Presentation Highlights

During yesterday’s State-of-the-Art Session, Steven Pipe, M.D. presented an overview of the current and future state of small molecules in the treatment of hemophilia. These new therapies are very exciting, as they represent a paradigm shift not seen since the advent of the first replacement products and prophylactic therapy:

  • There have been great advances in the development of treatments for people with hemophilia A, particularly those with inhibitors, and will only be supplanted by gene therapy once its challenges are overcome.
  • Clinical studies of three novel therapies that target the natural anticoagulant proteins that modulate hemostasis (i.e., tissue factor pathway inhibitor, antithrombin, protein C) are underway.

These therapies are transforming the lives of patients with hemophilia, particularly those with inhibitors, who have not had adequate treatment options in the past.


Patients with hemophilia A with inhibitors have not been adequately treated historically, but newer therapies are now able to transform the lives of these patients. Not since the late 1960’s and 70’s, when the first replacement products were introduced, has there been so much enthusiasm about new treatment products. The development of these novel molecules has initiated a venerable “arm’s race” between traditional and long-acting factors, non-IV therapies, and the development of gene therapies.

During his presentation, Pipe reiterated findings from the HAVEN 1 and HAVEN 2 phase 3 trials with emicizumab as a non-replacement therapy for the treatment of hemophilia A. He also described clinical studies of three novel therapies that target natural anticoagulant proteins that modulate hemostasis:

  • Tissue factor pathway inhibitor (TFPI)
  • Antithrombin
  • Protein C

These novel therapies may significantly reduce the burden of traditional, intravenously administered Factor VIII replacement for the treatment of hemophilia A, especially in patients with inhibitors. This marks a paradigm shift in the treatment of these patients. These agents can be administered subcutaneously, require less frequent dosing due to longer half-lives, and exhibit clinical efficacy as demonstrated in early clinical trial data. In some cases, these small molecule therapies may be considered pan-hemostatic, in that they have the potential to treat other clotting factor-based bleeding disorders. Notably, they are not impeded by anti-factor antibodies and do not trigger inhibitors to the missing protein (because the protein is not being replaced). Most importantly though, these novel agents have already been shown to transform the lives of patients with hemophilia A with inhibitors.

For hemophilia A patients who are not adequately treated with current therapies, particularly those with inhibitors, novel small molecule therapies may raise the bar for care to overcome the remaining complications of traditional hemophilia therapies.

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