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Hemophilia Care: Non-Factor Therapies
Shifting the Paradigm in Hemophilia Care: Practical Insights Into Integrating Non-Factor Therapies

Released: May 16, 2025

Expiration: May 16, 2026

Justin Arnall
Justin Arnall, PharmD, FCCP, BCOP
Guy Young
Guy Young, MD
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Key Takeaways
  • Non-factor therapies provide effective prophylaxis for patients with hemophilia A and B, offering substantial benefits in convenience and improving adherence.
  • Pharmacists play a vital role in patient education, drug access, and therapy management, especially as new agents with distinct monitoring and operational requirements become available.
  • Optimal outcomes depend on individualized therapy selection and multidisciplinary collaboration, including ongoing coordination with hemophilia treatment centers.

Introduction
As the treatment landscape for hemophilia continues to evolve, non-factor therapies have emerged as a transformative option for both hemophilia A and B, with or without inhibitors. These therapies not only provide effective bleed prevention but also reduce treatment burden and open new doors for individualized care.

Redefining Hemostasis: Where We’ve Been and Where We’re Headed
Over the past decade, hemophilia treatment has shifted from intensive intravenous factor replacement to innovative subcutaneous therapies that mimic or rebalance coagulation pathways. This evolution is particularly significant for patients with limited venous access, adherence challenges, or high treatment burden. Extended half-life factor products provided the first step forward, but it is the rise of non-factor therapies—like the recently approved agents emicizumab, marstacimab, concizumab, and fitusiran, as well as investigational agents such as Mim8—that has dramatically reshaped our management approach.

What we now see is an opportunity to personalize prophylaxis not only by bleed risk or inhibitor status but also by patient lifestyle, age, comorbidities, and psychosocial factors. As such, healthcare professionals (HCPs) must be equipped not just with a deep understanding of these therapies but also with systems and strategies to implement them effectively.

Non-Factor Agents: Understanding the Clinical Options
Emicizumab, the longest-standing non-factor agent, is a bispecific antibody that acts as a bridge between activated factor IX and factor X to facilitate blood clots and has demonstrated consistent efficacy in reducing annualized bleeding rates across all age groups and inhibitor statuses. It is approved by the FDA as routine prophylaxis to prevent or reduce frequency of bleeding episodes in adult and pediatric patients (newborn or older) with hemophilia A with or without FVIII inhibitors. Emicizumab offers flexible dosing regimens (weekly to monthly) and is generally well-tolerated. Its most notable safety consideration is the risk of thrombotic events when used with activated prothrombin complex concentrates, a risk now mitigated by clear administration guidelines.

Concizumab and marstacimab are both monoclonal antibodies that target tissue factor pathway inhibitor to help achieve homeostasis in the coagulation cascade. Concizumab is indicated for patients 12 years of age or older with hemophilia A or B with inhibitors and is administered as a once-daily, weight-based subcutaneous injection. It also has a unique monitoring protocol after approximately 28 days of therapy to determine the plasma concentration of concizumab and allow for dose adjustments to minimize thrombotic risk. Marstacimab is approved for patients 12 years of age or older with hemophilia A or B without inhibitors and is administered weekly as a flat-dose subcutaneous injection. Marstacimab does not require specific lab monitoring protocols, but as with any non-factor replacement therapy and rebalancing agent, regular monitoring for signs and symptoms of thrombosis is essential.

Fitusiran is an antithrombin-directed siRNA therapy approved by the FDA on March 28, 2025, for patients aged 12 years or older with hemophilia A or B, with or without factor VIII or IX inhibitors. Administered subcutaneously, fitusiran offers a dosing regimen of 50 mg every 2 months, with adjustments based on antithrombin activity levels, which should be monitored a Weeks 4, 12, 20, and 24 after the starting dose and after any dose modification. The prescribing information for fitusiran includes a boxed warning for thrombotic events as well as for acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis. To mitigate these risks, it is recommended to carefully monitor antithrombin activity and monitor for signs and symptoms of thrombotic events as well as for signs and symptoms of acute and recurrent gallbladder disease.

