NEW YORK – Vertex Pharmaceuticals on Friday said that the European Medicines Agency's Committee for Medicinal Products for Human Use has recommended conditional approval of its gene therapy exagamglogene autotemcel (exa-cel) for treating severe sickle cell disease and transfusion-dependent beta thalassemia.
Exa-cel involves using the CRISPR-Cas9 gene editing system to edit a patient's own hematopoietic stem and progenitor cells ex vivo to alter the BCL11A gene and boost fetal hemoglobin levels in red blood cells. CHMP issued the positive recommendation after reviewing data on exa-cel's activity from the Phase III CLIMB-111 and CLIMB-121 trials, as well as long-term follow-up data from the CLIMB-131 trial.
The US Food and Drug Administration also relied on data from these studies to approve exa-cel's sickle cell indication earlier this month, as did regulators in the UK when they approved it for treating sickle cell and beta thalassemia in November. Exa-cel is marketed under the brand name Casgevy in the US.
Vertex, which has headquarters in Boston and London, recently shared an updated analysis at the American Society of Hematology's annual meeting, in which 29 out of 30 sickle cell disease patients who had at least 16 months of follow-up data didn't experience vaso-occlusive crises and didn't need to be hospitalized for at least one year post-treatment. According to another analysis reported at the same meeting, 91 percent of 35 transfusion-dependent beta thalassemia patients with at least 16 months of follow-up data achieved transfusion independence.
"There is an urgent need for new potentially curative treatments in beta thalassemia and sickle cell disease, as people with these diseases still have a shorter life expectancy than the general population and an impaired quality of life," said Franco Locatelli, the principal investigator of the CLIMB-111 and CLIMB-121 studies and a professor of pediatrics at the Catholic University of the Sacred Heart in Rome. "As an investigator, I have witnessed firsthand the transformative impact exa-cel can have on patients' lives, and I eagerly await the approval in the European Union."
The European Commission will review CHMP's recommendation for conditional approval and make a decision by February 2024. The EC grants conditional approvals to drugs that don't yet have comprehensive efficacy and safety evidence but that promise a major therapeutic advantage for patients with a serious or life-threatening condition. Conditional approval is valid for a year and renewable annually, allowing for analysis of the emerging evidence.
If approved, exa-cel would be the only marketed gene therapy for patients in the EU at least 12 years of age with severe sickle cell disease who have recurrent vaso-occlusive crises or for transfusion-dependent beta thalassemia patients who can have hematopoietic stem cell transplantation but for whom a human leukocyte antigen-matched related HSC donor is not available.