Exploring Factor VIII Replacement Therapies: A Guide to Choosing the Right Treatment for Patients With Hemophilia A

Author: Sanofi

Sanofi

Ensuring optimal care for patients with hemophilia A requires a thorough understanding of available treatment options, prioritization of bleed prevention and long-term joint health, and comprehensive patient education. This article will cover different types of factor VIII replacement therapies^* and will compare an on-demand versus prophylactic treatment approach with the goal of helping tailor treatment plans effectively, which can help enhance quality of life.

^*Factor-replacement therapy is one class of treatment option for hemophilia patients. This article does not examine factor mimetic, gene therapy, or investigational treatments.

Hemophilia A Treatments: Prophylaxis vs On-Demand

Prophylaxis treatment is recognized by the World Federation of Hemophilia (WFH) Guidelines for the Management of Hemophilia as the standard of care for individuals with severe hemophilia, and for some with moderate hemophilia. The WFH Guidelines recommend starting prophylaxis before the age of 3 years to help prevent musculoskeletal complications due to recurrent joint and muscle bleeds.

Individualized dosing regimens are tailored to a patient's lifestyle, physical activity level, and pharmacokinetics, ensuring that each patient receives the correct dose to maintain their target factor VIII level while minimizing the risk of bleeds.

On-demand treatment is useful for managing acute bleeds, but doesn’t offer the same level of protection as prophylaxis and may lead to more frequent and severe bleeding episodes in the long run. The WFH Guidelines advise that on-demand factor replacement should no longer be considered a long-term treatment option since it’s only a response to a bleed—prevention of bleeds and long-term joint damage should be the priority for patients and their doctors.

Types of Factor VIII Replacement Therapies, Infusion Rates, and Dosing Frequency

Maintaining adequate factor VIII trough levels is crucial in hemophilia A management to ensure continuous protection against spontaneous bleeding, especially for patients on prophylactic treatment. Previously, experts considered a trough factor level of 1 IU/dL (1%) adequate, but current standards recommend significantly higher levels (>3%-5% or higher).

Standard half-life (SHL) factor VIII infusions have a half-life of approximately 12 hours in adults. The short half-life of SHLs results in the need for frequent infusions. On average, this is 3 infusions per week for patients to maintain minimal trough levels (>1%). Because of higher clearance rates, half-life is shorter in individuals younger than 18 years, which may result in requiring more frequent infusions that many patients are unwilling or unable to do. Conventional factor prophylaxis with SHLs is classified by intensity: high-dose (25-40 IU/kg every 2 days), intermediate-dose (15-25 IU/kg 3 days per week), and low-dose (10-15 IU/kg 2-3 days per week).

Extended half-life (EHL) factor VIII infusions have a half-life that is 1.4-1.6–fold longer than SHL products. However, the half-life of EHLs is still limited to up to 19 hours.

While EHLs require less frequent administration than SHL therapy, patients may still require 2 or more infusions per week to maintain desired trough levels. The criteria for high-, intermediate-, and low-dose prophylaxis with EHLs are not yet established, and these definitions may require revision due to the differing pharmacokinetic profiles of SHLs and EHLs.

High-sustained factor (HSF) therapy was designed to extend half-life longer than EHLs (~19 hours) and SHLs (~12 hours), allowing for less-frequent administration.

Hemophilia home-infusion therapy allows people to self-infuse from the comfort of home. The WFH recommends providing adequate education to the person with hemophilia, as well as a family member or caregiver. This includes learning the factor VIII replacement calculation, understanding the factor VIII replacement formula so they are using an accurate and safe dose every time, and learning to recognize potential complications.

The rate of infusion and frequency of dosing are dependent on an individual’s specific needs. Several factors can impact these, including the patient’s weight, severity of bleeding, and level of comfort with treatment. These decisions are made at the discretion of the healthcare provider, who will consider all relevant factors to ensure optimal treatment that is tailored to the lifestyle and goals of each patient.

The frequency of dosing depends on whether a patient is using a prophylaxis treatment or on-demand therapy and whether the factor VIII replacement therapy is a standard half-life, extended half-life, or high-sustained factor therapy.

Switching Treatments for Hemophilia A Patients

With newer treatments, it is now possible to aim for higher factor VIII levels. Doctors should ensure patients understand that achieving higher trough levels may require higher doses or more frequent infusions with SHL and EHL therapies.

Potential Complications of Factor VIII Infusion

For Hemophilia Patients With Inhibitors

One of the most significant complications that should be considered with factor VIII replacement therapies is the development of inhibitors—antibodies that neutralize the effectiveness of the replacement clotting factor. According to WFH Guidelines, patients who develop inhibitors should have access to appropriate hemostatic agents for bleeding control and surgical interventions, if needed, at experienced centers.

Bypassing agents and other non-factor treatment products may be an option for patients with inhibitors. These treatments can provide effective hemostasis and help manage bleeding episodes effectively.

Conclusion

Involving patients in developing personalized treatment plans for hemophilia A is essential. By educating patients on their factor VIII activity and different treatment options, healthcare providers can set individualized and achievable goals. This collaborative approach may enhance adherence to treatment, reduce bleeding episodes, and improve overall quality of life. Engaging patients in their care not only fosters better health outcomes, but also strengthens the patient–provider relationship, ultimately leading to more effective hemophilia A management.

Learn more about a potential treatment option for your patients.

References

1. Srivastava A, et al. Haemophilia. 2020;26(suppl 6):1-158. 2. Shared decision making tool: Clotting factor replacement therapies. World Federation of Hemophilia. Updated March 2024. Accessed July 25, 2024. https://www1.wfh.org/publications/files/pdf-2365.pdf 3. Malec L, et al. Haemophilia. 2023;29(6):1419-1429. 4. Von Drygalski A, et al. N Engl J Med. 2023;388(4):310-318.

MAT-US-2407200-v1.0-09/2024