It is an exciting time in the treatment of people with bleeding disorders with many coagulation products having been recently approved by Health Canada or “in the pipeline” at various stages of clinical research. So many treatments, in fact, that it has become difficult to keep track of them all. To help everyone stay informed of their progress through clinical trials and regulatory approval, the CHS publishes four charts, one each for …
non-factor coagulation products that may prove efficacious in both inhibitor and non-inhibitor patients; and
While some of these are still in early phase 1 or 2 stages in the research process and several years away entering the market, others are in phase 3 trials, the final stage before an application is made to market the product commercially.(Types of clinical trials)
Extended half-life products
The development of extended half-life products was the first major improvement in care for hemophilia since the advent of virally safe concentrates and prophylaxis in the late 1980s.The half-life of factor IX is extended 2.5 to 5 times, factor VIII 1.5 times and recombinant factor VIIa possibly eight-fold. This has the potential to reduce the frequency of infusions, leading to increased adherence, or increase the trough levels in prophylaxis, a clear advance in efficacy.
More potent products/Novel mechanisms of action
Some of the products in development are designed to be more potent and more efficacious in stopping bleeding or to be based on entirely novel mechanisms of action, for example:
- monoclonal antibodies that mimic factor VIII, injected subcutaneously;
- monoclonal antibodies that reduce tissue factor pathway inhibitors, injected subcutaneously;
- fitusiran, an RNA interference (RNAi) therapeutic that reduces levels of antithrombin, injected subcutaneously.
These developmemts are critically important for patients with inhibitors, for whom current treatments are not nearly as effective as conventional treatments for patients with hemophilia A and B without inhibitors.
Broader portfolios for companies
The pipeline sees the development of broader portfolios for companies so that they can market products in all major areas—hemophilia A, hemophilia B, von Willebrand disease and inhibitors—and not just one or two. This has the potential to increase world supply and competition. In a worldwide market growing by 8% a year, this is a good thing.
While not all of these products will make it to market, many are very promising. We update these charts periodically; we invite you to consult this page regularly to follow progress.
In the last several years, Health Canada has approved 14 new products:
- Alprolix, an extended half-life recombinant factor IX manufactured by Sanofi, in March 2014;
- Eloctate, an extended half-life recombinant factor VIII manufactured by Sanofi, in August 2014;
- Rixubis, a standard half-life recombinant factor IX manufactured by Takeda, in September 2014;
- Nuwiq, a standard half-life recombinant FVIII product manufactured by Octapharma, using a human cell line in November 2014;
- Zonovate, a standard half-life recombinant factor VIII manufactured by Novo Nordisk, in January 2015;
- Kovaltry, a standard half-life recombinant factor VIII manufactured by Bayer, in January 2016;
- Idelvion, an extended half-life recombinant factor IX manufactured by CSL Behring, in January 2016;
- Adynovate, a pegylated extended half-life recombinant factor VIII manufactured by Tekada, in November 2017;
- Rebinyn, a pegylated extended half-life recombinant factor IX manufactured by Novo Nordisk, in November 2017
- Afstyla, a standard half-life recombinant factor VIII manufactured by CSL Behring, in January 2018;
- Jivi, a pegylated extended half-life recombinant factor VIII manufactured by Bayer, in October 2018
- Vonvendi, a recombinant von Willebrand factor manufactured by Takeda, in January 2019;
- Esperoct, a pegylated extended half-life recombinant factor VIII manufactured by Novo Nordisk, in July 2019.
In addition, the first non-factor replacement therapy, Hemlibra, a monoclonal antibody that mimics factor VIII, was approved for people with hemophilia A and an inhibitor in August 2018, and for all people with hemophilia A in June 2019.
Many of these products have been approved for distribution by Canadian Blood Services and/or Héma-Québec. For more information, see www.hemophilia.ca/coagulation-products.