Just over two years after the approval of the first gene therapies for sickle cell disease, Casgevy from Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia from Genetix Bio (formerly bluebird bio), uptake remains limited despite initial optimism.
At the time of their FDA approvals, experts raised concerns about patient access. “The numbers of people who can be treated are limited,” said Eric Kmiec, founder and executive director of the ChristianaCare Gene Editing Institute. “We must work with the health care industry and pharmaceutical companies who will market, produce and deliver the treatments to make sure that all people can get access.”
According to Vertex’s 2025 earnings report, only 64 patients received infusions of Casgevy last year for sickle cell disease or transfusion-dependent beta thalassemia, with an additional 147 undergoing initial cell collection. Genetix Bio reported treating just over 100 patients with Lyfgenia. Both companies have plans to increase these numbers.
Vertex generated $116 million in revenue from Casgevy in 2025 and expects combined sales from Casgevy and pain medication Journavx to reach $500 million this year—a projected increase of 185%. Whether these targets will be met is uncertain.
Courtney Rice, principal at Acadia Strategy Partners, identified several barriers affecting adoption rates. “You’re asking a lot of time for these patients to be out of the game, both from the conditioning time to the procedure to the engraftment,” Rice said. She noted that this aspect was overlooked during initial celebrations.
Sickle cell disease affects about 100,000 Americans—over 90% are Black—and results from a genetic mutation impacting hemoglobin production. Tim Hunt, CEO of the Alliance for Regenerative Medicine, called Casgevy’s approval “a seminal moment in the history of biotechnology and human health.”
Despite broad reimbursement for Lyfgenia being available, most eligible patients remain untreated. A Genetix executive stated: “However, despite broad reimbursement already in place, the vast majority of patients have not been treated.”
A major obstacle is the required conditioning regimen using busulfan chemotherapy before infusion with either therapy. This process destroys defective blood stem cells but also poses significant risks including infertility due to its impact on rapidly dividing cells like ovarian tissue. Rice described it as: “That conditioning regimen is gnarly at best.” Cantor Fitzgerald highlighted concerns within the sickle cell community regarding sterility: “Sterility is a hot button issue in the SCD community,” adding that younger patients cannot always preserve fertility through sperm or egg banking.
Victoria Gray—the first person treated with Casgevy—said avoiding such regimens could improve access: in vivo gene therapy might allow more patients treatment without chemotherapy agents.
Tessera Therapeutics is working on an in vivo gene writer targeting sickle cell mutations directly; it secured a $50 million investment from The Bill & Melinda Gates Foundation for this project in December 2024.
Other factors hindering uptake include lengthy treatment timelines which disproportionately affect those healthy enough—and likely employed—to qualify for therapy. Even when matched donors are available for alternative treatments like hematopoietic stem cell transplantation (HSCT), many decline due to harsh pre-treatment regimens; only about 1-2% receive HSCT out of roughly 15% who have sibling matches among U.S. SCD patients.
Gray also cited insufficient provider education as a limiting factor: “When [patients] go in and ask about Casgevy, gene therapy, Lyfgenia, they’re being discouraged by medical providers... Until doctors that see patients on a regular basis are educated there are going to be so many gaps.”
These challenges contributed to bluebird bio’s decision last year to sell itself for $30 million amid financial difficulties—a move intended as a lifeline before rebranding as Genetix Biotherapeutics and announcing plans to expand manufacturing capacity.
Commercial demand has since increased significantly according to Genetix executives: “We expect rapid demand and growth for Lyfgenia in 2026 and beyond.” For Casgevy too there are signs of growth; half its total infusions last year occurred during Q4 alone according to Vertex’s latest earnings call. The company plans soon to seek approval for use in children aged five through eleven—a move expected under expedited review thanks to a Commissioner’s National Priority Review Voucher.
Still some analysts remain cautious about future adoption trends; Rice suggested initial interest may wane now that early demand has been met: “We’ve probably burned through that bolus.”
