NEW YORK – The National Institute for Health and Care Excellence has recommended Vertex Pharmaceuticals' Casgevy (exagamglogene autotemcel; exa-cel) be made available to patients in England with transfusion-dependent beta thalassemia (TDT) through the Innovative Medicines Fund.
In a final draft decision published on Thursday, NICE said TDT patients at least 12 years old who are able to have a stem cell transplant but don't have a donor will be eligible to receive the CRISPR-based gene therapy through the IMF, so that the institute can collect more data on its clinical efficacy and cost effectiveness.
Casgevy received conditional marketing authorization from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for TDT and sickle cell disease (SCD) in November 2023. When it came to Casgevy's sickle cell disease indication, NICE in March declined to recommend the treatment in a draft guidance, wanting to see more data. "Vertex continues to work collaboratively with NICE and National Health Service England to ensure eligible sickle cell disease patients in England can also access this treatment as soon as possible," the company said in a statement, adding that it is in similar discussions with reimbursement authorities in the EU, as well.
In recommending the TDT indication, NICE reviewed data from the CLIMB-THAL-111 single-arm trial, in which nearly 93 percent of patients achieved transfusion independence for at least a year. But NICE flagged uncertainties in the clinical evidence, such as the ability of the gene therapy to improve outcomes over the long term and the lack of a comparator arm showing Casgevy's ability to reduce the need for transfusions compared to standard interventions.
Vertex's economic modeling was also limited by these gaps in clinical evidence. Casgevy has a list price of £1,651,000.00 ($2,095,337.21), but Vertex is providing it to the NHS at an undisclosed discount.
"Although there are some uncertainties in the evidence for its long-term benefits, the committee felt exa-cel could represent a potential cure for some people with transfusion-dependent beta-thalassemia, freeing them from the burden and risks of needing regular blood transfusions," Helen Knight, director of medicines evaluation at NICE, said in a statement.
TDT is a genetic blood disorder in which patients can't produce enough hemoglobin, the protein that carries oxygen throughout the body. Casgevy, which Vertex developed with CRISPR Therapeutics, addresses this through ex vivo editing of the BCL11A gene in patients' own CD34-positive hematopoietic stem and progenitor cells with CRISPR-Cas9. The edited genes are designed to increase production of fetal hemoglobin, which, like the adult version, facilitates oxygen delivery.
Beta-thalassemia affects mainly people with Pakistani, Indian, or Bangladeshi ethnicity in the UK and can delay growth, cause bone problems, hinder endocrine development, and diminish patients' life span, and patients with the most severe form of the disease need regular blood transfusions. NICE estimated that in England there are around 460 TDT patients who will be eligible to receive Casgevy through the IMF.
"Today's final draft guidance also addresses our aim of reducing health inequalities associated with conditions like transfusion-dependent beta-thalassemia," Knight added. "In doing so it demonstrates our ability to address these issues proportionately and flexibly as part of our standard process, ensuring access to innovative, effective treatments that provide value for money for taxpayers and the NHS."
The US Food and Drug Administration approved Casgevy's TDT indication in January and the SCD indication in December.