Impact of Novel Therapies Around the World

Margareth C. Ozelo, M.D., Ph.D.
Hemocentro UNICAMP, University of Campinas
Campinas, São Paulo, Brazil

Impact of Novel Therapies Around the World



Currently, prophylaxis is recognized as the standard of care for hemophilia. It became a possibility after several improvements of the available products for hemophilia treatment, and it has significantly enhanced the quality of life of these patients. For many decades, hemophilia treatment was based on replacement therapy using either plasma-derived or recombinant clotting factor products. With the use of different technologies, it was possible to develop modified recombinant products, including extended half-life (EHL) clotting factor concentrates, which help decrease the burden of several product infusions. More recently, the development of non-replacement therapies led to a considerable achievement in the management of severe hemophilia patients. These strategies include agonists that mimic factor activity, such as emicizumab, or agents that rebalance hemostasis. The latter is represented by agents that reduce the effect of natural anticoagulants, such as anti-tissue factor pathway inhibitor, serpins anti-protein C, and fitusiran, which decreases antithrombin production. These agents are viable alternatives to both inhibitor and noninhibitor patients. On the other hand, gene therapy provides the chance to achieve a steady-state factor VIII or IX expression with a single infusion. Since patients may reach normal factor levels after infusion, this therapy can potentially "cure" hemophilia.

Although we now have a wide range of possibilities for hemophilia care, access to treatment is considerably unbalanced worldwide. To close this gap, the World Federation of Hemophilia (WFH) started an important initiative, the Humanitarian Aid Program, to provide access to treatment for emergencies, acute bleeds, and surgeries and to provide prophylaxis for young children in low- and middle-income countries. This program started in 1996, and since then, more than 20,000 patients from 109 countries received products to be treated through the WFH Humanitarian Aid Program. A significant improvement happened in 2015 when the pharmaceutical companies Sobi and Sanofi committed to donating 1 billion units of EHL products (including factor VIII and IX) over 10 years to the WFH Humanitarian Aid Program. As a result, since 2016, it was possible to include patients in low-dose prophylaxis protocol and perform surgeries, most of them using EHL products, increasing the access to novel therapies in resource-constrained settings. In 2019, Roche also joined the program and started to donate emicizumab, and up to June 2021, 633 patients from 46 countries are on prophylaxis with donated emicizumab.

Considering future therapies, the AAV-based gene therapy for hemophilia is now a reality, and phase 1/2 clinical trials showed an expressive reduction in bleeding and factor consumption among participants. Currently, the phase 3 gene therapy clinical trials for hemophilia A and B are including participants not only from Europe and North America but also from Brazil, South Africa, Turkey, Saudi Arabia, and other countries. This may help achieve the target number of patients faster despite the difficulties related to the AAV-seroprevalence. Also, this will help the establishment of the infrastructure and knowledge for future potential market sites. In the future, gene therapy can become an important strategy in resource-constrained settings for hemophilia.


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