Will the high price of gene therapy for sickle cell disease put this cure out of reach?

On December 8, 2023, the U.S. Food and Drug Administration (FDA) approved Casgevy, the first gene therapy utilizing clustered, regularly interspaced short palindromic repeats (CRISPR) for the treatment of sickle cell disease in patients 12 years and older. Mimicking a protective mutation that causes fetal hemoglobin (HbF) to persist into adulthood, Casgevy uses the CRISPR-Cas9 enzyme to edit a patient’s own blood stem cells to intentionally disable a DNA “brake” on HbF production. The modified stem cells are transplanted back to the patient and result in the production of high levels of HbF, preventing the sickling of red blood cells and eliminating or greatly reducing future painful vaso-occlusive (VOC) crises. In an ongoing single-arm trial—initial results were published in 2020—29 out of 31 treated patients had no severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period.

The approval of Casgevy, which has a list price of $2.2 million for the single course of treatment, had been anticipated for months. However, the number of the estimated 100,000 Americans affected with sickle cell disease who will be able to afford it is unclear. Although the lifetime medical costs associated with sickle cell disease average $1.7 million, insurance companies may be unwilling to pay the exceptionally high up-front cost of this curative therapy. Compared with standard of care, one analysis found gene therapy to be an equitable strategy for U.S. patients per distributional cost-effectiveness analysis standards. Obstacles in addition to cost include needing to undergo chemotherapy and being hospitalized for months until the patient’s immune system recovers.

In Africa and India, which are home to most of the world’s population living with sickle cell disease, many patients die in childhood because of lack of access to standard-of-care treatments. For example, hydroxyurea, which reduces the frequency of VOCs and prolongs survival, was approved by the FDA in 1998 but remains unavailable to most patients. Experts recently proposed expanding the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) to provide hydroxyurea therapy for $67 per person to sickle cell patients in sub-Saharan Africa at a total cost of less than $100 million per year. That modest budget would barely begin to meet the needs of those potentially eligible for gene therapy, even if they were able to travel to one of the only three centers for bone marrow transplants in Nigeria, Tanzania, and South Africa.

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This post first appeared on the AFP Community Blog.