Eligibility Criteria for Gene Therapy in Haemophilia
Gene therapy eligibility for haemophilia A and B includes similar criteria: appropriate age, severe disease, adequate liver health, and absence of pre-existing anti-AAV antibodies. 1
Core Eligibility Requirements
The key eligibility criteria for gene therapy candidates include:
Age requirements: Patients must meet minimum age thresholds established in clinical trials, though specific age cutoffs vary by study protocol 1
Disease severity: Severe haemophilia (factor levels <1 IU/dL) is the primary target population for gene therapy 1
Liver health: Adequate hepatic function is essential since AAV vectors transduce hepatocytes to produce clotting factors 1
Anti-AAV antibody status: The presence of pre-existing anti-AAV antibodies poses a significant limitation for gene therapy eligibility, as widespread exposure to naturally occurring AAV in the population creates immunity that can prevent successful transduction 1
Critical Exclusion Considerations
Several factors may disqualify patients from gene therapy:
Pre-existing liver disease: Since gene therapy targets hepatocytes and the most frequent adverse effect is elevated alanine aminotransferase levels (occurring in most haemophilia A participants and some haemophilia B participants), baseline liver dysfunction is problematic 1
Positive anti-AAV serology: This represents one of the most significant barriers to eligibility, as pre-existing antibodies can neutralize the vector before successful gene transfer 1
Important Clinical Caveats
Patients must understand that gene therapy requires strict laboratory monitoring, particularly in the first weeks and months after treatment, with prompt corticosteroid administration if transaminitis develops to preserve transgene expression. 1
The risk of AAV genome integration (approximately 0.01% of administered AAV) necessitates long-term monitoring for malignancy, though no causal relationship has been established with the 4 reported malignancies in clinical trials to date 1
Gene therapy may exhibit time-limited efficacy, particularly for haemophilia A, requiring ongoing assessment of factor levels and bleeding phenotype 1
Patients transitioning from severe to mild phenotype post-gene therapy may retain legacy joint damage and altered bleed risk from their years with severe disease, requiring different clinical management than typical mild haemophilia patients 2