TY - JOUR
T1 - Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia a or B without Inhibitors (ATLAS-A/B)
T2 - Late-Breaking Abstracts
AU - Srivastava, Alok
AU - Rangarajan, Savita
AU - Kavakli, Kaan
AU - Klamroth, Robert
AU - Kenet, Gili
AU - Khoo, Liane
AU - You, Chur-Woo
AU - Xu, Weiqun
AU - Malan, Niel
AU - Frenzel, Laurent
AU - Bagot, Catherine N.
AU - Stasyshyn, Oleksandra
AU - Chang, Chia-Yau
AU - Poloskey, Stacey
AU - Andersson, Shauna
AU - Qiu, Zhiying
AU - Mei, Baisong
AU - Pipe, Steven W.
PY - 2021
Y1 - 2021
N2 - Background Hemophilia is a rare bleeding disorder characterized by deficiency of FVIII or FIX resulting in ineffective clot formation due to impaired thrombin generation. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic agent which targets antithrombin to enhance thrombin generation potential and rebalance hemostasis in people with hemophilia (PwH), irrespective of inhibitor status. Here, we present results from a Phase 3 study of the efficacy and safety of fitusiran prophylaxis compared with on-demand (OD) treatment with factor concentrates in PwH A or B without inhibitors (ATLAS-A/B; NCT03417245). Methods This Phase 3, multicenter, multinational, randomized, open-label study evaluated the efficacy and safety of fitusiran in males aged ≥12 years with severe hemophilia A or B without inhibitors, previously treated OD. Eligible participants (pts) were randomized 2:1 to receive either once-monthly 80 mg SC fitusiran prophylaxis (fitusiran arm) or OD factor concentrates for treatment of bleeding episodes (OD arm) for a treatment period of 9 months. The primary endpoint was annualized bleeding rate (ABR) in the efficacy period (Day 29 post-first fitusiran dose up to Day 246). Secondary endpoints included annualized spontaneous bleeding rate (AsBR) and annualized joint bleeding rate (AJBR) in the efficacy period and health-related quality of life (HRQoL) in the treatment period, measured by Haem-A-QoL. Safety and tolerability were assessed throughout the study. Results Overall, 120 pts were randomized (fitusiran arm n=80; OD arm n=40); 79 pts (98.8%) in the fitusiran arm and 37 pts (92.5%) in the OD arm completed the study. A total of 93 pts had hemophilia A (fitusiran arm n=62, OD arm n=31) and 27 pts had hemophilia B (fitusiran arm n=18, OD arm n=9). Baseline demographics and characteristics were similar in both arms. Median observed ABR was 0.0 (IQR, 0.0 to 3.4) in the fitusiran arm and 21.8 (IQR, 8.4 to 41.0) in the OD arm; 40 pts (50.6%) in the fitusiran arm experienced no bleeds that required treatment with OD factor concentrates. A significant reduction in estimated ABR was achieved in the fitusiran arm vs the OD arm (89.9% reduction [95% CI, 84.1% to 93.6%], p
AB - Background Hemophilia is a rare bleeding disorder characterized by deficiency of FVIII or FIX resulting in ineffective clot formation due to impaired thrombin generation. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic agent which targets antithrombin to enhance thrombin generation potential and rebalance hemostasis in people with hemophilia (PwH), irrespective of inhibitor status. Here, we present results from a Phase 3 study of the efficacy and safety of fitusiran prophylaxis compared with on-demand (OD) treatment with factor concentrates in PwH A or B without inhibitors (ATLAS-A/B; NCT03417245). Methods This Phase 3, multicenter, multinational, randomized, open-label study evaluated the efficacy and safety of fitusiran in males aged ≥12 years with severe hemophilia A or B without inhibitors, previously treated OD. Eligible participants (pts) were randomized 2:1 to receive either once-monthly 80 mg SC fitusiran prophylaxis (fitusiran arm) or OD factor concentrates for treatment of bleeding episodes (OD arm) for a treatment period of 9 months. The primary endpoint was annualized bleeding rate (ABR) in the efficacy period (Day 29 post-first fitusiran dose up to Day 246). Secondary endpoints included annualized spontaneous bleeding rate (AsBR) and annualized joint bleeding rate (AJBR) in the efficacy period and health-related quality of life (HRQoL) in the treatment period, measured by Haem-A-QoL. Safety and tolerability were assessed throughout the study. Results Overall, 120 pts were randomized (fitusiran arm n=80; OD arm n=40); 79 pts (98.8%) in the fitusiran arm and 37 pts (92.5%) in the OD arm completed the study. A total of 93 pts had hemophilia A (fitusiran arm n=62, OD arm n=31) and 27 pts had hemophilia B (fitusiran arm n=18, OD arm n=9). Baseline demographics and characteristics were similar in both arms. Median observed ABR was 0.0 (IQR, 0.0 to 3.4) in the fitusiran arm and 21.8 (IQR, 8.4 to 41.0) in the OD arm; 40 pts (50.6%) in the fitusiran arm experienced no bleeds that required treatment with OD factor concentrates. A significant reduction in estimated ABR was achieved in the fitusiran arm vs the OD arm (89.9% reduction [95% CI, 84.1% to 93.6%], p
U2 - 10.1182/blood-2021-155018
DO - 10.1182/blood-2021-155018
M3 - Article
SN - 0006-4971
VL - 138
SP - LBA-3
JO - Blood
JF - Blood
ER -