Why Sickle Cell Gene Therapy Is Slow to Gain Patient Adoption

By Deena Beasley

LOS ANGELES – Student Zoe Davis, 20, found herself hospitalized again this month due to severe sickle cell pain, just weeks into her junior year. Determined to manage the increasingly frequent and debilitating attacks affecting her arms, legs, and abdomen, she is exploring options for relief.

Davis is aware that innovative gene therapies might offer long-term solutions for the approximately 100,000 Americans battling sickle cell disease. However, she is hesitant to embrace these new treatments. "It is so new … I wanted to see more success stories before I committed to it," said Davis, who is pursuing veterinary science at North Carolina Agricultural and Technical State University.

This hesitation highlights a significant reason behind the slower-than-expected adoption of these potentially transformative therapies, which can cost between $2 million to $3 million in the U.S. According to healthcare professionals, younger patients are often reluctant to add more medical burdens to their lives, weighing the demands of school against their health. Dr. Leo Wang, a hematologist-oncologist at City of Hope Children’s Cancer Center near Los Angeles, noted, "Some kids are just not interested." He added that while patients aged 20 to 40 are more inclined, many have such severe forms of the disease that they are not suitable candidates for treatment.

Approved in the U.S. last December, these one-time therapies have been administered to around 100 individuals globally, including those in clinical trials. They involve chemotherapy, which poses risks of cancer and infertility, prompting some patients to consider the lengthy and complex treatment timeline—up to a year—especially if their condition isn’t critical.

Globally, an estimated 8 million people live with sickle cell disease, an inherited disorder, with a significant portion of these individuals in the U.S. being Black. The disease causes red blood cells to take on a "sickle" shape, which can block blood flow, resulting in excruciating pain, potential strokes, organ damage, and early mortality. The genetic mutation responsible for sickle cell disease is most commonly found in regions where malaria is prevalent, as carrying a single copy of the gene can provide protection against malaria.

As of September, at least 30 patients worldwide had begun gene therapy outside of clinical trials, according to drug manufacturers. The procedures require a comprehensive process where patients have their bone marrow stem cells removed and genetically modified in a laboratory. Following this, they undergo chemotherapy and remain in the hospital for several weeks for monitoring after the reinfusion of modified cells.

Medical professionals anticipate that the use of these therapies may increase as more information regarding their safety and efficacy becomes available. However, many patients are still on the sidelines, dealing with considerations such as pregnancy planning, insurance approvals, and the daunting process involved. Some younger patients are still managing their sickness effectively with standard treatments, while older patients often face complications that limit their candidacy.

"You have to be sick, but not too sick," noted Dr. Andrew Campbell, director of the Children’s National Comprehensive Sickle Cell Disease Program in Washington, D.C.

Experts report that over 80% of U.S. patients are unsuitable for these therapies, which are currently only approved for those over 12 with a history of severe pain crises. Recently, one of the drug manufacturers reduced its forecast for the number of patients expected to use its therapies, indicating lower-than-anticipated uptake.

Despite the scientific promise of these therapies, early adopters are largely expected to be patients with severe forms of the disease. Existing treatments for sickle cell include blood transfusions, opiates for severe pain, and hydroxyurea, a generic medication that helps normalize the shape of red blood cells.

Until recently, bone marrow transplants were the only curative option, but they pose challenges in finding compatible donors and also require chemotherapy, which carries the risk of rejection. Individuals with sickle cell disease are advised to avoid temperature extremes, alcohol, smoking, high altitudes, strenuous physical activities, and stress, all of which can trigger painful crises.

For students like Davis, relocating to college in Virginia has exacerbated her condition. Despite taking hydroxyurea and folic acid daily, she still experiences frequent pain episodes that require medical attention.

Kayla Smith Owens, a 25-year-old advocate for sickle cell awareness, shared her challenges with the treatment process. Initially accepted into a bone marrow transplant trial, her potential donor became unavailable. While she is keen on pursuing gene therapy recommended by her doctors due to her age and minimal organ damage, uncertainties regarding her insurance coverage complicate the situation.

Health insurers are enforcing strict criteria for coverage, and some patients have faced denial for treatments recommended by their physicians. In the context of fertility concerns, both Vertex and Bluebird offer financial assistance programs, but these are not available to individuals enrolled in Medicaid, which covers a significant number of sickle cell patients in the U.S.

Following the infusion of approved therapies, early trial results have shown promising outcomes, with a majority of patients experiencing a significant reduction in severe pain crises for at least a year. However, the chemotherapy used in these treatments raises concerns regarding potential infertility, with high costs associated with fertility preservation.

As researchers aim for therapies that do not require chemotherapy, the expectation is that the new gene treatments will initially serve roughly 10% of sickle cell patients. For now, patients are cautiously considering their options, evaluating the risks and benefits of emerging treatments while seeking to maintain their health and fertility as they navigate life with sickle cell disease.