Long-acting therapies reshape hemophilia care beyond bleeding prevention < Hospital < Article

Treatment for hemophilia A is no longer limited to responding to bleeding episodes as they occur.

To minimize recurrent joint bleeds and the resulting joint damage, the core focus of treatment has already shifted to “prophylactic therapy.” It is now entering an era of “personalized treatment,” tailored to each patient’s bleeding patterns and lifestyle.

In particular, the advent of long-acting formulations that maintain stable clotting factor levels with just one weekly dose is emerging as a turning point, with the potential to fundamentally improve the quality of life for hemophilia patients.

Korea Biomedical Review met with Professors Han Jung-woo, Hahn Seung-min, and An Won-ki of Yonsei Cancer Hospital to discuss the changing paradigm in hemophilia A treatment, challenges in the clinical setting, and the future treatment environment that needs to be established.

KBR: What is the most significant difficulty faced by hemophilia A patients? How much does bleeding impact their quality of life?

Professor An Won-ki (AWK): Hemophilia is not simply a disease where blood doesn’t clot easily. It’s a condition where bleeding imposes persistent limitations on all aspects of a patient’s life. Recurrent joint bleeds and the resulting joint damage are the most significant burden for patients. Many patients live with a constant fear — “Will moving like this cause pain again?” — which often leads to withdrawal from school or work life and, ultimately, emotional distress as patients impose restrictions on themselves.

KBR: How does recurrent bleeding during childhood and adolescence affect joint function after growth?

AWK: Recurrent joint bleeding progresses to hemophilic arthropathy. Repeated bleeding leads to iron deposition and chronic inflammation, resulting in gradual deterioration of joint function through joint capsule thickening and muscle atrophy. These changes commonly occur in the elbows, knees, and ankles, causing significant difficulties in walking and daily activities.

Much of this damage progresses through so-called silent bleeding, which patients may not immediately recognize, delaying intervention until functional impairment becomes evident.

KBR: With the shift in the treatment paradigm towards “prophylactic therapy,” there might have been significant changes in clinical practice.

Professor Hahn Seung-min (HSM): The most decisive change is the significant reduction in bleeding episodes. In the past, the goal was merely to maintain clotting factor levels above 1 percent. However, recent studies consistently show that higher levels yield greater preventive effects. Yet maintaining high concentrations requires more frequent and higher-dose medication administration, which poses a practical burden.

KBR: Despite the importance of prophylactic therapy, what are the practical difficulties hindering its implementation?

HSM: Countries leading recent hemophilia research and treatment are proposing that higher clotting factor levels correlate with greater bleeding prevention. However, maintaining consistently high clotting factor concentrations requires either more frequent administration or higher doses. As a result, even patients on prophylactic therapy continue to face residual bleeding risk, along with the burden of ongoing treatment.

AWK: The first barrier is awareness. Even severe patients often fail to recognize the necessity of prophylactic therapy if they experience no visible bleeding. However, repeated unnoticed bleeding leads to cumulative tissue damage. The second barrier is the burden of medication. The requirement for intravenous injections two to three times per week causes physical and emotional distress for both patients and caregivers.

Professor Han Jung-woo (HJW): For pediatric patients, intravenous injections themselves are complicated, and caregivers experience extreme stress when injections are not successful on the first attempt. For this reason, even though three weekly doses are necessary, clinicians often face practical dilemmas when trying to maintain optimal dosing frequency.

KBR: Recently, long-acting coagulation factor formulations, which maintain near-normal coagulation factor levels with just one injection per week, have been introduced. What changes are expected in the clinical setting?

HSM: If we can reduce injections from 12 times a month to just four, it will dramatically transform the patient’s life. Particularly with the latest agent, Altuviiio (efanexoctocog alfa), a single weekly dose can maintain coagulation factor activity above 15 percent, allowing patients to continue prophylaxis much more easily without constant anxiety about bleeding.

KBR: What is noteworthy in Altuviiio’s clinical data?

HSM: The results from the XTEND-1 (adults/adolescents) and XTEND-Kids (pediatric) clinical trials showed that the median annual spontaneous bleeding rate and joint bleeding rate were both “0.0” with once-weekly prophylaxis in the study populations. It is highly encouraging that a stable “zero bleeding” effect was observed across age groups.

KBR: With more treatment options available, healthcare providers’ selection criteria will likely change.

HSM: Currently in Korea, treatment selection is often constrained by the scope of national health insurance coverage, limiting the options available to patients and healthcare providers. For hemophilia A, treatment options are broadly categorized into three types: standard half-life (SHL) products, extended half-life (EHL) products, and antifactor VIII antibody therapies.

For hemophilia B, standard half-life (SHL) or extended half-life (EHL) products are also the primary treatment options. In this environment, treatment choices are often determined by the patient’s preference for prophylaxis. However, as new agents are introduced, it is crucial to select the most appropriate treatment by comprehensively considering the patient’s clinical profile, lifestyle, age, and long-term treatment sustainability.

AWK: We must now design personalized treatment plans by comprehensively considering the patient’s age, individual bleeding patterns, lifestyle, and long-term medication sustainability. The ultimate goal is to ensure patients can engage in daily activities like exercise and social interactions without anxiety about bleeding.

KBR: Are there any shortcomings in the current domestic hemophilia reimbursement system or framework?

HSM: The system strictly limits drug dosage and frequency, making it difficult to prescribe flexibly based on the patient’s condition. The process of changing or adjusting treatments based on changes in the patient’s age or health status needs to be smoother.

AWK: Even when new drugs are introduced, domestic reimbursement criteria sometimes fail to reflect overseas clinical evidence adequately. We must bridge the gap between clinical practice and the system so that domestic patients can fully benefit from treatment efficacy proven in international studies.

KBR: Severance Hospital emphasizes a multidisciplinary care system (K-HTC) for the treatment of hemophilia. What is the background for this?

HJW: Hemophilia isn’t just about administering clotting factors. Collaboration across departments such as orthopedics, dentistry, and physical medicine and rehabilitation is essential. As patients’ lifespans increase, managing chronic conditions and cardiovascular health has also become crucial. Building on our experience establishing Korea’s first hemophilia clinic in 1987, Severance Hospital aims to establish the role of the “Korean Hemophilia Treatment Center (K-HTC),” centered around university hospitals.

KBR: What would you like to emphasize to patients, caregivers, and primary care providers?

AWK: I would like to encourage patients to maintain continuous interest in new treatments and to communicate thoroughly with medical professionals to find the treatment method that best suits them. Furthermore, if structured collaboration between tertiary hospitals and primary care providers is established, patients can be managed more safely in daily life.

HSM: Hemophilia patients often have low physical activity levels, increasing their risk of chronic diseases and osteoporosis. If a treatment environment with minimal bleeding is established, increased activity could significantly improve overall health.

HJW: While treatments are advancing, unmet needs still exist. We will continue researching and evaluating how to appropriately combine various treatment options rather than relying on a single approach. Our goal is to support patients so they can live without lifelong fear of bleeding.