The landscape of hematological gene therapy saw significant regulatory progress in 2024, though adoption rates and safety concerns continue to present challenges for the field.
Health Canada made history by approving two major gene therapies: Vertex and CRISPR Therapeutics' Casgevy (exagamglogene autotemcel) for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), as well as Pfizer's Beqvez (fidanacogene elaparvovec) for hemophilia B.
Commercial Adoption Lags Behind Regulatory Success
Despite the regulatory momentum, patient uptake of approved gene therapies has been notably slow. For SCD treatments approved by the FDA in December 2023, only 24 patients had begun treatment by August 2024 - 20 with Vertex/CRISPR's Casgevy and 4 with bluebird bio's Lyfgenia (lovotibeglogene autotemcel).
Andrew Obenshain, MBA, of bluebird bio, reported some progress in commercial rollout: "We are seeing clear evidence that our commercial launch is accelerating, with over 20 cell collections completed in SCD and TDT to date in 2024." The company projects approximately 85 patient starts across their portfolio this year.
Safety Concerns Persist
The field faced a sobering reminder of treatment risks when a patient in Beam Therapeutics' BEACON trial for BEAM-101, a base-edited autologous hematopoietic stem cell therapy, died from complications related to busulfan conditioning.
"This is a sad outcome and it really underscores the real risks of doing myeloablative transplant with chemotherapy," noted John Evans, MBA. "These risks are well known. This includes significant toxicities that are possible and the rare, but real, risk of mortality."
Traditional Transplant Approaches Show Promise
While gene therapy development continues, traditional allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated encouraging results in TDT patients. A phase 4 trial in China showed particularly strong outcomes with matched sibling donors.
Dr. Rongrong Liu and colleagues reported, "We had reported an encouraging outcome of allo-HSCT in a single center study, which the 3-year [EFS] was 97% in patients with TDT transplanted with HLA-matched sibling donors."
Market Access and Coverage Expanding
Progress is being made in expanding access to these innovative therapies. Multiple positive Medicaid decisions and increasing numbers of published coverage policies suggest growing payer acceptance. However, the complex nature of gene therapy administration and high treatment costs continue to influence adoption rates.
The approval of Casgevy in Canada was particularly significant for the field. As Dr. Kevin Kuo noted, "Casgevy's approval is an exciting moment for 2 patient communities that have long awaited an innovative therapy that brings new hope and possibilities for those in need."
