
FDA biologics chief Dr. Peter Marks said the approvals show “the continued momentum of this promising new area of medicine.” Frangoul gave the credit to the volunteers: “The heroes of the story are not the physicians or the basic scientists,” he said. “They are the patients.”
Sources
- FDA approves gene therapies for sickle cell disease, a 'functional cure' for many
- Revolutionary breakthrough: FDA approves CASGEVY, the first CRISPR/Cas9 gene therapy for sickle cell disease
