One year practical experience in factor VIII gene therapy

Introduction: We report on a 40 year old patient who received treatment with valoctocogene roxaparvovec. Factor VIII levels as well as thrombin generation was used to monitor the progress in therapy for 12 months.

Method: The patient with severe hemophilia A (deletion in exon 14) regularly visiting the hemophilia center in Magdeburg. The patient showed keen interest in gene therapy and passed through all preparatory procedures and tests (e.g. liver health, anti-AAV5 antibodies, immune status). Within the hub-spoke-model the patient received the gene therapy in the Vivantes-Klinikum in Berlin in late August 2023. The patient was treated with lonoctocog alfa for the following two weeks. Within another three weeks the dose was tapered. The patient received prednisolon for 6 weeks following an increase of transaminases. Blood was drawn from the patient by an external healthcare team weekly for the first 6 months and biweekly since. Serum was drawn for the determination of transaminases and creatine kinase. Citrate anticoagulated samples were centrifuged and frozen in dry ice immediatly after. Factor VIII was assessed using an one-stage assay (Actin FS) and a two-stage assay (Berichrom FVIII) on an Atellica COAG360 analyzer (all Siemens Healthineers). Thrombin generation was determined using the Bleedscreen assay on the Genesia platform (all Stago).

Results: After an initial delay, factor VIII levels rose to levels of 20% factor VIII in the one-stage assay and 15% in the two-stage assay. The factor of 1.3 between both assays has been consistent of the entire course of time. Thrombin generation increased parallel to the factor VIII levels. Over the first year of monitoring, there have been occasional slight oscillations in factor VIII levels. Also, the factor VIII levels were somewhat higher if blood was drawn during visits in the hemophila center.

Conclusion: The patient expressed complete satisfaction with the gene therapy, works regularly and enjoys daily physical activity. The cooperation between patient, hemophilia center, external healthcare team and within the hub-spoke-model has been and is exemplary.

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Artikel online veröffentlicht:
13. Februar 2025