ASH 2024 | The current approaches to prophylaxis in hemophilia and tailoring treatment to the individual

The current approaches to prophylaxis and hemophilia vary based upon the type of hemophilia you have, your age, and patient preference. Of course, we all know that prophylaxis is best for patients with severe hemophilia to suppress or prevent bleeding episodes. We also know that many patients with moderate hemophilia may also have a more severe bleeding phenotype and should be considered for prophylaxis. Beyond the severe bleeding phenotype, patients with moderate hemophilia may be left behind due to their levels in terms of their ability to participate in normal activity and sports, and therefore those discussions should be held for prophylaxis as well.

For factor VIII deficiency, we have a number of options for prophylaxis. For utilizing factor VIII concentrates, there is a new therapy that was licensed within the last two years, I believe, that breaks the barrier, the ceiling barrier of von Willebrand factor binding barrier, and extends the half-life of factor VIII, allowing once-weekly administration, which is truly a breakthrough for factor VIII therapy. Its residual trough levels are very adequate for control of hemostasis, and many patients remain within the normal range for approximately four to five days, depending upon their individual pharmacokinetics. 

There are also novel therapies, which are non-factor therapies, such as emicizumab, which binds factor IXa and X and can be used and administered subcutaneously for administration of prophylaxis. These give you a steady state factor VIII level or conferred level is somewhere in the mild range. However, if breakthrough bleeding does occur, a factor VIII concentrate would have to be used for patients who don’t have an inhibitor or bypassing therapy would need to be utilized for patients with an inhibitor. The bypassing agent of choice would be a recombinant factor VIIa as the use of an APC concentrate has been known to be associated with development of thrombosis and a microangiopathic process. This molecule has been a breakthrough for patients with factor VIII with an inhibitor in terms of providing really excellent prophylaxis, which we were not able to do before. 

In terms of factor IX deficiency without an inhibitor, we have a variety of factor IX concentrates that are longer lasting. There are a variety of mechanisms that are utilized to extend the half-life, including pegylation, Fc fusion, albumin fusion, etc. So the decision of which of these to utilize is based upon a discussion with the patient, patient preference, review of data, and safety. It is very difficult in a young patient, say less than a year of age, to start prophylaxis with factor IX concentrate. Therefore, either prophylaxis can be delayed in those patients, which may put them at risk of bleeding, or you may start early and have to utilize an inserted central venous access device. As opposed to infants with severe factor VIII deficiency may start, for example, emicizumab in the newborn period and be protected against bleeding even during that period of time when venous access is not accessible for administration of factor VIII therapy at home. And it saves them from the use of a central venous access device. 

So there are a variety of things that we can utilize for prophylaxis. These methods for prophylaxis, again, don’t just apply to patients with severe disease. They also apply to patients with moderate disease and some patients with mild disease who participate in very strenuous activities or have individual life goals that require them to have higher levels.

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