While a host of companies are racing to treat hemophilia with cutting-edge gene therapies, others are working on nearer-term improvements to more conventional approaches, with billion-dollar franchises at stake. Genentech hopes to enter the hemophilia fray and announced Monday that its experimental drug emicizumab reduced bleeding by 87 percent, according to preliminary Phase 3 data.
Genentech, the South San Francisco, CA-based subsidiary of Swiss pharma giant Roche, has been testing emicizumab in hemophilia A patients enrolled in two Phase 3 trials dubbed HAVEN 1 and HAVEN 2. The drug is meant to be self-injected once a week as a preventive measure, or prophylaxis, not when a patient is having a bleeding episode. Genentech’s proposition is to reduce the amount of prophylaxis injections a patient requires.
These are the first data for HAVEN 1 since Genentech reported in December that the trial had met its main endpoint. But earlier this year Roche disclosed that a patient in the trial died of a hemorrhage, the latest in a series of serious complications affecting patients in the study. Roche had disclosed last November blood clotting complications in four patients in the trial. Two experienced thromboembolic events, in which a blood clot partly or completely obstructed a blood vessel. Two others experienced thrombotic microangiopathy, damage that affects the smallest blood vessels in the body’s organs.
Roche issued a statement to the European Haemophelia Consortium in Feburary that said an investigator concluded that the rectal hemorrhage that caused the patient death in HAVEN 1 was not related to emicizumab. In today’s announcement, Genentech says that the number of patients in the trial who experienced clotting complications now totals five—one additional patient experienced thrombotic microangiopathy. The company says the blood clotting complications were associated with repeated high doses of a treatment for breakthrough bleeds. The most common side effects experienced by patients included injection site reactions, headache, fatigue, upper respiratory tract infection, and joint pain.
Hemophilia A is caused by the deficiency of the blood-clotting protein called factor VIII. Patients not only bleed dangerously from cuts but also have smaller, regular internal bleeds that seep into tissues and joints and cause long-term damage.
Approximately 20,000 people in the U.S. and 400,000 worldwide are living with some form of hemophilia A, according to the Hemophilia Federation of America. It is far more common than hemophilia B.
Hemophilia can be treated with an infusion of the blood clotting proteins that patients lack. But patients can develop immune defenses against those infused proteins. When that happens, patients receive blood products that work by bypassing the clotting factors that are blocked by the immune defenses, called inhibitors. Genentech’s interim study results show that emicizumab handily beat bypassing agents.
Emicizumab is designed to restore coagulation by bringing together two clotting factors, IXa and X, which are needed to start the natural coagulation process. In the HAVEN 1 study, Genentech enrolled 109 adult and adolescent hemophilia A patients.
HAVEN 1 compared the Genentech drug to bypassing agents, with the main goal of reducing treated bleeds. By that measure, Genentech says the once-a-week injections reduced the bleeding rate by 87 percent. At a median observation point of 31 weeks, Genentech says 62.9 percent of patients treated with its drug had zero treated bleeds compared to 5.6 percent of patients who received bypassing agents. Genentech reported similar results for secondary goals; spontaneous bleeds and joint bleeds were reduced by 89 percent or better, the company says.
The Genentech drug is also showing promise as a potential treatment for children. Genentech says that interim results from HAVEN 2, which enrolled patients under 12, are consistent with the early results from HAVEN 1. After a median observation point of 12 weeks, one of the 19 patients on emicizumab reported a treated bleed. The company reported no joint or muscle bleeds. Genentech suggested that the dose used in adults is also appropriate for children.
Genentech has company in the hunt for new hemophilia treatments. Several biotechs are pursuing gene therapies that aim to insert the genetic instructions for producing blood clotting factors. Such treatments could be long lasting, perhaps even lifelong. But these treatments are also in earlier stages of development.
Genentech plans to present data from the two studies on July 10 at the International Society on Thrombosis and Haemostasis Meeting in Berlin, Germany.
Photo by Flickr user Joe Flintham via a Creative Commons license.
