Clinical Research Directory

Efanesoctocog Prophylaxis Or The Optimization Of Treatment: Real-World Experience Of Taylorizing Clotting Therapy In Hemophilia A

Prophylactic management of severe Hemophilia A (HA) without inhibitors has historically relied on frequent intravenous infusions of standard or EHL FVIII concentrates or on subcutaneous emicizumab administered weekly to monthly intervals , yet both approaches maintain a notable treatment burden and variable factor utilization. Efanesoctocog alfa (ALTUVOCT®, Swedish Orphan Biovitrum SOBI) was engineered as a fusion of FVIII, von Willebrand factor (VWF) binding domains, and XTEN polypeptides to decouple FVIII from endogenous VWF and extend its circulatory half-life beyond that of existing EHL concentrates. In the pivotal XTEND-1 trial (NCT04161495) of 159 patients aged ≥ 12 years, once-weekly prophylaxis (50 IU/kg) yielded a mean ABR of 0.70 episodes per patient-year versus approximately 3.0 episodes on prior regimens. The study ended with superior bleeding protection, with FVIII activity above 40 IU/dL for the majority of each week and of 15 IU/dL at day 7. In children under 12, XTEND-Kids phase 3 data (n = 74) demonstrated comparable bleeding control; the average ABR for patients per year was 0.70. The XTEND-ed long-term extension (3-year data) assessed maintaining low ABRs, stable FVIII levels, and consistent tolerability. Efanesoctocog alfa was also well-tolerated in all trials, with adverse events similar to those of other FVIII products and no inhibitor development reported as a result of treatment. The analysis of pharmacokinetics indicated an extended half-life that supports once-weekly dosing and maintains FVIII activity in the normal to near-normal range (\> 40 IU/dL) for the majority of each dosing interval. While regulatory and health-technology assessments recognize its favorable pharmacokinetics and hemostatic efficacy, they underscore the non-randomized, intra-patient design of these studies, the paucity of robust head-to-head comparisons with standard FVIII or emicizumab, and the absence of real-world QoL and consumption data. Despite the promising results, critical questions remain unanswered in routine clinical practice: efanesoctocog alfa is designed for once-weekly dosing but how does switching to efanesoctocog alfa alter real-world FVIII consumption, what clinical or psychosocial factors drive clinicians and patients to transition, and how do patients perceive efficacy, convenience, and treatment burden post-switch? This study is designed to bridge this knowledge gap by quantifying pre- and post-switch FVIII utilization, systematically capturing switch-motivations through patient interviews, and applying validated patient-reported outcome measures to assess satisfaction and QoL impacts. Addressing these dimensions will not only inform personalized prophylaxis regimens and clarify resource utilization but also enrich pharmaco-economic models and guide future therapeutic innovations in HA management. Individual profit - The switched patient must benefit from a lower injection frequency for the same clinical outcome (change of prescription); this could also favorably impact his quality of life. The possibility of changing the replacement therapy with FVIII or emicizumab to efanesoctocog alfa will be proposed to the patient during a routine consultation. The Patient-Reported Outcome Measures (PROMs) will make it possible to properly appraise the patient's view. QoL questionnaires (PERQOLATEUR), Hemophilia Functional Ability Scoring Tool questionnaires (Hemo-FAST©) and treatment evaluation questionnaires will be presented (See Appendice 8), particularly during the shared decision-making consultation on the switch and the following routine consultation. Group profit - This study will allow a better understanding of the use of health resources (quantification of FVIII consumption before and after switching to efanesoctocog alfa), to better understand the motivations of a person with HA to change treatment, and to evaluate in a real situation the impact on the patient's QoL of a new substitutive treatment. The research has no risks and constraints because only questionnaires (part of routine care or without health data) are distributed to patients.

Real-World Joint Outcomes After Selective Transition to Low-Dose Emicizumab in Pediatric Hemophilia A

Recent studies have shown that pharmacokinetic (PK)-guided extended half-life (EHL) factor VIII can improve joint health in patients with hemophilia A. However, some patients experience suboptimal joint outcomes despite optimized PK-guided therapy. Low-dose emicizumab has emerged as a potential option for improving bleeding control and joint health in patients who do not respond adequately to PK-guided EHL factor VIII. The objectives of the study is to compare clinical bleeding outcomes, joint health, cartilage biomarkers, and musculoskeletal ultrasound findings (HEAD-US) in hemophilia A patients in Thailand during PK-guided EHL factor VIII therapy and after switching to low-dose emicizumab. Eighteen patients with hemophilia A from King Chulalongkorn Memorial Hospital, Thailand, aged 8-28 years, who were receiving PK-guided EHL factor VIII were enrolled. Patients with a Hemophilia Joint Health Score (HJHS) ≥ 12 were switched to low-dose emicizumab. A loading dose of 2 mcg/kg was administered, followed by dosing every 2 weeks during the first month and every 4 weeks thereafter. Clinical bleeding, annual bleeding rate (ABR), annual joint bleeding rate (AJBR), HJHS, cartilage biomarkers, and musculoskeletal ultrasound findings (HEAD-US) were evaluated every 4 months for up to 8 months after switching.