Details

Autor(en) / Beteiligte

• Braun, Manuela
• Lange, Claudia
• Schatz, Philipp
• Long, Brian
• Stanta, Johannes
• Gorovits, Boris
• Tarcsa, Edit
• Jawa, Vibha
• Yang, Tong-Yuan
• Lembke, Wibke
• Miller, Nicole
• McBlane, Fraser
• Christodoulou, Louis
• Yuill, Daisy
• Milton, Mark

Titel

Preexisting antibody assays for gene therapy: Considerations on patient selection cutoffs and companion diagnostic requirements

Ist Teil von

• Molecular therapy. Methods & clinical development, 2024-03, Vol.32 (1), p.101217-101217, Article 101217

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for in vivo gene therapies. Anti-AAV antibodies (AAV Abs) can interact with the viral capsid component of an AAV-based gene therapy (GT). Therefore, patients with preexisting AAV Abs (seropositive patients) are often excluded from GT trials to prevent treatment of patients who are unlikely to benefit1 or may have a higher risk for adverse events outweighing treatment benefits. On the contrary, unnecessary exclusion of patients with high unmet medical need should be avoided. Instead, a risk-benefit assessment that weighs the potential risks due to seropositivity vs. severity of disease and available treatment options, should drive the decision if patient selection is required. Assays for patient selection must be validated according to their intended use following national regulations/standards for diagnostic assays in appropriate laboratories. In this review, we summarize the current process of patient selection, including assay cutoff criteria and related assay validation approaches. We further provide considerations on regulatory requirements for the development of in vitro diagnostic tests supporting market authorization of a corresponding GT. [Display omitted] Patients with preexisting antibodies to a gene therapy product are often excluded from treatment based on arbitrary cutoffs. Benefit-risk-based considerations and determination of clinically relevant cutoffs using a diagnostic assay, validated according to its intended use in adequate laboratories, could improve patient selection and their treatment.