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Advisor(s)
Abstract(s)
Introduction: Sickle cell disease (SCD) is an inherited disorder characterized by polymerization of deoxygenated hemoglobin and microvascular obstruction. Generalized, it affects millions of people over 85% from low-and-middle-income countries. The cardinal feature is generalized pain referred to as vaso-occlusive crises (VOC), multi-organ damage, and premature death.). SCD is the most prevalent inherited reduced life-threatening disorder in the world and over 85% of the world's 400,000 annual births occur in low-and-middle-income countries. In the UK with about 250 annual births (1:200 live births, and over 14,00 living with the disorder. For decades span. Since 1998 Hydroxyurea remained the only disease-modifying therapy until the FDA approved L-glutamine (2017), Crizanlizumab and Voxelotor (2019), and gene therapies (Exa-cel and Lovo-cel, 2023). Areas covered: A literature review, we discuss established and new treatments. We provide an in-depth review of key clinical trials from 2013-2023. However, for pragmatic purposes we have approached this review in line with the different mechanisms of action, considering the possible options for the search performed in Pubmed Central using the search terms [sickle cell disease] or [sickle cell anemia] and the known treatments, i.e. Hydroxycarbamide/Hydroxyurea, L-Glutamine, Voxelotor, Crizanlizumab, Mitapivat, Etopivat, gene therapy, hematopoietic stem cell transplantation, and combination therapy. Clinical trials performed in the last 10 years (November 2013 - November 2023) were selected. Expert opinion: In our opinion section, we recommend the consideration of combination therapies for specific complications such as VOCs, pain, and renal impairment as well as personalized medicine based on disease phenotype and patient patience characteristics. Following the wake of the recent approval of gene therapy for SCD, the more curative option is now a reality, the challenge is addressing how to address issues such as access, affordability, and shared decision-making with families.
Description
S Lugthart received funding to attend international conferences; Pfizer (2023), Vertex (2023), GBT (2022), and Novartis (2021). Consultancy work: Sanius Health, UK (2023). 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.
Keywords
Sickle cell disease Combination therapy Crizanlizumab Etavopivat Gene therapy Haematopoietic stem cell transplantation Hydroxyurea L-Glutamine Mitapivat Vaso-occlusive crises Voxelotor Anemia Fetal hemoglobin
Citation
Lugthart S, Ginete C, Kuona P, Brito M, Inusa BP. An update review of new therapies in sickle cell disease: the prospects for drug combinations. Expert Opin Pharmacother. 2024;25(2):157-70.
Publisher
Taylor & Francis