Monitoring the Impact of Gene Therapy in Persons with Hemophilia
by Crystal Watson, President and CEO of ATHN

Gene therapy carries the potential for a functional cure of hemophilia. As we move towards the reality of commercial gene therapy treatments for people with hemophilia, it is incumbent upon the community to work together to monitor the impacts of this irreversible one-time therapy. There are many questions that need to be answered. What are the short and long-term safety profiles of these treatments? Why is clinical response, as measured by factor activity level, so variable? Why is durability of factor expression so variable? In order to address the gaps in current hemophilia gene therapy knowledge, data collection and surveillance must be a shared responsibility. Providers and persons with hemophilia receiving the treatment will need to work together to collect standardized data over a lifetime. Long-term data collection is essential in assisting regulators, manufacturers, clinicians, payers, and people with hemophilia and their families in monitoring the safety and effectiveness of these treatments.

Long-term collection of real-world safety and effectiveness data for people receiving hemophilia gene therapy should be considered standard of care. In the United States, this goal can best be supported by leveraging the established collaboration with ATHN and its Hemophilia Gene Therapy Outcomes Arm. The Hemophilia Gene Therapy Outcomes Arm is part ATHN Transcends Study which is rolling out across Hemophilia Treatment Centers (HTCs) in the United States. It is a pragmatic study designed to understand the outcomes of gene therapy with real-world practices across a wide range of products, including the safety of adeno-associated viral vector or lentiviral vector-mediated factor VIII and factor IX therapies when used for participants with hemophilia.

The Gene Therapy Outcomes Arm study aims to enroll all people with hemophilia A or B of any severity, with or without inhibitors, who have received or will receive a gene transfer product within 6 months. Data for the study is to be collected from participants at the time of enrollment and at the following timepoints relative to vector infusion: 3 months, 6 months, 1 year, 18 months, 2 years, and annually thereafter. Participants will be followed longitudinally for at least 15 years after vector infusion. Safety will be measured according to medical events established in the European Haemophilia Safety Surveillance System (EUHASS). In addition to the EUHASS defined events, the study will collect data for adverse events of special interest such as liver toxicity. ATHN will leverage its partner central laboratory organization, Versiti, Blood Center of Wisconsin, to perform factor and inhibitor assays and genetic testing for those who have not previously been tested as part of other projects.

The approach of a central study utilizing a central IRB and a central laboratory is designed to reduce the operational burden on HTCs. In the past it has been the common practice of each manufacturer to establish their own independent registries as products go to market. In our discussions with HTC partners, they have made it clear that this approach is no longer feasible as staffing levels are strained and institutions have implemented stricter controls on which studies can be opened due to the pandemic. In addition, this decentralized approach by manufacturers is unlikely to facilitate a global view of effectiveness.

As clearly articulated by the NHF Medical and Scientific Advisory Council, a global reach will be required to ensure a large enough participant pool to allow for robust evaluation and detection of low-incident safety events. To this end, ATHN has partnered with the international World Federation of Hemophilia Gene Therapy Registry (WFHGTR) to harmonize data collection between the Hemophilia Gene Therapy Outcomes Arm and the WFHGTR to support this global effort. ATHN will serve as the sole source of data from the United States to the WFHGTR. This will help minimize the data collection burden on HTC staff and facilitate the contribution of data from persons with hemophilia to this important global effort. ATHN looks forward to supporting our blood disorder partners as the reality of having commercial gene therapy products has finally arrived at our doorsteps. Stay tuned for more information as the Gene Therapy Outcomes Arm study gets ramped up at treatment centers. We will be sure to share the relevant data and the findings with the community.

Please contact support@athn.org for more information.