Juliana Biondo, MD: Current, Future Therapies for Hemophilia A

Juliana Biondo, MD

The introduction of Roctavian (valoctocogene roxaparvovec-rvox), an adeno-associated virus (AAV)-mediated gene therapy, has sparked excitement in the hemophilia A community. Though, its predictability and durability over time has not been fully observed. Current data for the therapy, which supported the US Food and Drug Administration (FDA) approval, is limited to a specific population of adults with hemophilia A who meet certain criteria.

Adult patients with severe hemophilia A may achieve a significant reduction in annualized bleed rate (ABR) and in clotting factor use with Roctavian if they have congenital factor VIII (FVIII) deficiency with FVIII activity < 1 IU/dL, and are without antibodies to AAV serotype 5 (AAV5) detected by an FDA-approved test.

However, the drug also demonstrated an association with liver abnormalities in these patients. Juliana Lagrasta Biondo, MD, executive director of Oncology/Hematology, Genentech, detailed an overview of current hemophilia A treatment options in a written interview. She emphasized the safety and efficacy of prophylactic therapy Hemlibra (emicizumab-kxwh), which was approved by the FDA after achieving significant control of bleeding episodes.

HCPLive: Hemlibra has been approved for more than 5 years and is currently the only preventative medicine available for individuals with hemophilia A, with or without FVIII inhibitors. Could you explain how Hemlibra works and its impact on patient outcomes?

Biondo: Hemlibra is a bispecific antibody, designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and help restore the blood clotting process for people with hemophilia A.

In pivotal trials, Hemlibra significantly reduced treated bleeds compared with no prophylaxis (HAVEN 1, HAVEN 2, HAVEN 3) and demonstrated clinically meaningful bleed control (HAVEN 4). Hemlibra has many important firsts, including being the first medicine to significantly reduce treated bleeds compared with:

• Prior FVIII prophylaxis in people with hemophilia A without FVIII inhibitors
• Prior bypassing agent (BPA) prophylaxis in people with FVIII inhibitors
• The first subcutaneous treatment for hemophilia A available with multiple dosing options.

Hemlibra provides steady plasma levels and clinical efficacy in terms of sustained bleed protection, which is independent of changes in FVIII activity levels, in individuals with hemophilia A with and without factor VIII inhibitors and across a range of severities.

In the US, Hemlibra is now the most prescribed prophylactic treatment for hemophilia A. Since its initial FDA approval, more than 20,000 people have received Hemlibra across the globe. The growing body of real-world experience is consistent with the clinical trial data.

Looking ahead, what are your expectations for the future of hemophilia A treatment? Do you anticipate any significant advancements or changes in the coming years?

We are continuing to evaluate Hemlibra in new areas of patient need and populations. While the treatment and management of severe hemophilia A are well-established, there is less information and treatment guidance on mild and moderate hemophilia A, which can lead to delayed or missed diagnosis of bleeding episodes and the consequences that come with it, impacting patients' lives.

The HAVEN 6 study aims to evaluate the safety and efficacy profile of Hemlibra in moderate and mild populations without FVIII inhibitors.

Guidelines recommend that preventative treatment for hemophilia A should be initiated at an early age. Interim data from the Phase III HAVEN 7 study demonstrated the efficacy and safety of Hemlibra prophylaxis in infants up to 12 months of age with severe hemophilia A without FVIII inhibitors.

These patients will be followed for seven years to evaluate the ongoing safety and efficacy of Hemlibra through these pivotal years of childhood development.

Additionally, Roche’s acquisition of Spark Therapeutics includes SPK-8011, a gene therapy in development for the treatment of hemophilia A. This complements our existing portfolio and expands our capabilities in hemophilia A, allowing us to continue to address the unmet needs of people living with this condition and potentially provide additional treatment approaches.

NXT007, developed by Chugai (part of the Roche Group), is a next-generation bispecific antibody that is also currently being investigated as a treatment for people living with hemophilia A.