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
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».