A landscape analysis and discussion of value of gene therapies for sickle cell disease

ABSTRACT

Introduction

Sickle cell disease (SCD) is a rare genetic disease with limited therapeutic options. Gene-based therapies are being investigated in clinical trials to evaluate their curative potential. The expected life-long benefits of one-time administration of genetically corrected stem cells present uncharted challenges in estimating value of these treatments. Our objective is to conduct a landscape analysis of clinical trials and prompt a discussion estimating the value of gene therapy as a therapeutic option for SCD.

Areas covered

We searched Clinicaltrials.gov to identify and characterize clinical trials in gene therapies for SCD. We report available results and discuss current concerns and elements of value necessary to consider as these products come to market.

Expert opinion

Gene therapies could represent a major advance in SCD treatment. Although clinical trials are ongoing, reports of serious adverse events have led to pause of these trials, emphasizing the need to prove long-term tolerability. Measured using the methods of health economic evaluation, we anticipate high up-front costs may be offset by potential life-long benefits of these treatments. During development and after treatment approval, attention should be focused on ensuring adequate availability and equitable access to emerging therapies in underserved areas and low-middle-income countries (LMIC).

KEYWORDS:

• sickle cell disease
• hematopoietic stem cell
• gene therapy
• gene addition
• gene editing
• value

Article highlights

• Gene therapy is an emerging area of science in which different approaches are taken to replace dysfunctional genes or add new ones. Gene therapies represent major advances in the treatment of genetic disorders, such as sickle cell disease (SCD), for which limited treatment options are available, as they hold curative promise; however, this is not without risk.

• SCD is rare genetic disorder caused by an inherited structural defect in the beta globin gene. It is a lifetime disorder characterized by painful vaso-occlusive crises, anemia, and increased risk of stroke and other significant comorbidities, leading to increased utilization of health care resources.

• Gene therapies are currently being studied for use in SCD. Both gene editing and gene addition are at early stages of development in clinical trials and may hold promise as cures and for additional life-long benefits such as increased quality of life and decreased disease burden.

• Current mainstay treatments for SCD are hydroxyurea and blood transfusions. Other available treatment options include crizanlizumab, voxelotor, L-glutamine, and hematopoietic stem cell transplantation. Use of these therapies is limited by various barriers such as poor acceptability, increased number of health care visits, and lack of matched donors.

• The one-time administration and expected upfront costs of gene therapy warrant accurate estimations of value including costs offset by lower lifetime health care resource use, improved productivity, and improved quality of life for patients and families.

• A major challenge to estimating the value of gene therapies for SCD is determining the impact on quantity and quality of life without available long-term efficacy and safety data. In addition, challenges exist in establishing a willingness-to-pay (WTP) threshold for rare diseases in various regions, including LMICs.

• Efforts to determine the value of these therapies and social influences affecting access to treatment are important to ensure adequate availability of and equitable access to these emerging therapies in regions most impacted by SCD.

Acknowledgments

The authors wish to acknowledge collaborators from the University of Washington and the Fred Hutchinson Cancer Research Center: Z. Baldwin, Z. Elsisi, K. Johnson, C. Henry, W. Wright. The authors also appreciate the valuable insights and suggestions provided by the members of the Clinical and Economic Analysis Initiative Expert Panel of the NHLBI Cure Sickle Cell Initiative.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer on this manuscript declares acting as an advisory board member for Octapharma, Dova, Principia and Shionogi, a consultant for Novartis, Shionogi, Dova, Principia, Argenx, Rigel and Bayer, and has received research funding from Sysmex, Novartis, Rigel, Principia, Argenx, Dova, Octapharma and AstraZeneca (sickle cell disease study). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was funded by the National Heart, Lung and Blood Institute, Cure Sickle Cell initiative (OTA Numbers: OT3HL152448, OT3HL151434)