FDA Approves Groundbreaking Gene-Editing Therapies for Sickle Cell Disease

In a historic decision, the Food and Drug Administration (FDA) has granted approval for the first-ever gene-editing treatment aimed at mitigating human illness. This groundbreaking development encompasses two gene therapies specifically designed for individuals aged 12 and above grappling with the most severe manifestation of sickle cell disease, an agonizing blood disorder that has long been overlooked in medical research.

Dr. Nicole Verdun, the director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, expressed enthusiasm, stating, “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.”

The approval marks significant milestones in both sickle cell treatment and the swiftly advancing domain of gene editing, generating anticipation for addressing numerous diseases. Dr. Verdun emphasized the potential of gene therapy, stating, “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.”

Jennifer Doudna of the University of California, Berkeley, a key figure in the discovery of the CRISPR gene-editing technique employed in one of the sickle cell treatments, conveyed her excitement, stating, “I’m elated, excited, in awe. It’s an exciting day and the beginning of a new day in medicine.”

The CRISPR treatment, developed collaboratively by Vertex Pharmaceuticals and CRISPR Therapeutics, involves extracting cells from the patient’s bone marrow, editing a gene using CRISPR, and then reintroducing billions of modified cells back into the patient. This process prompts the production of fetal hemoglobin, restoring normal red blood cell function. While not a definitive cure, the therapy, named Casgevy, is designed as a one-time treatment expected to alleviate symptoms for a lifetime.

According to data presented to the FDA, the CRISPR treatment resolved severe pain crises for 96.7% of subjects for at least 18 months, demonstrating promising results. Another gene therapy, Lyfgenia, developed by bluebird bio inc., received FDA approval for sickle cell treatment without utilizing CRISPR. Instead, Lyfgenia employs a conventional gene therapy approach using a virus to transport a gene into cells.

However, the approval’s celebratory tone is tempered by concerns about accessibility and cost. Both treatments are priced significantly, with Casgevy at $2.2 million and Lyfgenia at $3.1 million wholesale. Additionally, the complex and labor-intensive procedures involved may pose challenges for many hospitals, limiting accessibility for patients.

“We have a lot more work to do,” cautioned Doudna, emphasizing the need to make gene-editing treatments widely available.

 

Sickle cell disease, caused by a genetic defect leading to abnormal hemoglobin production, results in misshapen red blood cells that cause severe pain and organ damage. Primarily affecting individuals of African, Middle Eastern, and Indian descent, sickle cell is a rare yet prevalent genetic disorder.

While bone marrow transplants offer a potential cure for some patients, the majority struggle to find suitable donors. Approximately 20,000 severe cases in the U.S. could potentially benefit from the CRISPR treatment.

Dr. Lewis Hsu, a pediatric hematologist at the University of Illinois at Chicago, expressed excitement, stating, “This is something that we’ve been waiting for in the sickle cell community for basically 70 years. This is a very big deal.”

The approval holds personal significance for Victoria Gray, a sickle cell patient from Forest, Miss., who became the first person to receive the CRISPR treatment in the U.S. in 2019. Reflecting on the approval, Gray said, “I’m ecstatic. It’s a blessing that they approved this therapy. It’s a new beginning for people with sickle cell disease.” She described the treatment as transformative, allowing her to lead a more energetic life, work full time, and spend quality time with her children.

Despite these positive outcomes, concerns persist regarding the technical complexity and lengthy hospitalization required for the treatments. The intricate procedures involve multiple hospital visits, bone marrow transplants, and extended hospital stays, potentially deterring patients due to physical and logistical challenges.

Melissa Creary, an assistant professor at the University of Michigan studying sickle cell, acknowledged the promise of technology but cautioned about potential disparities, stating, “I am excited about the promise that this technology has for those living with sickle cell disease. But as this technology comes to market, it’s going to be really interesting to see the ways in which profit overtake social justice.”

The geographical and financial challenges of accessing treatment also raise concerns. Many countries lack the necessary medical infrastructure for these advanced treatments, and even in the U.S., availability may be limited.

Doudna, leading a center at Berkeley focused on simplifying gene-editing treatments, and the National Institutes of Health are actively working to address these challenges. Biotech companies are collaborating with insurers to explore coverage options. Advocates argue that the high upfront costs may be justified by the long-term savings from avoiding lifelong sickle cell complications.

Amid these developments, concerns about potential “off-target” effects and unintended consequences of gene editing persist. The FDA has issued a warning about Lyfgenia, which employs a more conventional gene therapy approach, potentially increasing the risk of blood cancer.

The companies involved plan to monitor patients for 15 years to assess the treatment’s longevity, effectiveness, and potential long-term complications. CRISPR-based treatments also show promise in addressing other conditions, such as amyloidosis and familial hypercholesterolemia.

“This is only the beginning,” remarked CRISPR researcher Doudna, underscoring the ongoing evolution of gene-editing technologies.