Patient selection for hemophilia gene therapy: Real-life data from a single center

Background: While the number of individuals with hemophilia who are expected to be or have already been included in gene therapy trials has been regularly reported, the number of unscreened or excluded individuals, in addition to the reasons for exclusion, is mostly not reported.

Methods: We conducted an eligibility assessment of all people with severe hemophilia for gene therapy trials in one large Belgian hemophilia treatment center based on patient selection criteria of gene therapy trials and patients' profiling.

Results: Among 87 adult patients with severe hemophilia A and B, 11 aged ≥65 years and two women were excluded from analysis. Six patients were excluded because of inhibitor development. One patient exhibited active hepatitis C infection, one had insufficient exposure to factor VIII, and five had uncontrolled comorbidities, while two were enrolled in other trials and two abused alcohol. Overall, 43 patients were not screened owing to psychosocial factors. Among 14 patients accepting gene therapy, six had adeno-associated virus type 5 neutralizing antibodies and one had liver fibrosis. The number of patients who would accept gene therapy in the absence of strict clinical trial requirements was estimated at 36 (41.4%), irrespective of any exclusion criteria.

Conclusion: The majority of individuals with severe hemophilia could not be enrolled in gene therapy trials, almost half of them because of partly modifiable psychosocial reasons (49.4%). The proportion of candidates should substantially increase in the future, as eligibility criteria are likely to change and as more data on long-term efficacy and safety of gene therapy will become available.