Strimvelis® for Treating Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency: An Evidence Review Group Perspective of a NICE Highly Specialised Technology Evaluation

Abstract

The Centre for Reviews and Dissemination and Centre for Health Economics Technology Assessment Group at the University of York was commissioned by the National Institute for Health and Care Excellence (NICE) Highly Specialised Technologies (HST) programme to act as the independent Evidence Review Group (ERG) for an appraisal of Strimvelis ® , a gene therapy treatment for adenosine deaminase deficiency–severe combined immunodeficiency (ADA-SCID). This paper describes the manufacturing company’s submission of clinical and economic evidence, the ERG’s review and the resulting NICE guidance. For Strimvelis ® compared with haematopoietic stem cell transplant (HSCT) from a matched unrelated donor (MUD) and HSCT from a haploidentical donor, the company base-case deterministic incremental cost-effectiveness ratios (ICERs) were £36,360 and £14,645 per quality-adjusted life-year (QALY) gained, respectively (using a discount rate of 1.5%). Although overall survival in patients receiving Strimvelis ® was substantially higher than historical comparator data on HSCT from a MUD or haploidentical donor, the ERG was concerned that the estimated treatment benefit remained highly uncertain. The ERG critiqued some assumptions in the cost-effectiveness model, including that all patients return to general population mortality and morbidity after a successful procedure; that all patients receive a matched sibling donor following an unsuccessful engraftment; and that differences in wait times exist between the treatments. Incorporating a number of changes to the model, the ERG’s base-case ICERs were £86,815 per QALY gained for Strimvelis ® compared with HSCT from a MUD and £16,704 per QALY gained compared with HSCT from a haploidentical donor (using a discount rate of 1.5%). The ICER for Strimvelis ® compared with HSCT from a MUD was highly sensitive to the difference in procedural mortality and could exceed NICE’s £100,000 per QALY gained threshold for HSTs, if HSCT survival rates have improved since the most recent data. The evaluation committee concluded that the most plausible ICERs were lower than £100,000 per QALY gained and that Strimvelis ® should be recommended for treatment of ADA-SCID where a matched related donor is unavailable.

A systematic review of economic evaluations of advanced therapy medicinal products

“…The cost effectiveness of Strimvelis was examined in 2 analyses, of which 1 was deemed to be cost effective. South et al (2018) 32 reported a NICE Highly Specialised Technology Evaluation which estimated the most plausible ICERs for Strimvelis to be lower than £100 000 per QALY gained. NICE approved Strimvelis for the treatment of adenosine deaminase severe combined immunodeficiency, where a matched related donor is unavailable 31 .…”

“…However, many were incomplete with respect to important methodological detail. The perspective was unclear in 7 of the studies 15,16,24,26,28,31,32 . Two studies 15,16 did not state explicitly the modelling approach.…”

“…The perspective was unclear in 7 of the studies. 15,16,24,26,28,31,32 Two studies 15,16 did not state explicitly the modelling approach. Three studies 24,27,28 did not mention explicitly a time horizon.…”

The Limitless Future of RNA Therapeutics

“…The CD34 + cells are then transduced with a gammaretrovirus vector carrying the gene for human adenosine deaminase (ADA), then reinfused into the patient. These cells home to the patient’s bone marrow where CD34 + cells replicate and generate normal ADA protein to correct the deficiency ( South et al, 2018 ). Zyntelgo was approved in Europe in 2019 for the treatment of beta-thalassemia.…”

Layer-by-Layer technique as a versatile tool for gene delivery applications

“…Among 6000 phenotypes of genetic disorders with known molecular basis that have been identified to date, the hematological diseases became the first successful cases for the development of gene therapy products. Thus, Strimvelis was approved by EMA in 2016 for clinical use in children with adenosine deaminase deficiency [139]. With the invention of robust genome-editing tools, this approach became more and more attractive.…”