CGTLive's 2024 Pillars of Progress: Top News in Hematology

For all of 2024, our team was following the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2024 has been hematology. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in hematology over the course of 2024.

Here, we'll highlight some of the most-read content on CGTLive's hematology page this year. Click the buttons to read further into these stories.

Canada Approves Vertex and CRISPR Therapeutics’ Gene Therapy Casgevy for Sickle Cell Disease and TDT

“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."
—Kevin Kuo, MD

In September, Health Canada granted marketing authorization to Vertex Pharmaceuticals' and CRISPR Therapeutics’ autologous gene-edited cell therapy exagamglogene autotemcel (exa-cel), marketed under the name Casgevy, for the treatment of sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises (VOCs) and patients aged 12 years and older with transfusion-dependent beta thalassemia (TDT). The approvals were based on data from the phase 1/2/3 CLIMB-121 clinical trial (NCT03745287) and the phase 1/2/3 CLIMB-111 clinical trial (NCT03655678).

Pfizer’s Hemophilia B Gene Therapy Approved as Beqvez in Canada

“Pfizer has more than 30 years of experience in developing and commercializing therapies for hematological disorders, and a deep understanding of the significant challenges that people living with hemophilia continually face. We are proud to introduce an innovative therapy for people living with hemophilia B in the form of gene therapy."
—Frédéric Lavoie

In January, Health Canada approved Pfizer Canada’s gene therapy fidanacogene elaparvovec under the name Beqvez for treating patients with moderately severe to severe hemophilia B with congenital Factor IX (FIX) deficiency who are negative for neutralizing antibodies to variant adeno-associated virus (AAV) serotype Rh74. The approval was based on data from the open label, single arm phase 3 BENEGENE-2 trial (NCT03861273) which met its primary endpoint of demonstrating noninferiority and superiority in annualized bleeding rates (ABR) compared with standard of care FIX therapy in 45 enrolled participants.

Uptake of Nononcology Gene Therapy Remains Slow in Hematology

“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, and more than 40 additional patients already scheduled to initiate the treatment journey for a bluebird gene therapy by the end of this year. We are further encouraged by the commitment to provide patient access across both commercial and government payers, most recently conveyed through multiple positive Medicaid decisions and the growing number of published coverage policies for Lyfgenia, and we expect approximately 85 patient starts across our portfolio this year.”
—Andrew Obenshain, MBA

Patient use of the 2 FDA-approved gene therapy products for sickle cell disease (SCD), Vertex Pharmaceuticals' and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel; marketed as Casgevy) and bluebird bio’s lovotibeglogene autotemcel (lovo-cel; marketed as Lyfgenia), in the commercial setting remained low in the months following approval. Despite the approval of both gene therapy products by the FDA occurring simultaneously on December 8, 2023, as of August 2024 only 4 patients had begun treatment with lovo-cel in the commercial setting, while 20 patients were reported to have begun treatment with exa-cel.

Allogeneic Hematopoietic Stem Cell Transplantation Replicates Posititve Outcomes in Transfusion-Dependent Thalassemia

"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. We aimed to confirm this result and to assess the outcomes of allo-HSCT for TDT patients transplanted with alternative donor. We report excellent 2-year OS and EFS… Allo-HSCT with alternative donors can be considered as a frontline option for TDT patients lacking matched sibling donors. Patients receiving alternative donors will also benefit from an improved GvHD-prophylaxis strategy.”
—Rongrong Liu, MD, and colleagues

Three-year event-free survival data from a phase 4 prospective trial (NCT04009525) in China assessing the validity of a prior study of patients with transfusion-dependent thalassemia (TDT) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) suggest that the approach can be effective, particularly when done with matched sibling donors (MSDs). The data were presented at the 66th American Society of Hematology (ASH) Annual Meeting, held December 7-10, 2024, in San Diego, California.

Patient With Sickle Cell Disease Dies From Complications Related to Busulfan-Conditioning Following Treatment With Beam’s Base-Editing HSC Therapy BEAM-101

“This is a sad outcome and it really underscores the real risks of doing myeloablative transplant with chemotherapy. These risks are well known. This includes significant toxicities that are possible and the rare, but real, risk of mortality.”
—John Evans, MBA

A patient treated for SCD in the context of Beam Therapeutics’ phase 1/2 BEACON clinical trial (NCT05456880), which is evaluating the company’s investigational base-edited autologous hematopoietic stem cell (HSC) therapy BEAM-101, died, according to a November announcement. The patient’s death was deemed by the trial’s investigator to be related to the busulfan-conditioning regimen that patients must receive prior to administration of BEAM-101, rather than to the HSC therapy itself.