Busulfan

iStock, BrianAJackson The first gene therapies approved to treat sickle cell disease in December 2023 are struggling on the market. But there are glimpses of forward momentum as Vertex and Genetix Bio provide updates. Just over two years ago, Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy and bluebird bio’s Lyfgenia won FDA approval as the first gene therapies for sickle cell disease. It was hailed as a watershed moment for patients with the debilitating blood disorder, but even then, there were concerns about access to treatment. “The numbers of people who can be treated are limited,” Eric Kmiec, founder and executive director of the ChristianaCare Gene Editing Institute, said in a statement to BioSpace the day of the approvals. “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.” Fast-forward two years and Kmiec’s warning has come to pass. Last year, just 64 patients with sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT)—for which Casgevy was greenlit in January 2024—received infusions of the gene therapy, according to Vertex’s full-year 2025 earnings report . An additional 147 people had their first cell collection. Meanwhile, Genetix Bio— formerly bluebird bio —has treated over 100 patients with Lyfgenia, which is only approved for SCD, a member of Genetix’s executive team told BioSpace in an email. But both companies are aiming for more, of course. In 2025, Vertex earned $116 million in revenue from Casgevy. The company expects the gene therapy—along with recently approved pain medication Journavx—will combine to bring in $500 million this year, a 185% increase over 2025. Whether Vertex will hit those numbers remains to be seen. Courtney Rice, principal at Acadia Strategy Partners, pointed to potential reasons for the seemingly lackluster launch that could continue to challenge growth. “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 of the new gene therapies. “And that somehow sort of got glossed over in the parade, in the champagne shaking and excitement.” Barriers to Uptake Approximately 100,000 Americans suffer from sickle cell disease, which is caused by a mutation in the genes involved in producing hemoglobin’s beta subunit, an iron-rich compound found in red blood cells (RBC). This results in some of the cells being shaped like “sickles,” slowing or blocking blood flow and leading to anemia and episodes of extreme pain. More than 90% of patients are Black. In a statement to BioSpace in December 2023, Tim Hunt, CEO of the Alliance for Regenerative Medicine, called the approval of Casgevy, the first-ever CRISPR-based gene editing therapy, “a seminal moment in the history of biotechnology and human health.” The Genetix executive emphasized that tens of thousands of patients with SCD could benefit from Lyfgenia. “However, despite broad reimbursement already in place, the vast majority of patients have not been treated.” For Rice, the harsh conditioning regimen is the primary impediment to uptake of the gene therapies. Both Casgevy and Lyfgenia require patients to be treated with a conditioning regimen called busulfan, a chemotherapy drug used to prepare the bone marrow for the infusion of the gene therapies. Busulfan is used prior to the infusion of Casgevy and Lyfgenia to destroy the defective blood stems in the bone marrow to make way for the edited cells. “That conditioning regimen is gnarly at best,” Rice said. For Victoria Gray, a patient advocate and the first person with SCD to be treated with Casgevy, this conditioning regimen was the most challenging part of the process. Gray told BioSpace that in vivo gene therapy could open up access to more patients because it negates the need for these chemotherapeutic agents. Genetic editing biotech Tessera Therapeutics is developing an in vivo gene writer for SCD, aiming to directly correct the mutation that causes cells to sickle. The company received a $50 million investment from the Bill & Melinda Gates Foundation for the program in December 2024. Another barrier to access for the current gene therapies, Rice noted, is that busulfan comes with a high risk of infertility. In addition to destroying the defective blood stem cells in the bone marrow to make way for the edited cells, the toxic treatment wipes out other rapidly dividing cells, including ovarian cells that develop into eggs. “Sterility is a hot button issue in the SCD community,” Cantor Fitzgerald noted in its presentation. “Younger (pre-pubescent) patients who are most appropriate for cell transplantation are not able to prevent infertility through sperm or egg cell banking.” Meanwhile, the extensive time requirement involved in treatment with Casgevy and Lyfgenia is somewhat of a catch-22, according to Rice, who noted that people who are healthy enough to be eligible “are probably in the working population and commercially insured.” Rice recalled a conversation with a colleague about another potentially curative SCD treatment: hematopoietic stem cell transplantation (HSCT), which, unlike the approved gene therapies, requires a human leukocyte antigen (HLA)–identical sibling donor. Her colleague explained that patients are reluctant to receive a transplantation even when there is an HLA match identified because of the conditioning regimen. A 2023 presentation by Cantor Fitzgerald shared with BioSpace showed that of the approximately 100,000 patients with SCD, around 15,000 have an HLA-matched sibling donor, but only between 1,000 and 2,000 are treated with HSCT. Rice recalled her colleague posing a poignant question about Casgevy and Lyfgenia: “What makes you think that because [SCD treatment is] now open to all people . . . that the uptake would be higher?” Gene therapy In Vivo Is Having a Moment as Cell and Gene Therapy Sector Gathers in San Diego A recurring theme Tuesday morning at Phacilitate’s Advanced Therapies Week was the quickly emerging potential of in vivo approaches to cell and gene therapy—a trend also reflected in recent investments by Eli Lilly and Regeneron. February 11, 2026 · 4 min read · Heather McKenzie Finally, Gray pointed to a lack of prescriber knowledge as stunting the launches of Casgevy and Lyfgenia. “When [patients] go in and ask about Casgevy, gene therapy, Lyfgenia, they’re being discouraged by medical providers, and it’s not surprising to me because I’ve been there,” she said during her presentation. “Until the doctors that see patients on a regular basis are educated, there are going to be so many gaps.” Upward Momentum These barriers and others involved with these complex treatments—such as manufacturing issues and a challenging return-on-investment proposition—made it impossible for bluebird to survive as a public company. Bluebird bio sold itself to two global investment firms, Carlyle and SK Capital Partners, in February last year for $30 million—a troubling smoke signal sent out by one of gene therapy’s pioneers. Unable to successfully market its groundbreaking products, the biotech was running out of money, and the go-private deal was a lifeboat. Then in September 2025, the company reverted to its roots, assuming its original moniker of Genetix Biotherapeutics . Genetix at that time also revealed some of its strategy to revive the company. This included plans “to substantially increase our manufacturing capacity within the next year to meet growing demand,” according to a Sept. 18 press release . Bankruptcy Bluebird’s Go-Private Deal Highlights Fraught Life Preserver for Struggling Biotechs Facing declining valuations and funding challenges, public biotechs like bluebird bio are going private to restructure, reduce regulatory burdens and refocus on long-term growth. March 12, 2025 · 6 min read · Ana Mulero Indeed, commercial demand for Lyfgenia “has surged significantly,” the Genetix executive said. “We expect rapid demand and growth for Lyfgenia in 2026 and beyond,” the company executive said. Casgevy also appears to be trending upward. Thirty of the 64 patients infused with Vertex and CRISPR’s product received those infusions during the fourth quarter of 2025, Vertex noted in its 2025 earnings report. And the company plans to approval of Casgevy in children aged 5 to 11 in the first half of this year, CEO Reshma Kewalramani said on a Feb. 12 earnings call. Vertex received a Commissioner’s National Priority Review Voucher for Casgevy and expects a quick review for the label expansion. Rice was less optimistic, predicting that the uptake of Casgevy and Lyfgenia will actually decrease. “I tracked both of those launches, and leading up to it, we had this bolus. People [were] waiting in line.” Now, she said, “We’ve probably burned through that bolus.” .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });