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Advancing Hemophilia Management
Advancing Hemophilia Management—Practical Insights for Clinicians

Released: March 18, 2025

Expiration: March 17, 2026

Mark T Reding
Mark T Reding, MD
Guy Young
Guy Young, MD
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Key Takeaways
  • Personalized Treatment is Essential: Consider patient preferences, lifestyle, and bleeding phenotype when selecting therapies.
  • Efanesoctocog Alfa for Active Patients: This novel extended half-life therapy offers increased bleed protection with fewer infusions and may be a good option for athletes and highly active individuals.
  • Non-Factor Therapies Offer Convenience: Emicizumab, concizumab, and marstacimab provide subcutaneous options for specific patient populations seeking alternatives to IV infusions.

Historically, the primary goal of hemophilia management was to prevent life-threatening bleeds and reduce long-term complications such as joint damage or hemarthrosis. However, the treatment paradigm has shifted from merely surviving to thriving by achieving near-normal hemostasis, which allows patients to lead less restricted lives. A multidisciplinary approach and access to specialized hemophilia treatment centers are key to achieving the best outcomes for our patients​. As we learn more about this disease and novel treatment options continue to be approved, patients with hemophilia will benefit from tailored management strategies.

Individualizing Therapy: The Role of Extended Half-Life Products and Novel Agents
Recent advances have introduced extended half-life factor VIII and IX replacement therapies, which allow for reduced infusion frequency without compromising efficacy. Efanesoctocog alfa is a novel factor VIII fusion protein with an ultra-extended half-life that was approved by the FDA in 2023 for routine prophylaxis and on-demand treatment to control bleeding episodes and perioperative management for adults and children with hemophilia A. By overcoming the von Willebrand factor half-life ceiling, it provides extended protection from bleeds, maintaining factor VIII levels at normal or near normal range for 4 days post administration​.

In both adolescents and adults, efanesoctocog alfa demonstrated higher trough levels and superior bleed protection vs prestudy recombinant or plasma-derived factor VIII prophylaxis in the phase III XTEND-1 trial, making it a good option, particularly for those with an active lifestyle or recurrent hemarthrosis though it is an option for prophylaxis for all hemophilia A patients. This treatment approach reduces infusion frequency and alleviates treatment burden, while also protecting against spontaneous and traumatic bleeding events.

Non-Factor Replacement Therapies: A New Frontier
Although factor replacement remains central to hemophilia management, non-factor replacement therapies have revolutionized care for patients with inhibitors as well as being an excellent option for those with challenging venous access or just those seeking more convenience. Emicizumab, a bispecific antibody that mimics factor VIII activity, is FDA approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients (newborn or older) with hemophilia A with or without factor VIII inhibitors. Emicizumab offers convenient, subcutaneous administration and can be given once weekly, once every 2 weeks, or once every 4 weeks. Emicizumab provides factor VIII-equivalent activity levels akin to mild hemophilia, with approximately 55% to 65% of patients experiencing no treated bleeds over 24 weeks in the clinical trials.

Concizumab, a tissue factor pathway inhibitor (TFPI) antagonist, is FDA approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A or B with inhibitors. Concizumab is administered as a once-daily, weight-based subcutaneous injection via a pen injector, which can potentially improve adherence and quality of life for patients. In the explorer7 trial, concizumab resulted in an 86% reduction in estimated mean annualized bleed rate (ABR) with 64% of patients experiencing no treated bleeds at 24 weeks. However, effective management requires measuring plasma concentrations of concizumab 4 weeks after starting therapy to optimize maintenance dosing as well as reducing the risk for thromboembolic events.

Marstacimab is an anti-TFPI monoclonal antibody that is FDA approved for routine prophylaxis to prevent or reduce bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A or B without inhibitors. Marstacimab is administered as a once-weekly, flat-dose subcutaneous injection, which should be administered on the same day each week. Routine prophylaxis with marstacimab resulted in a 35% reduction in ABR compared with factor prophylaxis, with an estimated mean ABR of 5.6% during the active treatment stage with marstacimab in the BASIS trial. Marstacimab does not require monitoring of plasma concentration levels, but as with any non-factor replacement therapy and rebalancing agent, regular monitoring for signs and symptoms of thrombosis is essential.

Gene Therapy: A Glimpse Into the Future
Gene therapy represents a potential breakthrough for hemophilia A and B, with 2 different options currently FDA approved. Etranacogene dezaparvovec is approved for a   dults with hemophilia B who currently use FIX prophylaxis or have current or historical life-threatening hemorrhage or repeated, serious spontaneous bleeding episodes. Valoctocogene roxaparvovec is approved for adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity <1 IU/dL) without preexisting antibodies to AAV-5.

Although uptake of gene therapy for hemophilia remains low due to cost, insurance barriers, and long-term efficacy concerns, data from trials like the phase III HOPE-B study of etranacogene dezaparvovec for hemophilia B suggest that gene therapy could provide sustained endogenous factor production, reducing or eliminating the need for regular infusions​.

Although gene therapy is not yet a widespread solution, it holds the potential to transform hemophilia care, particularly for patients with adherence challenges or those seeking a one-time treatment option​.

Practical Considerations: Laboratory Monitoring and Cost Management
An often-overlooked aspect of incorporating new therapies for patients with hemophilia is the need for laboratory monitoring. Traditionally, monitoring the response to FVIII concentrate and inhibitor titer has been recommended. However, with these newer treatment options, laboratory monitoring is either impossible or challenging. For example, assays such as chromogenic factor VIII assay or a diagnostic assay with specific emicizumab calibrator plasma could be used in patients receiving emicizumab to determine the approximate level of the drug. Furthermore, a bovine chromogenic FVIII assay is required to assess FVIII levels (if/when needed) in patients on emicizumab since traditional one-stage assays give false results. As mentioned earlier, plasma concentrations need to be monitored in patients receiving concizumab at least once at 4 weeks after treatment initiation. Healthcare professionals should maintain close communication with laboratory teams to ensure accurate monitoring and appropriate adjustments based on the patient’s treatment plan.

In addition, with the rising costs of newer therapies, financial considerations are critical. Programs like patient assistance programs can help improve access for individuals with insurance coverage challenges​​. Although gene therapies come with high upfront costs, analyses suggest potential long-term savings by reducing the need for ongoing prophylaxis.

Toward Personalized Hemophilia Management
The evolving landscape of hemophilia care offers unprecedented opportunities for improved outcomes and quality of life. Key advances in extended half-life factor therapies, non-factor replacement agents including FVIII mimetics and anti-TFPIs, as well as gene therapy have expanded the range of options available to healthcare professionals and patients. However, individualized care remains the cornerstone of optimal treatment.

Your Thoughts?
How are you integrating new hemophilia therapies into your clinical practice? Have you encountered any challenges with patient access or insurance coverage? Share your experiences and thoughts as collaboration and shared knowledge will drive the next wave of advancements in hemophilia care.

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Which of the following novel therapies have you prescribed to your patients with hemophilia?

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