Efficacy, Approval, and Personal Experience with Emicizumab

Meera B. Chitlur, MD: Emicizumab is a monoclonal humanized recombinant bispecific antibody that is able to substitute factor VIII. Essentially, what emicizumab does is connect activated factor IX with factor X, thereby allowing the clotting process to proceed as if factor VIII was present in the system. Factor VIII works as a cofactor, and emicizumab compensates for this cofactor activity.

It is important to remember that emicizumab can only substitute factor VIII, not any of the other clotting proteins. It can only be used for hemophilia A, not for hemophilia B.

Factor VIII and emicizumab are different proteins, and the differences are as follows. Factor VIII needs to be activated, whereas emicizumab does not. Factor VIII has multiple sites of binding on the clotting protein cascade, whereas emicizumab has only 1 site of binding. Factor VIII binds to von Willebrand factor, whereas emicizumab does not. Factor VIII also binds to phospholipid surfaces as well as the activated platelet, whereas emicizumab does not. Factor VIII activation physiologically results in 10-times increased generation of thrombin, whereas emicizumab is not as effective. Emicizumab can bind to both activated and nonactivated factor IX and X, whereas factor VIII can only bind to activated factor IX.

My personal experience with emicizumab is that we participated in the studies. The studies were open at our center and our patients were part of these studies, so we have had the opportunity to witness what the efficacy and safety was with this product in our patients. The advantage of emicizumab is the fact that it can be administered subcutaneously and that its half-life is extremely long. Both of these are a significant advantage in the pediatric group because the frequency of administration makes it very difficult, especially given intravenously, for that patient population. Subcutaneous administration makes this significantly better in that patients and parents do not have to be taught how to access a vein. Subcutaneous administration, once weekly or once monthly, is a significant improvement over the every 2- or 3-day schedules that we were using previously for our patients. Emicizumab offers these 2 primary advantages to our patient population.

Emicizumab has been approved in all patients with hemophilia A, with or without inhibitors and of any severity, which means that all patients with hemophilia A are eligible for this product. In addition to the decreased frequency of administration and the subcutaneous administration, it’s also important to make sure that the product is efficacious. In the studies with emicizumab, we have been able to demonstrate that it was extremely efficacious for inhibitor as well as noninhibitor patients in that bleeding frequency was decreased dramatically in both populations.

I think emicizumab will truly change the treatment paradigm for patients with hemophilia A in that we are able to use this prophylactically for prevention of bleeding. The one important thing that we have to remember is that it doesn’t normalize coagulation in these patients. Therefore, we are still unsure of exactly how we can utilize this in certain populations of patients, especially those who are very active or who play competitive sports. But for the normal run-of-the-mill patient who is noncompliant, who potentially does not want to treat very frequently, or who is not extremely active, this would be an ideal prophylactic method of treatment. We are able to use it on a weekly basis, and in many patients, maybe a monthly basis. For adults who are not excessively active, this is a marvelous, remarkable treatment option in that they are able to administer it weekly or monthly and still not experience any significant bleeding.

In spite of this, we have to remember that breakthrough bleeding can occur in these patients. There will be a need for regular product to be used for treatment of breakthrough bleeds in these patients. I anticipate that most patients will go on prophylaxis with emicizumab, and breakthrough bleeds will then be treated with recombinant or plasma-derived factor concentrates.

The number of doses that might be required for treatment of breakthrough bleeds may be significantly decreased since most patients will be converted to a milder phenotype. Even if you have severe hemophilia, you are potentially going to be treated like somebody who has mild hemophilia A. Therefore, very small bleeds or very minor bleeds may not actually even require treatment. Only major or significant trauma will need to be treated.

It is important to remember that patients should be able to recognize and identify what is a major or nonmajor bleed. Education will still be needed for these patients to ensure that they can identify bleeds that require treatment immediately or identify bleeds that are minor, where they could potentially wait and see if treatment is required.

Practice with venous access is the other factor that I think about. As patients go on subcutaneous treatment and get treated once or twice a week or month, will they forget how to access their veins if they don’t have as many bleeding complications? Will they need to come to the emergency department or hospital for every bleed because they no longer know how to access their veins and receive treatment at home? Will this potentially result in a delay in treatment? This is the other thing we need to think about. But I anticipate and hope that patients will still maintain their venous access proficiency and will be able to treat at home appropriately if needed. These are things that we’ll learn as we move forward.

Cost is a concern, but we anticipate that because the frequency of bleeding is going to be significantly decreased, the cost will potentially be absorbed into that. Compared to a 2- or 3-times weekly treatment with regular factor products, if I’m treating once a week or once a month, the cost will potentially be equated there.

Transcript edited for clarity.