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Review
. 2024 Jun 22;32(3):101287.
doi: 10.1016/j.omtm.2024.101287. eCollection 2024 Sep 12.

Consensus-driven target product profiles for curative sickle cell disease gene therapies

Daima Bukini  1 , Julie Makani  1   2   3 , Joseph McCune  4 , Dennis Lee  4 , Cathy Bansbach  5 , Serena De Vita  6 , Dominic Kemps  7 , Elianna Amin  8 , Jonathan Spector  9 , John Tisdale  10
Affiliations
Review

Consensus-driven target product profiles for curative sickle cell disease gene therapies

Daima Bukini et al. Mol Ther Methods Clin Dev. .

Abstract

Therapeutic innovation to address sickle cell disease (SCD) is at a historical apex, characterized by a drug discovery, development, and commercialization landscape that includes potentially curative gene therapies. Given the wide geographic distribution of SCD, with a major presence in Africa, it is imperative that new medicines are designed to meet the specific needs of persons with SCD everywhere. Target product profiles (TPPs) detail the desired attributes of new medicines and serve as a guide for drug developers. To support research efforts for curative treatments for SCD, we mobilized a large multi-disciplinary expert group to generate consensus-driven TPPs for ex vivo and in vivo SCD gene therapies, utilizing a modified Delphi methodology supplemented with virtual workshops. The main findings are TPPs that describe 20 minimal and optimal criteria for novel gene therapy products in categories of scope (3 criteria), performance/safety (11 criteria), manufacturing (4 criteria), and administration (2 criteria). TPPs for ex vivo and in vivo products differed in some performance/safety criteria and all criteria pertaining to manufacturing and administration. These outputs will ideally support development of durable treatments that are safe, efficacious, and practical for persons with SCD in global settings.

Keywords: Africa; drug discovery; gene therapy; sickle cell disease; target product profile.

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Conflict of interest statement

S.D.V., E.A., and J.S. are employees of Novartis Biomedical Research.

Figures

None
Graphical abstract
Figure 1
Figure 1
Estimates of the global distribution of sickle cell disease in regions where it is highly prevalent
Figure 2
Figure 2
Methodology to generate target product profiles for gene therapy for sickle cell disease by multi-stakeholder consensus
See this image and copyright information in PMC

References

    1. GBD 2021 Sickle Cell Disease Collaborators Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000 – 2021: a systematic analysis from the Global Burden of Disease Study. Lancet Haematol. 2023;10:e585–e599. - PMC - PubMed
    1. Tshilolo L., Tomlinson G., Williams T.N., Santos B., Olupot-Olupot P., Lane A., Aygun B., Stuber S.E., Latham T.S., McGann P.T., et al. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N. Engl. J. Med. 2019;380:121–131. - PMC - PubMed
    1. sickle cell disease Commissioners Electronic address davidrees@kclacuk The Lancet Haematology Commission on sickle cell disease: key recommendations. Lancet Haematol. 2023;10:e564–e567. - PubMed
    1. U.S. Food & Drug Administration Approved cellular and gene therapy products. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-produ...
    1. European Medicines Agency Approved Advanced Therapy Medicinal Products (ATMPs) https://www.ema.europa.eu/en/documents/report/cat-quarterly-highlights-a...

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