Bleeding events in the fitusiran and BPA/CFC prophylaxis period (EAS 1)
Event . | Inhibitor . | Noninhibitor . | Overall . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| BPA PPX (n = 19) . | Fitusiran 80 mg PPX (n = 19) . | P value∗ . | CFC PPX (n = 46) . | Fitusiran 80 mg PPX (n = 46) . | P value∗ . | BPA/CFC PPX (n = 65) . | Fitusiran 80 mg PPX (n = 65) . | P value∗ . | |
| Any treated bleeding event | |||||||||
| Estimated ABR (95% CI) | 11.4 (7.4-17.7) | 2.3 (0.8-6.6) | 5.9 (4.0-8.7) | 3.2 (1.7-5.8) | 7.5 (5.5-10.1) | 2.9 (1.7-4.9) | |||
| ABR reduction, % | 79.7 | .0021 | 46.4 | .0598 | 61.1 | .0008 | |||
| Median ABR (IQR) | 6.5 (2.2; 19.6) | 0.0 (0.0; 0.0) | 4.4 (2.2; 8.7) | 0.0 (0.0; 2.7) | 4.4 (2.2; 10.9) | 0.0 (0.0; 2.3) | |||
| Participants with 0 treated bleeds, n (%) | 1 (5.3) | 15 (78.9) | 10 (21.7) | 26 (56.5) | 11 (16.9) | 41 (63.1) | |||
| Treated spontaneous bleeds | |||||||||
| Estimated AsBR (95% CI) | 7.2 (4.4-11.8) | 1.9 (0.7-5.7) | 4.1 (2.4-7.0) | 2.4 (1.1-5.1) | 5.0 (3.4-7.3) | 2.2 (1.2-4.2) | |||
| AsBR reduction, % | 73.2 | .0100 | 42.3 | .1842 | 55.6 | .0129 | |||
| Median AsBR (IQR) | 4.4 (2.2-15.2) | 0.0 (0.0-0.0) | 2.2 (0.0; 4.4) | 0.0 (0.0-2.3) | 2.2 (0.0-6.5) | 0.0 (0.0-2.3) | |||
| Participants with 0 spontaneous treated bleeds, n (%) | 3 (15.8) | 15 (78.9) | 20 (43.5) | 31 (67.4) | 23 (35.4) | 46 (70.8) | |||
| Treated joint bleeds | |||||||||
| Estimated AjBR (95% CI) | 7.9 (4.7, 13.0) | 2.1 (0.7, 5.8) | 4.2 (2.5, 7.1) | 2.8 (1.4, 5.5) | 5.3 (3.6, 7.7) | 2.6 (1.4, 4.6) | |||
| AjBR reduction, % | 73.6 | .0207 | 34.4 | .2681 | 51.5 | .0242 | |||
| Median AjBR (IQR) | 4.4 (0.0-15.2) | 0.0 (0.0-0.0) | 2.2 (0.0-4.4) | 0.0 (0.0-2.3) | 2.2 (0.0-6.5) | 0.0 (0.0-2.3) | |||
| Participants with 0 joint treated bleeds, n (%) | 5 (26.3) | 15 (78.9) | 17 (37.0) | 29 (63.0) | 22 (33.8) | 44 (67.7) | |||
Event . | Inhibitor . | Noninhibitor . | Overall . | ||||||
|---|---|---|---|---|---|---|---|---|---|
| BPA PPX (n = 19) . | Fitusiran 80 mg PPX (n = 19) . | P value∗ . | CFC PPX (n = 46) . | Fitusiran 80 mg PPX (n = 46) . | P value∗ . | BPA/CFC PPX (n = 65) . | Fitusiran 80 mg PPX (n = 65) . | P value∗ . | |
| Any treated bleeding event | |||||||||
| Estimated ABR (95% CI) | 11.4 (7.4-17.7) | 2.3 (0.8-6.6) | 5.9 (4.0-8.7) | 3.2 (1.7-5.8) | 7.5 (5.5-10.1) | 2.9 (1.7-4.9) | |||
| ABR reduction, % | 79.7 | .0021 | 46.4 | .0598 | 61.1 | .0008 | |||
| Median ABR (IQR) | 6.5 (2.2; 19.6) | 0.0 (0.0; 0.0) | 4.4 (2.2; 8.7) | 0.0 (0.0; 2.7) | 4.4 (2.2; 10.9) | 0.0 (0.0; 2.3) | |||
| Participants with 0 treated bleeds, n (%) | 1 (5.3) | 15 (78.9) | 10 (21.7) | 26 (56.5) | 11 (16.9) | 41 (63.1) | |||
| Treated spontaneous bleeds | |||||||||
| Estimated AsBR (95% CI) | 7.2 (4.4-11.8) | 1.9 (0.7-5.7) | 4.1 (2.4-7.0) | 2.4 (1.1-5.1) | 5.0 (3.4-7.3) | 2.2 (1.2-4.2) | |||
| AsBR reduction, % | 73.2 | .0100 | 42.3 | .1842 | 55.6 | .0129 | |||
| Median AsBR (IQR) | 4.4 (2.2-15.2) | 0.0 (0.0-0.0) | 2.2 (0.0; 4.4) | 0.0 (0.0-2.3) | 2.2 (0.0-6.5) | 0.0 (0.0-2.3) | |||
| Participants with 0 spontaneous treated bleeds, n (%) | 3 (15.8) | 15 (78.9) | 20 (43.5) | 31 (67.4) | 23 (35.4) | 46 (70.8) | |||
| Treated joint bleeds | |||||||||
| Estimated AjBR (95% CI) | 7.9 (4.7, 13.0) | 2.1 (0.7, 5.8) | 4.2 (2.5, 7.1) | 2.8 (1.4, 5.5) | 5.3 (3.6, 7.7) | 2.6 (1.4, 4.6) | |||
| AjBR reduction, % | 73.6 | .0207 | 34.4 | .2681 | 51.5 | .0242 | |||
| Median AjBR (IQR) | 4.4 (0.0-15.2) | 0.0 (0.0-0.0) | 2.2 (0.0-4.4) | 0.0 (0.0-2.3) | 2.2 (0.0-6.5) | 0.0 (0.0-2.3) | |||
| Participants with 0 joint treated bleeds, n (%) | 5 (26.3) | 15 (78.9) | 17 (37.0) | 29 (63.0) | 22 (33.8) | 44 (67.7) | |||
Fitusiran efficacy period (fitusiran prophylaxis) was defined as starting on day 29 after the first dose of fitusiran up to day 190 or the last day of bleeding follow-up, whichever was the earliest. The BPA/CFC prophylaxis period was defined as starting on day –168 to day –1 or the last day of bleeding follow-up, whichever was the earliest. EAS 1 includes all participants who received BPA/CFC prophylaxis and at least 1 dose of 80 mg fitusiran before dose resumption (after the sponsor initiated pause in dosing).
The analysis is based on an on-treatment strategy, which included all treated bleeding events in the fitusiran efficacy period and the BPA/CFC prophylaxis period and excluded any bleeding events in the period of intercurrent events.
PPX, prophylaxis.
P value from a negative binomial regression model with study period (fitusiran efficacy period or BPA/CFC prophylaxis period) as a fixed effect and a robust sandwich covariance matrix constructed to account for the within subject dependence, the logarithm of the duration (in years) that each participant spends in each study period matching the bleeding episode data being analyzed as an offset variable (P value vs null hypothesis of ratio = 1).