Past, Present, and Future of Hemophilia Care

Despite affecting only about 20,000 people, hemophilia ranks as one of the most expensive chronic diseases in the United States, with treatment costs as high as $1 million per year for patients who develop complications. Advances in diagnosis and treatment over the past two decades have transformed hemophilia from a fatal condition to a manageable chronic disease. This year’s Specialty Connect focused on hemophilia, with discussions including clinical and economic complexities, as well as new and developing therapeutics. Steven W. Pipe, MD, of the University of Michigan in Ann Arbor, kicked off the meeting by discussing the latest in hemophilia care.

The current treatment landscape includes a widespread availability of safe and effective factor VIII (FVIII) and factor IX (FIX) therapies. Prophylaxis is important to prevent bleeds and joint damage, and even tertiary prophylaxis in older and previously-treated patients with joint damage can result in an improvement in health-related quality of life and maintained mobility. Prophylaxis therapy has been used in the United States for 25 to 30 years now, but now the hemophilia space is on the verge of non-replacement therapy and gene therapy. Dr. Pipe noted that one of the challenges is treating patients with inhibitors, a group that represent approximately 30% of patients with very limited treatment options.

Another promising treatment option is extended half-life (EHL) agents that provide much better control of joint bleeds. “I think our patients have been satisfied with switches [to these therapies],” he said. EHL factors have helped with non-adherence, new-onset target joint bleeding, pharmacokinetic tailoring of prophylaxis, immune tolerance induction, and reduction in burden of prophylaxis. However, these agents come at a premium. “We have a responsibility to document that these [agents] are worth the increased price,” said Dr. Pipe. In addition, determining the proper FVIII trough level to provide adequate bleeding prevention varies widely, based on factors such as patient age and activity level.

Despite the treatment advances that have been made, there are still unmet needs for patients with hemophilia A, including:

  • There is an attraction for once-weekly dosing for some patients, particularly for those with moderate or mild severity who require prophylaxis
  • Inhibitor prevention remains the highest priority
  • Inhibitor eradication may be higher with EHLs
  • There is a need to show improved outcomes with EHLs to justify price

A new area where treatment options are arising is non-replacement therapy, and one agent has been approved to date: emicizumab, a humanized monoclonal antibody for the treatment of hemophilia A in patients with and without inhibitors. “This is the first therapy [that] doesn’t care if the patient has an inhibitor or not,” he said. The approval was based on results from the HAVEN trials. In HAVEN 1, emicizumab reduced treated bleeds by 87% compared with no prophylaxis.

Other therapeutic agents in development include:

  • A phase II open-label, extension study showed that the anti-tissue factor pathway inhibitor fitusiran resulted in 48% of patients remaining bleed-free during observation.
  • Protein C is a common mutation in factor V molecule, which is a risk factor for venous thrombosis, and protein C inhibitors could lead to proteolytic degradation of factor Va.
  • A promising gene therapy, in which clinical trials have led to levels in the “curative” range for FVIII and FIX.

“In the next two to five years, I’m confident that some kind of gene therapy [for hemophilia] will come to our clinics,” he said.

“My goal for patients is to get to zero bleeds,” Dr. Pipe concluded. “We can achieve this, and hopefully some of the therapies discussed [today] will get us there.”

Presentation: The Present and Future of Hemophilia Treatment. AMCP Annual Meeting 2018 Specialty Connect.