Rare Daily Staff

The U.S. Food and Drug Administration Genentech approved Hemlibra to prevent or reduce the frequency of bleeding episodes in children and adults with hemophilia A who have developed inhibitors for factor VIII replacement therapies. 

Hemophilia A is an inherited disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60 percent of people living with a severe form of the disorder. People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding.

Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles. These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.

A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding. About one-third of people with severe hemophilia A can develop inhibitors to factor VIII replacement therapies, putting them at greater risk for life-threatening bleeds or repeated bleeds that can cause long-term joint damage. Most people with hemophilia A who develop inhibitors typically infuse special blood products known as bypassing agents that work around the inhibited factor to allow for clotting.

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. It is injected subcutaneously once weekly. In two of the largest pivotal clinical studies for people with hemophilia A with inhibitors, Hemlibra was shown to substantially reduce bleeds in adults and children.

“People with hemophilia A who develop inhibitors face significant challenges preventing bleeds and typically require infusions of medicine multiple times a week, which can be especially difficult for young children and their families,” said Guy Young, director of Hemostasis and Thrombosis Program, Children’s Hospital Los Angeles, and professor of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California. “This new medicine has been shown to reduce the frequency of bleeds compared to the currently available medicines and only needs to be injected once a week. This could make a meaningful difference for these children.”

In the first of two late-stage studies, people 12 years of age or older with hemophilia A with inhibitors who received Hemlibra prophylaxis had a statistically significant reduction in treated bleeds of 87 percent compared to those who received no prophylaxis. In a first-of-its-kind intra-patient analysis, Hemlibra prophylaxis resulted in a statistically significant reduction in treated bleeds of 79 percent compared to previous treatment with bypassing agent prophylaxis collected in a non-interventional study prior to enrollment.

Interim results from a second, pivotal late-stage study in children younger than 12 years of age with hemophilia A with inhibitors showed that 87 percent of children who received Hemlibra prophylaxis experienced zero treated bleeds. In an intra-patient analysis of 13 children who had participated in the NIS, Hemlibra prophylaxis resulted in a 99 percent reduction in treated bleeds compared to previous treatment with a bypassing agent either as prophylaxis or on-demand.

The most common adverse events occurring in 10 percent or more of people treated with Hemlibra in pooled studies were injection site reactions, headache and joint pain (arthralgia).

“Today’s approval of Hemlibra represents an important advancement for people with hemophilia A with inhibitors, who have struggled to manage their bleeding disorder and haven’t had a new medicine in nearly 20 years,” said Sandra Horning, chief medical officer and head of global product development for Genentech. “We believe Hemlibra will improve protection against bleeds and reduce the treatment administration burden for people with hemophilia A with inhibitors, and we are committed to helping them access this medicine.”

Hemlibra is expected to be available in the United States shortly. The FDA had granted Hemlibra Priority Review and Breakthrough Therapy designation in people 12 years of age or older with hemophilia A with inhibitors. Data from Genentech’s two late-stage studies are being reviewed under accelerated assessment by the European Medicines Agency and submissions to health authorities around the world are ongoing.

November 22, 2017

Photo: Sandra Horning, chief medical officer and head of global product development for Genentech

X