Clinical Outcomes over 3 Years of Once-Weekly Efanesoctocog Alfa Treatment in Adults and Adolescents with Severe Hemophilia A: Second Interim Analysis from the Phase 3 XTEND-ed Long-Term Extension Study
Bibliographic record
Abstract
Introduction Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to decouple FVIII from endogenous von Willebrand factor. In the Phase 3 XTEND-1 study (NCT04161495), once-weekly efanesoctocog alfa demonstrated superior bleed protection over prior FVIII prophylaxis, was well tolerated, and provided FVIII activity within the normal to near-normal (>40%) range for most of the week. Here we present data from the second interim analysis of the long-term safety and efficacy of efanesoctocog alfa in adults and adolescents with severe hemophilia A in the XTEND-ed study (NCT04644575). Methods Previously treated patients (≥12 years) who completed XTEND-1 could continue efanesoctocog alfa (50 IU/kg, once-weekly) prophylaxis in the multicenter, open-label, long-term XTEND-ed study (Arm A). The primary endpoint is incidence of FVIII inhibitor development (determined by the Nijmegen modified Bethesda assay). Secondary endpoints include annualized bleed rates (ABRs), efficacy for bleed treatment, patient-reported quality of life (QoL) outcomes, and safety. XTEND-ed was approved by local ethics committees; participants provided informed consent. Data cut: February 22, 2024. Results A total of 146 participants (including 1 female) rolled over from XTEND-1 to Arm A of XTEND-ed (age: 12-17 years, n=21; 18-64 years, n=120; ≥65 years, n=5). The median (range) treatment duration in XTEND-ed was 120.6 (14.1-140.6) weeks comprising a median (range) of 121.5 (14-147) exposure days (EDs). The median (range) cumulative treatment duration from XTEND-1 baseline was 170.5 (46.3-192.6) weeks with median (range) 171.5 (47-201) EDs. FVIII inhibitors were not detected. During XTEND-ed, the mean (standard deviation [SD]) ABRs for Day 1-Month 6 (n=146) was 0.63 (1.6), Months 6-12 (n=144) was 0.77 (1.54), Months 12-18 (n=139) was 0.65 (1.67), and Months 18-24 (n=138) was 0.58 (1.64). The number of participants with zero bleeds for Day 1-Month 6 was 116 of 146 (79.5%), Months 6-12 was 107 of 144 (74.3%), Months 12-18 was 109 of 139 (78.4%), and Months 18-24 was 111 of 138 (80.4%). The mean (95% confidence interval) model-based ABR for the whole efficacy period was 0.64 (0.50; 0.82). Of 205 treated bleeding episodes, 194 (94.6%) resolved with 1 injection of efanesoctocog alfa; participants rated the response as excellent/good for 139/160 (86.9%) bleeds. The median (range) total weekly efanesoctocog alfa consumption was 51.6 (39.4-61.0) IU/kg. The Haem-A-QoL total score and physical health score, analyzed in 102 participants (age: ≥17 years), showed an improvement with mean (SD) change from baseline (XTEND-1) to XTEND-ed Month 24 of -5.8 (13.35) and -7.5 (20.05), respectively. Overall, 117 (80.1%) participants experienced ≥1 treatment-emergent adverse event (TEAE), the most commonly reported being COVID-19 (25.3%), arthralgia (15.1%), and nasopharyngitis (12.3%). Twenty-two participants (15.1%) experienced ≥1 serious TEAE including 2 participants with thromboembolic events: one was a deep vein thrombosis following corrective surgery for a femur fracture (in the setting of treatment with another FVIII product), the other was a cerebral infarction in a participant with pre-existing atrial fibrillation and other risk factors; neither event was related to efanesoctocog alfa treatment. Conclusion Long-term results in adults and adolescents in XTEND-ed shows that once-weekly efanesoctocog alfa continues to provide high efficacy and is well tolerated. No inhibitors were detected and ABRs remained low, with continued improvement observed for overall QoL.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".