The World Federation of Hemophilia Gene Therapy Registry

Introduction

Gene therapy for hemophilia is an evolving therapeutic modality, with many challenges and unresolved questions that will not be fully answered at the completion of current ongoing clinical trial programs. With regulatory approval of the first gene therapy product(s) expected in 2020-21 in the US and Europe, there is an urgent need for a single global hemophilia gene therapy registry, to collect long-term data on safety, and variability and durability of efficacy. The World Federation of Hemophilia (WFH), in collaboration with the International Society of Thrombosis and Hemostasis (ISTH), the European Association for Haemophilia and Allied Disorders (EAHAD), the European Haemophilia Consortium (EHC), the US National Hemophilia Foundation (NHF), the American Thrombosis and Hemostasis Network (ATHN), industry gene therapy development partners and regulatory liaisons, have developed the Gene Therapy Registry (GTR), designed to collect long-term data on all people with hemophilia (PWH) who receive gene therapy.

Objectives

The primary objective of the WFH GTR is to record the long-term safety of gene therapies in patients with hemophilia. The secondary objectives of the WFH GTR are to determine the long-term efficacy and the durability, assessed by changes in bleeding rate and plasma factor VIII or IX activity level post-gene therapy infusion. Additionally, changes in quality of life, assessed by the EQ-5D-5L and burden of disease, assessed by the Patient Reported Outcomes, Burdens, and Experiences (PROBE) scale, will be assessed post-gene therapy infusion.

Methods

The WFH GTR is a prospective, observational, and longitudinal registry developed under the guidance of a multi-stakeholder GTR Steering Committee (GTR SC), composed of health care professionals, patient advocates, industry representatives, and regulatory agency liaisons.

All PWH who receive gene therapy, by clinical trial participation or commercially post-approval, will be invited to enroll in the registry through their hemophilia treatment centers (HTCs). Patients who receive gene therapy via a clinical trial, will be enrolled in the registry following the closure of their trials. The registry aims to enroll 100% of PWH globally who receive gene therapy.

Through an iterative process, and following guidance of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), the WFH GTR SC has developed a core set of data to be collected on all patients with hemophilia, who receive gene therapy.

Collection of data will be requested quarterly during the first year post-gene therapy infusion and annually thereafter, over the patient’s lifetime. Outreach to HTCs began in August 2020 with initiation visits beginning in October 2020. The registry will go live in January 2021.

Results

The core data set includes demographic information, vector infusion details, safety, efficacy, quality of life and burden of disease (see table 1).

Conclusions

There are many unknowns on the long-term safety and efficacy of gene therapy for hemophilia. It is incumbent on the bleeding disorders community to ensure all patients are followed in one registry over their lives. This ensures rare adverse events, in a small patient population, over a large geographical area, will be detected.