| Considering gene therapy in the context of new options for management of hemophilia Ben Samelson-Jones. |
Abstract
Considering gene therapy in the context of new options for management of hemophilia
B.J. Samelson-Jones
The Children’s Hospital of Philadelphia, Division of Hematology, Perelman Center for Cellular and Molecular Therapeutics, Philadelphia, PA
University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA
The goal of hemophilia treatments is to normalize hemostasis and optimize health and well-being. The aspirational promise of gene therapy is to provide safe, durable factor expression at a level sufficient to prevent bleeding in all recipients. Adeno associated viral (AAV) vectors for both hemophilia A and hemophilia B have recently received regulatory approval. There are also several additional AAV products for hemophilia A and B in the late-stage clinical development as well as alternative gene therapy approaches that have recently entered clinical trials. Current gene therapy products are, to different extents, partially redeeming the promise of gene therapy with notable differences between hemophilia A and hemophilia B drugs. All current gene therapy drugs for hemophilia have limitations and additional improvements will be necessary for hemophilia gene therapy to wholly deliver on its promise.
In parallel to the exciting developments of gene therapies, other novel technologies for promoting hemostasis have also been translated into new treatments for hemophilia, including extended half-life factor products and non-factor therapies (NFTs). Thus, people with hemophilia (PwH) and their medical teams are confronted with an array of therapeutic options. This range of treatment choices allows PwH to prioritize and balance aspects of the drugs most important to them, such as hemostatic efficacy, safety considerations, and convenience of administration. Other considerations might include the robustness of the available clinical data as well as degrees of comfort with uncertainty.
However, the considerations around gene therapy are unique. As current AAV approaches only allow a single vector administration for the foreseeable future, the risks and benefits of current AAV drugs need to be weighed, not only against existing alternative treatments, but also against forthcoming AAV drugs. The nuances of AAV gene therapy clinical trial data need to be fully appreciated, including differences in observed and theoretical safety profiles, limitations of outcome data, and factor assay discrepancies. The long-term safety and efficacy of AAV gene therapy can also only currently be hypothesized about. PwH and their medical teams must balance a number of considerations when deciding about gene therapy in the context of current extended-half-life factors and NFTs.
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