FDA approves gene therapies for sickle cell disease, a 'functional cure' for many

The U.S. Food and Drug Administration (FDA) on Friday announced that it has approved Casgevy, the first CRISPR gene-editing therapy for sickle cell disease, paving the way for thousands of patients in the U.S. to receive a treatment that has been described as a "functional cure" for eligible patients.

The FDA also approved a gene therapy called Lyfgenia. Collectively, these two therapies represent two "milestone" treatments for sickle cell disease, according to the FDA announcement.

Sickle cell disease is a genetic condition that affects approximately 100,000 Americans – primarily Black Americans with African ancestry, according to the Centers for Disease Control and Prevention (CDC).

Researchers estimate that roughly 20-25% of those with the disease are sick enough that they would be good candidates for the newly approved treatments, which were approved for people aged and older.

Although historic, the new treatments come with significant hurdles and potential risks. The treatment is difficult to manufacture and requires months of preparation for patients and their families. Patients will need to stay in the hospital for several weeks, and will receive preemptive chemotherapy that can place fertility at risk. Because of this, patients will likely be offered preemptive fertility preservation.

Still, in a world with few options, doctors and patients say this is a historic step forward.

"We've had nothing in our field for decades," said Dr. Sharl Azar, Medical Director of the Comprehensive Sickle Cell Disease (SCD) Treatment Center at Mass General Hospital. "So this is part of the reason why this is such a large, seismic shift for us."

“Today's approvals demonstrate the continued momentum of this promising new area of medicine,” said Dr. Peter Marks, Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, speaking during a media briefing Friday.

President Joe Biden on Friday issued a statement praising the FDA’s approval of the new sickle cell disease treatments, calling it a "significant medical advancement" that "holds tremendous promise for developing additional life-saving treatments and it gives hope to the millions of Americans who live with other rare diseases."

According to the CDC, one out of every 365 Black or African American babies born in the U.S. is born with sickle cell disease, which is characterized by abnormal 'sickle'-shaped red blood cells that can clog blood flow, causing severe pain episodes, fatigue, infections, stroke and sometimes organ damage and other complications. The average life expectancy for those living with sickle cell disease is roughly 52 years old.

The only cure is a risky bone marrow transplant – an option that is out of reach for most patients because it requires a donor match, typically an unaffected sibling.

The new treatments are technically not a cure in the same way a bone marrow transplant would be.

"What we are calling it is a 'functional cure,'" said Dr. Haydar Frangoul, Medical Director of Pediatric Hematology/Oncology at Sarah Cannon Research Institute and HCA Healthcare's The Children's Hospital At TriStar Centennial. "I think it is better described by the fact that patients do not have any symptoms."

Many of the clinical trial volunteers who have already undergone treatment say they have a new lease on life.

"I'm literally a different person," said Jimi Olaghere, an early clinical trial volunteer for the Casgevy CRISPR trial, who was treated at the Sarah Cannon Research Institute in Nashville. "Before, my life was me most of the time in bed writhing in pain, not present because of all the pain medications."

Today, the Atlanta-based father of three says he takes joy in playing with his young children, picking them up and driving them to school.

"After this treatment, I have bounds and bounds of energy that I never imagined I'd ever have in my life," says Olaghere.

The treatment Olaghere received is made jointly by Vertex Pharmaceuticals and CRISPR Therapeutics and is the first FDA-approved treatment that uses the genetic modification therapy CRISPR. Often referred to as "genetic scissors," CRISPR technology allows for easier and more precise gene editing than previous methods. The researchers behind the system won the Nobel Prize in 2020.

Rather than editing out the genetic mutation that causes sickle cell disease, the treatment instead makes another edit that prompts the body to start making healthy red blood cells.

The second FDA-approved gene therapy, Lyfgenia, made by BlueBird Bio, works differently, using a virus to deliver new genetic material. Both treatments significantly reduced pain episodes and the need for blood transfusions among patients who were treated as part of the clinical trials.

The FDA says patients who get these treatments should be counseled on so-called “off target” effects, a hypothetical risk about potential unintended consequences of gene editing. The BlueBird Bio treatment has a 'black box' warning -- the FDA's highest-level safety alert -- about the potential risk of blood cancer.

Fifteen-year-old Jonathan Lubin, who received the CRISPR treatment as part of a clinical trial at New York-Presbyterian/Columbia University Irving Medical Center, says he wasn't intimidated by a treatment that would permanently edit his genes.

"I mean, it was pretty cool," said Lubin. "Maybe the upside would be that I got superpowers! You never know."

Lubin experienced his first pain crisis at 9 months old. Throughout his childhood, he was in and out of the hospital every few months. His parents were fearful he might die.

Since his treatment more than a year ago, he hasn't had a pain crisis. He's been able to enjoy his favorite activities, like basketball, playing the drums, and even swimming – an activity that was always out of reach because the water temperature could trigger a pain crisis.

Doctors say the new approved treatments are the first step toward a more hopeful future for patients with sickle cell disease.

"Well, I am very hopeful and very excited," said Dr. Frangoul. "CRISPR used to be science-fiction correct five years ago, and now it is reality."

Frangoul says the scientific advances wouldn't have happened without volunteers like Lubin and Olaghere.

"The heroes of the story are not the physicians or the basic scientists that discovered this. They are the patients that … showed the world that this could be done," Frangoul said. "I think they are the heroes."