Evaluation of Advanced Therapy Medicinal Products by the National Institute for Health and Care Excellence (NICE): An Updated Review

Abstract

This review discusses the methodological challenges to the evaluation of advanced therapy medicinal products (ATMPs) by the UK National Institute for Health and Care Excellence (NICE). We analysed the health technology appraisals (both published and in development) of ATMPs conducted by NICE in England until July 2021. A total of 14 health technology appraisals of ATMPs were included, of which two were in development and 12 had been published. There were ten gene therapy products (talimogene laherparepvec [TA410], strimvelis [HST7], tisagenlecleucel [TA554 and TA567], axicabtagene ciloleucel [TA559], voretigene neparvovec [HST11], autologous anti-CD19-transduced CD3+ cells [TA677], betibeglogene autotemcel [ID968], onasemnogene abeparvovec [HST15] and OTL-200 [ID1666]), one tissue engineered product (holoclar [TA467]) and three somatic cell therapy products (darvadstrocel [TA556] and autologous chondrocyte implantation [ACI][TA477 and TA508]). Only three of these technologies were not recommended by NICE, although four were only recommended within the Cancer Drugs Fund. There was large uncertainty in the assessment of clinical effectiveness, as evidence relied mostly on small, single-arm, open-label studies. There were also several concerns in the cost-effectiveness evaluations, such as limited information on health-related quality of life, immature survival data due to short follow-up, and unclear curative potential. Substantial risk may be incurred with ATMPs, which have high upfront and possibly irrecoverable costs but uncertain long-term benefits. In conclusion, the challenges raised by the economic appraisal of ATMPs, albeit not unique, may be exacerbated by the uncertainty related to the often scant evidence base. Adaptations of the conventional decisionmaking process rather than completely new methods may improve appraisals of ATMPs.

Using automated text classification to explore uncertainty in NICE appraisals for drugs for rare diseases

“…(2) The second hypothesis is that uncertainty paragraphs are more likely to appear in appraisals for RDTs that are classified as ATMPs by the European Medicines Agency compared to non-ATMPs. This is because of uncertainties and limitations in the clinical data and economic evaluations of ATMPs, including trial follow-up periods that are usually too short to observe long-term treatment effects, small sample sizes, and single-arm studies ( 39 ; 40 ).…”

Inborn errors of immunity: A field without frontiers

“…[145][146][147] Indeed, at this point the domains of thalassemia and sickle cell anemia have raised more pharma interest for gene editing approaches. [148][149][150] On another level, for the context of gene therapy or gene editing approaches for IEI, strategies are needed to allow patients affected by ultrarare conditions to benefit from cutting-edge technological advancements in therapeutics. 151 Molecular and cellular therapies have intrinsically high development costs, which are mostly covered by research grants or charity up to the stage of first clinical trials.…”

“…Several gene therapy clinical trials are currently running for X‐linked SCID, RAG1 SCID, ADA‐SCID, Artemis‐SCID, Wiskott‐Aldrich syndrome (WAS), CGD, leukocyte adhesion deficiency type I (LAD I), and Immune dysregulation polyendocrinopathy enteropathy X linked (IPEX) syndrome, while the first gene therapy trials based on gene editing with clustered regularly interspaced short palindromic repeats (CRISPR) instead of viral vector transduction are underway in sickle cell disease and beta thalassemia 145–147 . Indeed, at this point the domains of thalassemia and sickle cell anemia have raised more pharma interest for gene editing approaches 148–150 …”

ATMP development and pre-GMP environment in academia: a safety net for early cell and gene therapy development and manufacturing

“…Over the years, an increasing number of ATMP clinical trials are conducted for treatment of cancer, genetic disorders, cartilage defects and metabolic diseases as they have potential curative outcomes and also a long-lasting therapeutic effect. 4 …”