Gene Therapy and Sickle Cell Disease: Patients’ Perspectives

By Deena Beasley
LOS ANGELES (Reuters)

Student Zoe Davis, 20, was just weeks into her junior year when she landed back in the hospital with severe sickle cell pain earlier this month. She is doing what she can to prevent the crippling attacks in her arms, legs, and abdomen that are becoming more frequent.

She knows new gene therapies may provide long-term relief to some of the 100,000 Americans who suffer from sickle cell disease. But she’s holding off trying one.

“It is so new … I wanted to see more success stories before I committed to it,” said Davis, who is studying veterinary science at North Carolina Agricultural and Technical State University in Greensboro.

Her hesitation illustrates a common reason why the take-up for potentially life-changing treatments, which cost between $2 million and $3 million in the U.S., is proving even slower than expected, according to interviews with specialists and patients.

Younger patients—who weigh school schedules and are reluctant to add more medical burden—have been less enthusiastic than predicted, said Dr. Leo Wang, a hematologist-oncologist at City of Hope Children’s Cancer Center near Los Angeles.

“Some kids are just not interested,” he said, noting that while patients ages 20 to 40 are more open, some have such severe disease that they are not good candidates.

The new one-time treatments, approved in the U.S. last December, have so far been used on around 100 people globally, including in clinical trials. They require chemotherapy, which raises the risk of cancer and can also cause infertility.

Some patients say the time involved—up to a year—is a daunting prospect for anyone whose condition is not critical.

Worldwide, 8 million people are estimated to have sickle cell disease, according to the National Institutes of Health. Most affected individuals in the U.S. are Black. The illness causes red blood cells to form an abnormal “sickle” shape that can block blood flow, leading to excruciating pain, strokes, organ damage, and premature death. The mutation that causes sickle cell disease is prevalent in malaria-endemic areas, providing some protection against malaria infection.

As of September, at least 30 people worldwide had begun gene therapy outside of trials, according to the drugmakers whose therapies were approved in America. Both treatments involve a lengthy process to remove a patient’s bone marrow stem cells, genetically modify them in a lab, administer chemotherapy, and monitor the individual post-infusion.

Doctors anticipate increased therapy use as more safety and efficacy data emerges, but many patients remain on the sidelines, balancing pregnancies, considering the costs of fertility treatments, or put off by the lengthy process and insurance approval requirements. Others with manageable disease are also not eligible for treatment.

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

Treatment Landscape

According to experts, more than 80% of U.S. patients are not eligible for the new therapies. Bluebird Bio cut its forecast for usage of its gene therapy products this year to a maximum of 85 from 105. Vertex Pharmaceuticals reported that 20 patients worldwide have started its treatment process.

While some gene therapies have reached blockbuster sales, uptake of sickle cell therapies is expected to be slow, mainly used for those with the most severe disease.

Debilitating sickle cell pains strike any part of the body and can last from a few hours to several weeks. Existing treatments include blood transfusions and the generic drug hydroxyurea, which helps normalize red blood cell shape. Pfizer recently withdrew its sickle cell treatment, Oxbryta, due to risks of complications.

Gene therapies require careful consideration of risks against potential benefits. Experts note that the therapies might be recommended only for severe cases, questioning the logic of offering a new gene therapy to those whose current treatment is sufficient.

Doctors also highlight fertility risks associated with chemotherapy. Costs for egg freezing and sperm banking can be significant, and many patients depend on insurance coverage that may not always extend to these options.

Sickle cell patient Dominique Goodson, pregnant with her first child, is interested in receiving gene therapy after childbirth but must ensure she can preserve fertility for future children.

Both Vertex and Bluebird provide programs to help with fertility service payments, though these may not be available to patients on Medicaid, which covers over half of U.S. sickle cell patients. Medicaid has proposed a pilot program for fertility services but is also engaged in a legal dispute with Vertex.

Both Vertex and Bluebird’s therapies show promise, with trial data suggesting significant pain crisis reductions post-treatment. However, the practical aspects of cost, eligibility and patient readiness remain critical challenges for broader adoption of these advances in sickle cell management.