, Volume 36, Issue 7, pp 759–768 | Cite as

Ponatinib for Treating Acute Lymphoblastic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

  • Matt Stevenson
  • Abdullah Pandor
  • Jean Hamilton
  • John Stevens
  • Clare Rowntree
  • Marrissa Martyn-St James
  • Andrew Rawdin
  • Ruth Wong
Review Article


As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig®) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG). This article presents the critical review of the company’s submission by the ERG and the outcome of the NICE guidance. The clinical-effectiveness evidence in the company’s submission was derived from a phase II, single-arm, open-label, non-comparative study. Given the lack of comparative evidence, a naïve indirect comparison was performed against re-induction chemotherapy comparing major cytogenetic response and complete remission. Best supportive care (BSC) was assumed to produce no disease response. Despite the limited evidence and potential for biases, this study demonstrated that ponatinib was likely to be an effective treatment for patients with Ph+ ALL. The company submitted a state transition model that analysed the incremental cost effectiveness of ponatinib versus re-induction therapy and BSC for the treatment of Ph+ ALL in patients whose disease is resistant to dasatinib, who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate or who have the threonine-315-isoleucine mutation. This population was further subdivided into those who were suitable for allogeneic stem cell transplant (allo-SCT) and those who were not. The company’s revised economic evaluation, following the clarification process, estimated incremental cost-effectiveness ratios (ICERs) in those suitable for allo-SCT of £31,123 per quality-adjusted life-year (QALY) gained for ponatinib compared with re-induction chemotherapy and £26,624 per QALY gained compared with BSC. For those for whom allo-SCT was unsuitable, the company-estimated ICER compared with BSC was £33,954 per QALY gained. Following a critique of the model, the ERG undertook exploratory analyses that, when combined, produced a range in ICERs (due to uncertainty of the most appropriate overall survival function) of dominant (being less expensive and providing more QALYs) to £11,727 per QALY gained compared with re-induction chemotherapy and between £7892 and £31,696 per QALY gained compared with BSC for those in whom allo-SCT was suitable. For those in whom allo-SCT was not suitable, the ERG estimated that ponatinib was dominant. During the consultation period, the company agreed a revised patient access scheme (PAS) that reduced the ICER ranges to £7156 to £29,995 per QALY gained versus BSC and to less than £5000 per QALY gained versus re-induction chemotherapy. In people for whom allo-SCT was unsuitable, ponatinib dominated BSC. The NICE appraisal committee concluded that ponatinib is a cost-effective use of UK NHS resources in the considered population, subject to the company providing the agreed discount in the PAS.



This summary of the ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. Any errors are the responsibility of the authors.

Author Contributions

Matt Stevenson and Andrew Rawdin critiqued the mathematical model provided and the cost-effectiveness analyses submitted by the company. Abdullah Pandor and Marrissa Martyn-St James critiqued the clinical-effectiveness data reported by the company. Jean Hamilton and John Stevens critiqued the statistical aspects of the submission and the analyses performed by the company. Ruth Wong critiqued the literature searches undertaken by the company. Clare Rowntree provided clinical advice to the ERG throughout the project. All authors were involved in drafting and commenting on the final document. Matt Stevenson acts as the guarantor of the manuscript. This summary has not been externally reviewed by PharmacoEconomics.


This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Project Number 16/51/11). Visit the HTA programme website for further project information (

Compliance with Ethical Standards

Conflict of interest

Dr Clare Rowntree undertook some consulting work in 2015–2016 for ARIAD Pharmaceuticals, the manufacturer of ponatinib. This work resulted in an authored published abstract in a health economics journal. MS, AP, JH, JS, MMSJ, AR, RW have no conflicts of interest to declare.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Health and Related Research (ScHARR)University of SheffieldSheffieldUK
  2. 2.University Hospital of WalesCardiffUK

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