Tailoring Therapy: Moving Beyond A One-Size-Fits-All Approach
Hemophilia care is no longer constrained to a fixed regimen; instead, it can—and should—be adjusted based on patient- and practice-specific real-world variables.

For example, athletes or patients engaging in high-risk activities may benefit from factor-based prophylaxis to allow for activity-related “topping up,” while others with stable lifestyles may find monthly subcutaneous therapy more appealing. Some patients also prefer once daily dosing so they have an easy to remember routine while other patients may prefer less frequent injections and be willing to set weekly or monthly reminders. Of importance, in young children or patients with significant venous access challenges, the ease of subcutaneous administration may become a primary consideration.

Patient age is also a key factor. Adolescents and young adults often experience decreased adherence as they transition to self-managed care. The flexibility of non-factor therapies may help bridge this gap, but we must remain vigilant and proactive in assessing and supporting medication adherence. Older adults, on the other hand, bring new challenges, including age-related comorbidities that may influence thrombosis risk and overall treatment goals.

The Pharmacist’s Role: Bridging Logistics, Education, and Patient Support
As non-factor therapies enter broader clinical use, pharmacists—especially those in specialty and hospital settings—play a critical role in their implementation and optimization.

These agents present new operational considerations, from managing unique storage requirements and coordinating dose rounding for weight-based agents like emicizumab, to understanding prefilled delivery devices (pens or syringes) and ensuring access to necessary supplies like filter and pen needles. Pharmacists must also be well-versed in navigating insurance authorizations, which may be impacted by inhibitor status, patient age, and FDA-approved indications.

Perhaps more importantly, pharmacists are central to patient education. For therapies like concizumab and marstacimab, injection technique, dose timing, and missed dose protocols must be clearly explained and reinforced. When products require lab monitoring—such as concizumab plasma levels or antithrombin assays with fitusiran—pharmacists can coordinate testing logistics and help interpret results in collaboration with clinical care teams. Pharmacists also play a key role in patient education—clarifying the purpose of lab monitoring and how results guide treatment. They can further support patients by developing and communicating individualized breakthrough bleeding plans, ensuring readiness to manage unexpected episodes.

Pharmacists also serve as accessible points of contact for patients, particularly in troubleshooting administration issues or managing adverse events like injection-site reactions. Given the variability in monitoring needs and pharmacokinetics across these agents, pharmacists are in a unique position to personalize adherence support strategies, whether that means weekly check-ins, refill reminders, or proactive assessment of supply usage.

The Ongoing Role of Comprehensive Care
Even as hemophilia treatment advances lead to more efficacious and safer options—and as administration and dosing become more convenient—the need for multidisciplinary, specialized care remains of paramount importance. Hemophilia treatment centers (HTCs) continue to provide essential services, from physical therapy and psychosocial support, to factor stewardship and access to clinical trial enrollment.

Moreover, the role of HTCs will likely expand as more non-factor agents are approved. It is crucial that care coordination between local HCPs, specialty pharmacies, and HTCs remains strong to avoid fragmented care and ensure optimal patient outcomes. Internal systems should adopt or adapt factor stewardship models to include non-factor therapies, ensuring appropriate usage, safety, and cost-effectiveness.

Summary
We are in a new era of hemophilia care, in which we can meaningfully tailor therapy to match patient needs and lifestyles, reduce treatment burden, and improve outcomes across a diverse patient population. The integration of non-factor therapies empowers HCPs with more tools than ever before. However, with this comes the responsibility to stay informed, coordinate care effectively, and engage patients in shared decision-making.

Your Thoughts
How is your clinic preparing for the increased use of non-factor therapies? What roles are your pharmacists playing in patient support and therapeutic education? We’d love to hear how your team is adapting to the future of hemophilia care.

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How often do you discuss the purpose and importance of lab monitoring with patients to support their understanding and engagement in care?

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