Towards a global multidisciplinary consensus framework on haemophilia gene therapy: Report of the 2nd World Federation of Haemophilia Gene Therapy Round Table

Abstract

Introduction:With approval of gene therapy for haemophilia likely in the near future, policy frameworks are needed to guide the path forward for this disruptive and novel therapeutic advance. Aim:The WFH has initiated a series of multi-stakeholder Gene Therapy Round Tables (GTRT) to better understand where guidance is needed and develop initial consensus statements to inform policy. Methods:The first day of the 2nd GTRT was devoted to didactic presentations on models of access to gene therapy, payment and health technology assessment considerations, regulatory issues and the generation of evidence on safety and durable efficacy of gene therapy products. On the second day, participants were tasked with developing and voting on consensus statements that reflected the information presented and multistakeholder views expressed during discussions in the 1st and 2nd WFH GTRTs. The statements covered global access to gene therapy for all people with haemophilia (PWH), collection of long-term safety and efficacy data, ensuring gene therapy is available for all subgroups of PWH including those who have been largely excluded from clinical trials and characterizing acceptable and ideal factor expression levels for gene therapy products. Results:The first 3 statements achieved consensus (at least 80% agreement) by this group of experts. The statement on identifying an ideal and an acceptable factor level expression elicited a lively discussion but failed to achieve consensus by this group.Conclusions: This issue of ideal and acceptable factor level expression and other unresolved issues will be brought to the 3rd WFH GTRT in 2020. K E Y W O R D Schallenges, consensus, gene therapy, global, haemophilia, round table 444 | PIERCE Et al.

The German Hemophilia Registry: Growing with Its Tasks

“…Investigational medicinal products include Valoctocogene Roxaparvovec (previously BMN 270) [46][47][48] and PF-07055480 [49] for treatment of HA and Fidanacogene Elaparvovec (previously PF-06838435) [50], FLT180a [51], and AMT-061 [52] for treatment of HB. As the WFH Gene Therapy Round Table suggests recording gene therapy for hemophilia in central or national registries [53,54], considering upcoming gene therapies in the redesign of the dhr seemed prudent. To harmonize clinical trials on hemophilia gene therapy in the jurisdiction of the United States, the Food and Drug Administration (FDA) issued the Guidance "Human Gene Therapy for Hemophilia" [20], which has influenced the design of many clinical trials since the publication of its first draft in 2018.…”

Gene Therapy in Hemophilia: Recent Advances

“…Another important aspect will be reaching a consensus on the use of a multidisciplinary approach to the application of the new gene therapy protocols in hemophilia [ 46 ]. Treatment of hemophilia has always been multidisciplinary, with the patient at the center and practitioners from different departments of the hospital working as a team to ensure the delivery of an optimal standard of care [ 47 ].…”

Reimbursing the value of gene therapy care in an era of uncertainty

“…In lower bands, PWH with lower levels of factor may still not need prophylactic treatment, although it may be argued that sub‐clinical bleeding may still occur 31 . The details in examples such as this could be agreed to by a Delphi‐like process to achieve expert consensus until population data are available 32 . It will be important to consider that the two major assays, the one‐stage and chromogenic are discrepant by 60% for both Factor VIII and the Padua variant of Factor IX, a significant difference for purposes of discriminating between circulating factor level categories (Table 3).…”