Breakthrough Treatments Offer Hope for Black Patients
Regulators have granted approval for two groundbreaking gene therapies designed to treat sickle cell disease. This inherited blood disorder predominantly affects Black individuals in the U.S. The treatments, which consist of one-time therapies, are targeted at patients aged 12 and above who suffer from severe forms of the disease. The first therapy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, is the inaugural therapy of its kind based on CRISPR, the Nobel Prize-winning gene editing tool. The second therapy, created by Bluebird Bio, takes a different approach.
Addressing an Unmet Need
Dr. Nicole Verdun of the FDA celebrated the approvals, emphasizing the significance of these advancements for individuals whose lives have been severely impacted by sickle cell disease. The two gene therapies are the first of their kind to be approved in the U.S., following the FDA’s previous authorization of 15 gene therapies for various other conditions. It is worth noting that some of these treatments have carried list prices in the millions of dollars, and the sickle cell therapies will likely follow suit.
Prevalence and Symptoms
In the U.S., an estimated 100,000 people currently live with sickle cell disease, with approximately one-fifth of them experiencing the severe form. The disease is most prevalent among Black individuals, and on a national scale, 1 in 365 Black babies are born with sickle cell. The high occurrence of sickle cell in regions that are prone to mosquitoes, such as Africa, suggests that being a carrier of the sickle cell trait may help protect against severe malaria.
Sickle cell disease affects hemoglobin, the protein responsible for carrying oxygen in red blood cells. Due to a genetic mutation, these cells become sickle or crescent-shaped, leading to blocked blood flow, excruciating pain, organ damage, strokes, and other severe complications.
Current Treatments and Limitations
Current treatments for sickle cell disease involve medications and blood transfusions. However, the only permanent solution is a bone marrow transplant, which necessitates finding a closely matched donor and carries the risk of rejection. The newly approved gene therapies bypass the need for a donor and instead permanently modify the patient’s blood cells’ DNA.
Vertex’s therapy, known as Casgevy, aims to restore the production of fetal hemoglobin, present at birth and absent in sickle cell disease. CRISPR is utilized to disable a specific gene in the patient’s stem cells. Bluebird’s treatment, called Lyfgenia, involves introducing copies of a modified gene that enables red blood cells to produce “anti-sickling” hemoglobin, preventing or reversing the misshapen cells.
Patient Experiences and Considerations
For many patients, the severity of sickle cell disease makes gene therapy an appealing option. Jalen Matthews, a sickle cell patient from Louisville, Kentucky, expressed her desire to explore gene therapy as a potential cure. Having experienced the disease’s debilitating consequences, including a spinal cord stroke, Matthews believes that a one-time cure could be life-changing. Nevertheless, patients and doctors must consider possible side effects and long-term outcomes.
Challenges and Potential Impact
Despite the promising results from clinical trials, there are concerns regarding side effects and long-term effects. The necessary chemotherapy in both therapies carries risks such as infertility, hair loss, and susceptibility to infections. Bluebird’s therapy has been associated with instances of blood cancer, leading the FDA to include a “black box warning” on the label. Additionally, scientists worry about potential unintended changes to a person’s genome with CRISPR.
Experts anticipate that not all medical centers will offer gene therapies due to the significant equipment and specialized coordination required. Furthermore, the cost could present a considerable obstacle, with Bluebird Bio priced at $3.1 million and Vertex at $2.2 million. The actual cost for patients will depend on insurance coverage and other factors. The U.S. Centers for Medicare and Medicaid Services have proposed a plan to establish partnerships with state Medicaid agencies and drug companies to help cover these expenses.
Although challenges remain, doctors believe that gene therapy has the potential to transform the landscape of sickle cell disease. Dr. Monica Bhatia, a specialist in treating sickle cell disease at NewYork-Presbyterian, envisions a future where these therapies offer significant benefits for patients. Jalen Matthews, along with the sickle cell community, shares this hope and considers the gene therapies a blessing that will positively impact their lives.