Potential lifetime quality of life benefits of choroideremia gene therapy: projections from a clinically informed decision model

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Learning Objectives

Upon completion of this activity, participants will be able to:

  1. 1.

    Describe the estimated lifetime benefit of gene therapy for the retinal dystrophy choroideremia, according to a Markov model of disease progression informed by clinical data of AAV.REP1 and voretigene neparvovec.

  2. 2.

    Illustrate the effects of discount rate and sensitivity analysis on estimated lifetime benefit of gene therapy for choroideremia, according to a Markov model of disease progression informed by clinical data of AAV.REP1 and voretigene neparvovec.

  3. 3.

    Identify clinical implications of the estimated lifetime benefit of gene therapy for choroideremia, according to a Markov model of disease progression informed by clinical data of AAV.REP1 and voretigene neparvovec.

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Credit hours

1.0

Release date: 17 July 2019

Expiration date: 17 July 2020

Post-test link: https://medscape.org/eye/posttest913835

Authors/Editor disclosure information

Sobha Sivaprasad has disclosed the following relevant financial relationships: Served as an advisor or consultant for Allergan, Bayer, Boehringer Ingelheim, Roche, Heidelberg, Optos. Served as a speaker or a member of a speakers bureau for Bayer, Allergan, Novartis, Optos. Received grants for clinical research from: Bayer, Boehringer Ingelheim, Allergan, Novartis, Optos. REM has disclosed the following relevant financial relationships: Served as an advisor or consultant for Nightstar Therapeutics plc; Spark Therapeutics, Inc. Served as a speaker or a member of a speakers bureau for Nightstar Therapeutics plc. Received grants for clinical research from Nightstar Therapeutics plc. CLHH, JKJ, JAS, RPV, and DAB have disclosed no relevant financial relationships.

Journal CME author disclosure information

Laurie Barclay, MD: freelance writer and reviewer. Laurie Barclay, MD, has disclosed no relevant financial relationships.

Abstract

Background

The first gene therapy for an inherited retinal dystrophy recently received market approval in the United States; multiple other gene therapies are in the clinical pipeline. Thus far, gene therapy has commanded prices in the range of $500,000 to over $1,000,000 for the one-time doses and have been indicated for highly orphan diseases where there is no other viable treatment option. To be adopted by healthcare systems, gene therapy will need to show clinical benefit in line with its increased costs. Before longitudinal patient studies are available, model-based estimations will be necessary to project the full clinical benefit of gene therapy.

Methods

To investigate the lifetime benefit of gene therapy for the retinal dystrophy choroideremia, we have built a Markov model of disease progression informed by clinical data of AAV.REP1 and voretigene neparvovec (Luxturna, Spark Therapeutics). Gene therapy patient benefit was estimated by quality-adjusted life years (QALYs) in three hypothetical disease severity patient groups. The severity of disease was defined by the combined effect of remaining retinal area and visual acuity and assigned corresponding health utility values.

Results

Early-stage patients treated with gene therapy were estimated to gain, in average, 14.30 QALYs over standard-of-care, mid-stage patients 6.22 QALYs, and late-stage patients 1.48 QALYs over untreated patients during their lifetime owing to treatment. Cost-effectiveness was not assessed as AAV.REP1 is still in clinical trials.

Conclusions

In young adults in the earlier stages of choroideremia, successful gene therapy is expected to provide a significant increase in health-related quality of life.

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Acknowledgements

CLHH thanks the SENS Research Foundation for their continued intellectual support. CLHH is funded by the NIHR. JKJ is funded by the National Institute for Health Research (NIHR). JS is funded primarily by an MRC UK DPhil Studentship. DB gratefully acknowledges personal funding from the Oxford Musculoskeletal National Institute for Health Research Biomedical Research Unit (NIHR BRU), the Saïd Foundation and the SENS Research Foundation. REM receives funding from the Oxford University Hospitals NHS Foundation Trust NIHR Biomedical Research Centre (BRC). CLHH has been a consultant for multiple life sciences companies and biotechnology investment firms. DB is a stockholder in Translation Ventures Ltd. (Charlbury, UK) and IP Asset Ventures Ltd. and Biolacuna Ltd., companies that among other services provide biomanufacturing, regulatory, and financial advice to pharmaceutical clients. DB also is subject to the CFA Institute’s codes, standards, and guidelines, so he must stress that this piece is provided for academic interest only and must not be construed in any way as an investment recommendation. In addition, at time of publication, DB and the organizations with which he is affiliated may or may not have agreed to and/or pending funding commitments from the organizations named herein. REM is a Founder of Nightstar Therapeutics Inc and a consultant to Spark Therapeutics Inc. REM is acting as an independent academic and neither Nightstar nor Spark had any role in the conception or execution of this research study. CLHH is not funded by Nightstar Therapeutics, Spark Therapeutics, or any other entity with commercial interest in gene therapy.

Author information

CLHH: developed model and wrote manuscript. JKJ: choroideremia expertize. JS: reviewed for clarity and accessibility to a diverse audience. RPV: supervised and validated model development. DAB: copyediting. REM: choroideremia expertize and general academic support.

Correspondence to Rafael Pinedo-Villanueva.

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Conflict of interest

REM is a Founder of Nightstar Ltd and a consultant to Spark Therapeutics Inc. REM is acting as an independent academic and neither Nightstar nor Spark had any role in the conception or execution of this research study. CLHH does not receive funding or other incentives from NightStar, Spark Therapeutics, or any other entity with commercial interests in Choroideremia gene therapy. JKJ, JAS, RPV and DAB have no conflicts.

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Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Co-senior authors: Rafael Pinedo-Villanueva, David A. Brindley, Robert E. MacLaren

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