Encouraging Results From a New Drug to Treat Hemophilia A

Horizons in Hemophilia, November 2015

Jeff Cornett RN MSN, Vice President of Research & Public Policy

Hemophilia A, or factor VIII deficiency, is the most common form of hemophilia. In its severe form, patients have less than 1% of the normal amount of factor VIII, a blood protein necessary for blood to clot. The current treatment for hemophilia A is to inject factor VIII proteins directly into the patient’s bloodstream. Because they are foreign to the body, the immune system can respond to the factor VIII proteins as invaders that must be destroyed. When this happens, the immune system forms neutralizing antibodies called inhibitors. The inhibitors make hemophilia even more expensive and difficult to treat.  According to the CDC, 15 to 20% of people with hemophilia will develop an inhibitor.

In September 2015, the U.S. Food and Drug Administration announced that it had granted breakthrough therapy designation to a new medicine, ACE910, for the prophylactic treatment of people who are 12 years or older with hemophilia A with factor VIII inhibitors. Prophylactic treatment means they take the medicine regularly to prevent bleeding. Breakthrough therapy designation is designed to speed up the development of medicines that show great promise in improving treatment for serious diseases.

ACE910 is being developed by Genentech. It is not a factor concentrate – it doesn’t contain factor VIII proteins. Instead, it is an antibody that can perform the job of factor VIII, which is to make factor IXa better able to activate factor X.  ACE910 binds factor IXa and X, bringing them closer together so that the clotting process can continue and bleeding can be stopped. It doesn’t have to be injected into a vein. ACE910 is injected under the skin once a week.

The Genentech researchers presented the results of their Phase I clinical trial at the annual meeting of the American Society of Hematology in December 2014. This first trial was conducted in Japan and included 18 patients with severe hemophilia A. Eleven of the patients had inhibitors to factor VIII. They were divided into three groups, with each group getting a different dose of the drug. They were given an injection of ACE910 under their skin once a week for twelve weeks. The primary purpose of a Phase I trial is to determine safety:  looking for any “adverse events” while taking the medicine. All of the adverse events reported by the patients were mild except for two which were classified as moderate: a report of a headache and an upper respiratory tract infection. One patient stopped taking ACE910 due to mild redness at the injection site. Very importantly, no patients reported the medicine causing dangerous blood clots.

In June 2015, the researchers presented the results of their observation of the patients after receiving from 5.6 to 18.5 months of treatment with ACE910. The adverse events continued to be mild to moderate. Three patients developed antibodies against ACE910, but there was no sign that this changed its effectiveness. No “thromboembolic” adverse events (bad blood clots) were reported, even when the patient was given factor VIII concentrate or bypass agents at the same time as ACE910.

The researchers also presented information about the effectiveness of ACE910. They compared each patient’s “annualized bleeding rate” (ABR) for the six months before starting ACE910 to the rate after starting the drug. The Annualized Bleeding Rate is the number of bleeding episodes a patient has in a year. For periods of less than a year, it can be estimated by taking the number of bleeds in a month and multiplying by 12.

All of the patient groups experienced a decrease in their ABR after starting ACE910. The group receiving the lowest dose had a median decrease of 32.5 bleeds in a year to less than 2. Both the group with the middle dose and the one with the highest dose saw their median ABR drop to zero.  All groups included people with and without inhibitors to factor VIII.

Genentech has announced a goal of starting a Phase III clinical trial in patients with factor VIII inhibitors by the end of 2015 and a Phase III trial in patients without inhibitors in 2016. The hope is that ACE910 will prove to be a safe, effective treatment for hemophilia A that can be more easily given than infusions of factor concentrate.