Bleeding Events and Safety Outcomes in Patients with Hemophilia A Inhibitors

Andrew Black

We spoke with Dr. Gallia Levy, Associate Group Medical Director, at Genentech about data presented at the 58th American Society of Hematology (ASH) annual meeting in San Diego, CA on bleeding events and safety of patients with hemophilia a inhibitors. 

 Can you describe the current management of hemophilia A and the concern for antibody development?

People with hemophilia A, a rare genetic bleeding disorder, do not have or make enough of an essential blood clotting protein called factor VIII. Depending on the severity of the disorder, they can be susceptible to severe, uncontrolled bleeding, especially into the joints.
Standard treatment for hemophilia A usually involves intravenous infusions of replacement factor VIII. However, approximately one in four people develop antibodies, or inhibitors, which can bind to and prevent these replacement factors from working. This is a major challenge and makes it difficult, if not impossible, to control bleeding with replacement factor VIII therapy.
Therapies for people with inhibitors are currently limited to bypassing agents, which require treatment up to every other day to prevent bleeds because of their shorter half-lives (the time the medicine stays in the body), and there remains a need for more effective options. Data from our non-interventional study (NIS), for example, showed people treated prophylactically with bypassing agents still had a high number of bleeds per year.

Why is a real world assessment of hemophilia patients with antibodies needed?

The advantage of this type of study is that data are self-reported by the participants in near real-time, allowing for the collection of accurate and complete information. The NIS currently represents the largest cohort of people with hemophilia A with inhibitors in a clinical trial of this type, and the data generated will inform ongoing research and treatment.
The study is also helping to inform the Phase III clinical development program for our investigational medicine, emicizumab, enabling comparisons of the same individuals before and after treatment with emicizumab. This is the first report of prospective real-world data being collected for use as a valid historical control for a pivotal study in hemophilia A.

Can you describe the methods and results of the study presented at ASH?

At ASH, we reported initial results from the first NIS cohort, which enrolled people 12 years of age or older with inhibitors against factor VIII being treated with current standard of care therapy (episodic or prophylactic bypassing agents) according to routine clinical practice. At the time of data cut-off, 103 individuals were enrolled (75 receiving episodic treatment and 28 receiving prophylaxis).
Participants carried a handheld device to record their bleeding events and hemophilia medication use in near real-time, with adverse events tracked during clinic visits. The results showed that in the prophylaxis arm, the median annualized bleeding rate (ABR) was high, suggesting the regimens used did not provide sufficient prevention or control of bleeding episodes, or that there was a lack of adherence. Additionally, a substantial proportion of bleeding events were not treated in either arm (47.2% in prophylactic and 35.5% in episodic), which could also be related to challenges with adherence or access, or to treatment burden.
These findings shed light on the unmet needs for people with hemophilia A and inhibitors and the potential challenges they face with current treatment options. Additionally, for the 64 participants in the NIS who had proceeded to enroll into the emicizumab Phase III study in people 12 years of age or older with hemophilia A and inhibitors, these results will set the benchmark for comparisons before and after their treatment with emicizumab in a way that has never been done before in a pivotal trial. Top-line results from this pivotal study are expected at the end of this year.


 Mahlangu J, Oldenburg J, Callaghan MU, et al. Bleeding Events and Safety Outcomes in Patients with Hemophilia a with Inhibitors: A Prospective, Multicenter, Non-Interventional Study. Presented at the 58th ASH Meeting San Diego, CA; December 3-6, 2016.  Abstract 3800. 
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