A gene therapy for patients with transfusion-dependent beta thalassemia (TDT) didn’t fare well after a thorough review by the United Kingdom’s National Institute for Health and Care Excellence (NICE) turned down biotech firm bluebird bio’s Zynteglo (betibeglogene autotemcel; beti-cel). As it turns out, the UK research agency declared that the clinical trials involved with the Zynteglo investigation were considerably “small” while trial participants were not monitored for sufficient periods of time. Although the British research agency did acknowledge that perhaps at some point those patients treated with the gene therapy may not require blood transfusions, or at least need them not as frequently.
What is transfusion-dependent beta thalassemia (TDT)?
A hereditary disease triggered by a genetic mutation in the β-globin gene with severe consequences. The acute type of the disease is characterized by severe anemia. According to Health Europa, approximately 1.5% of the global population actually are β-thalassemia carriers while 60,000 symptomatic individuals are born per year. The disease, although quite rare, is more prevalent in the Mediterranean, in nations such as Italy, where over 6,500 cases are reported per annum. Those that suffer from this condition completely rely on blood transfusions to maintain hemoglobin levels for the duration of life.
In TrialSite’s “Family Man’s Battle Against the Forefront of Capitalist Medicine: The Case of Errant Gene Therapeutics,” we profiled an Italian American father’s struggle to cure his son and the legal battles and alleged unethical behavior he encountered when dealing with bluebird bio. At least part of that case was recently settled in New York with Memorial Sloan Kettering.
Euro Approval in 2019
The one-off gene therapy was in fact authorized by the European Medicines Agency (EMA) in June 2019. Those patients 12 and older with transfusion-dependent beta thalassemia (TDT) and for whom hematopoietic stem cell (HSC) transplantation is deemed acceptable however a human leukocyte antigen (HLA)-matched related HSC donor isn’t accessible.
While a Phase 1/2 clinical trial in 24 TDT patients with non-beta0/beta0 genotypes, 83% achieved transfusion independence (TI). Even of the remaining patients, two achieved the secondary endpoint of transfusion reduction while another two turned out transfusion dependent.
High Cost and Questionable Value
The cost of just one-off infusion of this gene therapy equals £1.45 million (just over $2 million) although the U.S.-based company purportedly has entered into some form of discounts should NICE approve of the treatment. But NICE ultimately came to the conclusion that the overall cost-effectiveness of this therapy is highly questionable—the price points and value proposition was certainly off from what the agency considered in the realm of acceptability.
Nicola Redfern, manager of bluebird bio in the UK, expressed great concern with the finding: “We are shocked and disappointed by this recommendation and strongly believe that NICE has failed to act in the best interest of people with TDT and their families in England and Wales.”
Ms. Redfern continued that the British agency was disregarding patient, advocacy group and clinician testimony.
Call to Action: Note that the NICE draft guidance for this gene therapy remains open for consultation until March 4, 2021.