Transplantation of gene-modified haematopoietic stem cells: Application and clinical considerations

Alessandrini, Marco; Krause, Karl-Heinz; Speck, Roberto F.; Pepper, Michael Sean

doi:10.7196/samj.2019.v109i8b.013910

Cited by 4 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An RCT may also be inappropriate for ATMPs, which often are administered at one point in time but may have very late effects. Recent regulatory marketing authorisations of some ‘single-treatment cures’ for life-threatening and previously incurable diseases suggest that with these new treatment modalities a new era of modern medicine has been entered [ 9 , 44 , 45 ]. Development of techniques involving ex vivo gene modification of haematopoietic stem cells (HSC) for autologous transplantation have led to the development and approval in Europe of Strimvelis ® (autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene) for a rare primary immune deficiency and Zynteglo ® (betibeglogene autotemcel) for beta-thalassaemia.…”

Section: New Treatment Modalitiesmentioning

confidence: 99%

“…The prominent place of the RCT in the evidence generation ‘toolbox’ is also being challenged by innovations in at least two areas [ 3 ]. First, the RCT may be unsuitable for evaluating new treatment modalities such as precision medicine or gene and cell therapies, the latter often referred to as Advanced Therapeutic Medicinal Products (ATMPs) [ 9 – 13 ]. Second, alternative approaches to evidence generation represent another area where innovation may have implications for the relevance of the RCT [ 14 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Randomised Controlled Trial at the Intersection of Research Ethics and Innovation

Callréus¹

2022

Pharm Med

View full text Add to dashboard Cite

The randomised controlled trial (RCT) has been considered for a long time as the gold standard for evidence generation to support regulatory decision making for medicines. The randomisation procedure involves an ethical dilemma since it means leaving the treatment choice to chance. Although currently contested, the ethical justification for the RCT that has gained widespread acceptance is the notion of ‘clinical equipoise’. This state exists when “there is no consensus within the expert clinical community about the comparative merits of the alternatives to be tested”; it is argued that this confers the ethical grounds for the conduct of an RCT. The prominent position of the RCT is being challenged by new therapeutic modalities for which this study design may be unsuitable. Moreover, alternative approaches to evidence generation represent another area where innovation may have implications for the relevance of the RCT. Against the backdrop of the debate around the equipoise principle and some recent therapeutic and data analytical innovations, the aim of this article is to explore the current standing of the RCT from a regulatory perspective.

show abstract

Section: New Treatment Modalitiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Randomised Controlled Trial at the Intersection of Research Ethics and Innovation

Callréus¹

2022

Pharm Med

View full text Add to dashboard Cite

show abstract

“…This variability in cell source, when coupled with complex expansion protocols and long lead times, typically results in high manufacturing costs and reimbursement challenges. However, despite these challenges, autologous therapies offer the considerable advantage of avoiding immune responses, enhancing efficacy owing to long-term engraftment times and holding the potential for re-administration 239 . It should be noted that autologous therapies may still pose the risk of immune response via transgenes that encode antigens that are xenogeneic or congenitally absent.…”

Section: Introductionmentioning

confidence: 99%

Engineering the next generation of cell-based therapeutics

Bashor

Hilton

Bandukwala

et al. 2022

Nat Rev Drug Discov

170

View full text Add to dashboard Cite

Cell-based therapeutics are an emerging modality with the potential to treat many currently intractable diseases through uniquely powerful modes of action. Despite notable recent clinical and commercial successes, cell-based therapies continue to face numerous challenges that limit their widespread translation and commercialization, including identification of the appropriate cell source, generation of a sufficiently viable, potent and safe product that meets patient- and disease-specific needs, and the development of scalable manufacturing processes. These hurdles are being addressed through the use of cutting-edge basic research driven by next-generation engineering approaches, including genome and epigenome editing, synthetic biology and the use of biomaterials.

show abstract

“…Большой проблемой является и невозможность стандартизации как производства, так и конечного продукта в большинстве случаев (особенно для аутологичных препаратов, когда характеристики и объем конечного продукта могут значительно варьировать) [1]. Кроме того, не всегда требования нормативных документов по объему, дизайну и продолжительности исследований могут быть выполнены разработчиками; особенно это касается препаратов для лечения генетических заболеваний [2,3]. Поэтому разработка, производство, проведение доклинических (ДКИ) и клинических исследований (КИ) препаратов на основе клеток и тканей человека представляют собой процесс значительно более сложный, трудоемкий, долгосрочный и дорогостоящий по сравнению с традиционными лекарственными препаратами (ЛП), а рассмотрение регуляторными органами результатов разработки с целью вывода на рынок таких препаратов всегда основано на персонализированном подходе [4][5][6][7].…”

unclassified

World practice of providing scientific advice on the development and authorisation of innovative medicines

Мельникова¹,

Меркулова²,

Меркулов

2021

Biological Products. Prevention, Diagnosis, Treatment

View full text Add to dashboard Cite

Current challenges to healthcare, i.e. the emergence of new diseases, lack of therapies for known diseases and life-threatening conditions, identification of patients who do not respond to standard treatment, on the one hand, and the evolution of scientific understanding of disease processes, medicines, therapies, causes of treatment failures, and implementation in clinical practice of innovations related to molecular biology and genetic engineering, on the other hand, create conditions and opportunities for the development of innovative medicinal products. A relatively new class of medicines is based on human cells and tissues (the term used in Russian legislation is biomedical cell products, BCP). However, the inability to accurately predict the efficacy and financial rewards of such medicines for pharmaceutical companies, as well as significant labour and financial costs associated with their development and clinical use, hinder their entry into the market. The aim of the study was to analyse the foreign regulatory setting for the development and launch of human cell- and tissue-based products, as well as approaches of foreign regulatory authorities to scientific advice, which can be drawn upon by the Russian expert authority when providing advice to BCP developers. The paper summarises the results of analysis of regulations establishing the procedure for providing scientific advice by EU, USA, and Russian regulatory authorities, and analyses the advice provided for the human cell- and tissue-based products which are now authorised in the EU and USA. The analysis of advice provided by foreign regulatory authorities shows that the largest number of consultations were given for medicinal products based on genetically modified cells for the treatment of cancer and genetic diseases. The questions were mainly related to the contents of specifications for finished pharmaceutical products, safety evaluation, curtailing of preclinical studies due to the lack of relevant animal/disease models, the number of subjects and efficacy endpoints in clinical studies, assessment of the appearance of replication-competent retroviruses.

show abstract

Transplantation of gene-modified haematopoietic stem cells: Application and clinical considerations

Cited by 4 publications

References 26 publications

The Randomised Controlled Trial at the Intersection of Research Ethics and Innovation

The Randomised Controlled Trial at the Intersection of Research Ethics and Innovation

Engineering the next generation of cell-based therapeutics

World practice of providing scientific advice on the development and authorisation of innovative medicines

Contact Info

Product

Resources

About