Clinical outcomes up to 4 years of once-weekly efanesoctocog alfa prophylaxis in previously treated adults, adolescents, and children with severe hemophilia A: Interim analysis of the Phase 3 XTEND-ed long-term extension study
Notice bibliographique
Résumé
Abstract Introduction Efanesoctocog alfa is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to decouple recombinant FVIII from endogenous von Willebrand factor. In the Phase 3 XTEND-1 (NCT04161495) and XTEND-Kids (NCT04759131) studies, once-weekly efanesoctocog alfa exhibited effective bleed protection, was well tolerated, providing FVIII activity within the normal to near-normal (>40%) range for 4 and 3 days, respectively, at steady state. We present the third interim analysis of the XTEND-ed (NCT04644575) long-term extension study examining the safety and efficacy of efanesoctocog alfa prophylaxis in patients with severe hemophilia A. Methods Participants who completed XTEND-1 (≥12 years) and XTEND-Kids (<12 years), could continue once-weekly 50 IU/kg efanesoctocog alfa prophylaxis in the ongoing, multicenter, open-label, long-term XTEND-ed study. The primary endpoint was the incidence of FVIII inhibitor development and secondary endpoints included annualized bleed rates (ABRs), efficacy for bleed treatment, and safety. Data cut: February 21, 2025. Results Among adults and adolescents, 146 participants rolled over from XTEND-1 to XTEND-ed baseline with a median (range) age of 37.0 (13.0–74.0) years. The median (range) treatment duration in XTEND-ed was 166.0 (14.1–192.7) weeks, comprising a median (range) of 167.0 (14.0–200.0) exposure days (EDs). The median (range) cumulative treatment duration from XTEND-1 baseline until XTEND-ed data cut was 212.2 (46.3–244.8) weeks, comprising a median (range) of 216.5 (47.0–254.0) EDs. No FVIII inhibitor development was observed. During XTEND-ed, the mean (SD) ABR for Day 1–Month 12 (n=146) was 0.70 (1.31), Months 12–24 (n=141) was 0.62 (1.23) and Months 24–36 (n=132) was 0.45 (1.24), with 96/146 (65.8%), 96/141 (68.1%), and 103/132 (78.0%) participants with zero bleeds, respectively. The mean (95% CI) model-based ABR for the efficacy period was 0.60 (0.47; 0.76) for overall treated bleeds, and 0.20 (0.15; 0.28) and 0.29 (0.22; 0.39) for spontaneous and traumatic bleeds, respectively. Of 252 treated bleeding episodes, 94.0% (237) were resolved with 1 efanesoctocog alfa injection; participants rated the response excellent/good for 87.8% (173/197) bleeds. The median (range) weekly efanesoctocog alfa consumption was 51.6 (39.4–58.9) IU/kg. In total, 126 participants (86.3%) experienced ≥1 treatment-emergent adverse event (TEAE), most commonly COVID-19 (26.7%), arthralgia (17.1%), influenza (15.1%), and nasopharyngitis (15.1%). Two participants had ≥1 treatment-related TEAE (facial paralysis and reduced FVIII levels); no treatment-related serious TEAEs were reported. TEAEs unrelated to study drug led to the death of 2 participants and treatment discontinuation in 3 participants. Among children, 71 participants (<6 years, n=35; 6–<12 years, n=36) rolled over from XTEND-Kids to XTEND-ed, with the median (range) treatment duration of 116.7 (36.3–152.6) weeks, comprising a median (range) of 116.0 (11.0–153.0) EDs. The median (range) cumulative treatment duration from XTEND-Kids baseline until XTEND-ed data cut was 169.8 (88.2–204.7) weeks, with a median (range) of 171.0 (65.0–207.0) EDs. No FVIII inhibitors were observed. During XTEND-ed, the mean (SD) ABR evaluated for Day 1–Month 12 (n=71) was 0.68 (1.13) and Months 12–24 (n=62) was 0.49 (0.82), with 46/71 (64.8%) and 41/62 (66.1%) participants with zero bleeds, respectively. The mean (95% CI) model-based ABR was 0.64 (0.48; 0.85) for overall treated bleeds, and 0.08 (0.04; 0.15) and 0.44 (0.31; 0.62) for spontaneous and traumatic bleeds, respectively. Of 89 treated bleeding episodes, 91.0% (81) were resolved with 1 efanesoctocog alfa injection; participants rated the response excellent/good for 94.1% (64/68) bleeds. The median (range) weekly efanesoctocog alfa consumption was 54.0 (46.2–73.1) IU/kg. Overall, 60 (84.5%) participants experienced ≥1 TEAE; most commonly pyrexia (18.3%), upper respiratory tract infection (16.9%), arthralgia (15.5%), and cough (15.5%). Two participants had ≥1 treatment-related TEAE (asthma and post infusion pain and headache); no treatment-related serious TEAEs or treatment discontinuations were reported. Conclusion Results from up to 4 years of the XTEND-ed study demonstrate that once-weekly efanesoctocog alfa continues to be well tolerated, providing highly effective bleed protection with no inhibitor development in adults, adolescents, and children with severe hemophilia A.
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 | 0,004 |
| 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 | 0,001 | 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 ».