Clinical Development of Gene Therapy Needs a Tailored Approach: A Regulatory Perspective from the European Union

Narayanan, Gopalan; Cossu, Giulio; Galli, Maria Cristina; Flory, Egbert; Ovelgönne, Hans; Salmikangas, Paula; Schneider, Christian K.; Trouvin, Jean‐Hugues

doi:10.1089/humc.2013.230

Cited by 14 publications

(16 citation statements)

References 6 publications

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“…In parallel, the regulatory framework is evolving with the progress of technology and the increasing experience being gathered from human trials. The Food and Drug Administration (FDA) and the EMA have published recommendations for gene therapy products (Narayanan et al 2014). The need for shorter and less expensive paths to clinical trials and conditional approval relying more on human data for safety and efficacy has now been recognised, as exemplified by the FDA's Breakthrough Therapies programme and the EMA's Adaptive Pathways and Priority Medicines (PRIME) schemes which were launched in 2012, 2014 and 2016, respectively (Mullard 2016).…”

Section: Gene Therapy Requires An Innovative Economic Model For Succementioning

confidence: 99%

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Baruteau

Waddington

Alexander

et al. 2017

J of Inher Metab Disea

104

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Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics.

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Section: Gene Therapy Requires An Innovative Economic Model For Succementioning

confidence: 99%

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Baruteau

Waddington

Alexander

et al. 2017

J of Inher Metab Disea

104

View full text Add to dashboard Cite

show abstract

“…Opponents of more explicit guidance on preclinical design standards in TAGs might argue that the determination of the sufficient set of preclinical efficacy studies to inform phase I/II trials is too case specific. Vestergaard et al claim that for innovative medicines with high complexity, classical regulatory approaches based on guidelines are too inflexible and thus insufficient (Vestergaard et al, 2013;Narayanan et al, 2014). Instead, they argue that regulators should establish preclinical study recommendations on a case-by-case approach.…”

Section: Discussionmentioning

confidence: 99%

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross‐sectional study

Langhof

Chin

Wieschowski

et al. 2018

British J Pharmacology

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“…Three genome editing tools are mostly used now: ZFN and TALEN systems which are at a more advanced stage, and CRISPR/Cas9 being in very early clinical development, thus providing us an opportunity to proceed with their further development and regulatory discussions [14,16].…”

Section: Genome Editing: Variety Of Tools and Productsmentioning

confidence: 99%

“…In this article, we will focus primarily on current regulatory practice supporting development of the first clinically oriented products for treatment of disease, such as HIV, Hepatitis B and cancer. Moreover, regulations and guidance are still developing especially, in Russia and will require a permanent dialogue between regulatory agencies and scientists [14].…”

Section: Introductionmentioning

confidence: 99%

Genome editing: development and regulatory challenges

Samsonov¹

2017

CTT

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Genome editing tools can be mostly used to introduce, remove, or substitute one or more specific nucleotides at a specific site in an organism's genome, and is achieved with the use of protein-nucleotide complexes. Several classes of these complexes exist, Zinc Finger Nuclease (ZFN), transcription activator-like effector nuclease (TALEN and the most recent discovery-Clustered regularly interspaced short palindromic repeats /CRISPR associated protein 9 (CRISPR/Cas9). The technology belongs to a growing list of personalized therapies and requires special attention to perform development, standardization of manufacturing for every patient, robust preclinical and clinical program addressing key challenges of the new technology, e.g. "off-target" effects. The ethical aspects of these tools are also quite critical.

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Clinical Development of Gene Therapy Needs a Tailored Approach: A Regulatory Perspective from the European Union

Cited by 14 publications

References 6 publications

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Preclinical efficacy in therapeutic area guidelines from the U.S. Food and Drug Administration and the European Medicines Agency: a cross‐sectional study

Genome editing: development and regulatory challenges

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