Late in 2023 the U.S. Food and Drug Administration (FDA) approved a pair of new therapies that represented a significant scientific breakthrough in gene therapy to treat patients with sickle cell disease (SCD), a rare condition with historically few viable treatment options. 


SCD is linked to an abnormality in the hemoglobin protein, which normally helps carry oxygen throughout the body via red blood cells. This causes red blood cells, normally disc shaped and flexible enough to travel smoothly in the body, to become rigid and misshapen to resemble a “C” or sickle. The resulting symptoms include anemia, swelling of the extremities (hand and feet), frequent infections, vision problems, stroke, and very severe pain in the chest, abdomen, and joints. Patients may also experience severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs) – an accumulation of these events can result in physical disabilities and even death. The majority of SCD cases in the U.S. are seen in people who are of African Ancestry or identify themselves as Black.


On December 8, 2023, the FDA approved Casgevy™ (Vertex Pharmaceuticals Inc.) and Lyfgenia™ (Bluebird Bio Inc.) both innovative cell-based gene therapies. They are developed from the patients’ own blood stem cells, which are removed and genetically modified, then transplanted back as a one-time, single-dose infusion. 


Casgevy, which is now indicated for the treatment of SCD patients 12 years of age and older with recurrent VOCs, is the first FDA-approved therapy developed with a type of genome editing technology known as CRISPR/Cas9. Lyfgenia, which is approved for the treatment of patients 12 years of age and older with SCD and a history of VOEs, employs a lentiviral vector to deliver the modified genetic material. 


A recent article published on May 6, 2024  in The New York Times tells the story of the first patient to begin treatment with one of these gene therapies, a 12-year-old boy from the suburbs of Washington, D.C. who has been living with the painful and debilitating effects of SCD. The piece features the young patient and his families’ experiences,  including the severe physical toll of the disease and its profound impact on quality of life.


The article will be enlightening to those unfamiliar with the complex, multi-step, and months-long process necessary to successfully administer this type of therapy – the featured patient has recently begun this process.


The piece also covers the practical challenges of capacity, such as medical centers’ ability to handle more than a small number of gene therapy patients and laboratory wherewithal to treat large numbers of patient stem cells. For instance, Bluebird estimates that it can treat the cells of approximately 85 to 105 patients per year with Lyfgenia. It should be noted that included in this number are eligible SCD patients, plus others with conditions such as beta thalassemia. 


The question of cost also weighs heavily, as Lyfgenia is estimated to come with a $3.1 million price tag. While the family featured in the article were pleased to report that treatment was covered by their family’s insurance, questions of reimbursement for what is one of the most expensive therapies on the market remain.


Lastly, the story provides a snapshot of the everyday struggles, sacrifices, and hopes of a family looking to relieve their son from a life of acute pain and allow him to live his best life. 


Source: The New York Times, May 6, 2024