Steven Pipe, MD, of the University of Michigan, discusses the results of HAVEN 7, a Phase 3 trial testing the efficacy and safety of emicizumab to prevent bleeding episodes in patients under 12 months of age with hemophilia A.
Hemophilia A is a hereditary hemorrhagic disorder resulting from a congenital scarcity of factor VIII. This type of hemophilia manifests as protracted and excessive bleeding either spontaneously or secondary to trauma. The main manifestations of hemophilic bleeding are bleeding into joints or serious internal bleeding, including intracranial hemorrhage.
Factor concentrate replacement has traditionally been used in the prophylactic treatment of hemophilia A. However, the intravenous administration of these factor concentrates can be a challenge. Prophylaxis is also hard to start at early ages, usually having to wait until patients are between about 9-15 months of age. This has left a significant treatment gap where physicians can only treat infants reactively in the case of bleeding events. Emicizumab is a bispecific antibody that targets factors IXa and X, resulting in activation of factor X and mimicking the actions of factor VIII. It also can be administered subcutaneously.
HAVEN 7 Study
The study enrolled 55 infants under 12 months, with a majority being previously untreated patients. Emicizumab was administered with a loading dose followed by a once-weekly maintenance dose. Plasma levels of the bispecific antibody were found to be therapeutic even in the youngest infants.
The effectiveness of emicizumab was evaluated based on bleeding events. The annualized bleeding rate was impressively low following treatment. More than half of the infants had zero treated bleeds throughout the one-year follow-up. Patients also demonstrated excellent plasma levels. After the loading dose, plasma levels went up to about 62 ug/mL.
As noted by Dr. Pipe, safety concerns were addressed, with no intracranial hemorrhage reported. Adverse events were generally low grade, with transient injection site reactions being the most common. Importantly, no participants tested positive for anti-drug antibodies against emicizumab, and the rate of factor VIII inhibitors was relatively low.
Future plans involve a seven-year follow-up to assess the long-term impact on inhibitor rates, joint health, and the overall natural history of initiating prophylaxis early in life.
For more information on hemophilia A and other rare hematological disorders, visit https://checkrare.com/diseases/hematologic-disorders/