Summary of AEs (SAS 1)
| Event, n (%) . | BPA/CFC prophylaxis (n = 65) . | Fitusiran 80 mg prophylaxis (n = 67∗) . |
|---|---|---|
| Participants with any AE | 22 (33.8) | 48 (71.6) |
| Most common AEs in fitusiran group (in >5% of participants) | ||
| ALT increased | 1 (1.5) | 18 (26.9) |
| Nasopharyngitis | 1 (1.5) | 8 (11.9) |
| Upper respiratory tract infection | 4 (6.2) | 6 (9.0) |
| Arthralgia | 4 (6.2) | 5 (7.5) |
| Cholelithiasis | 0 | 5 (7.5) |
| Fibrin D-dimer increased | 0 | 5 (7.5) |
| Injection site pain | 0 | 5 (7.5) |
| AST increased | 1 (1.5) | 4 (6.0) |
| Cholecystitis | 0 | 4 (6.0) |
| Cough | 0 | 4 (6.0) |
| Participants with any SAE | 5 (7.7) | 9 (13.4) |
| SAEs assessed as related to fitusiran† | N/A | 3 (4.5) |
| Cerebrovascular accident | N/A | 1 (1.5) |
| Acute pancreatitis | N/A | 1 (1.5) |
| Cholelithiasis | N/A | 1 (1.5) |
| Most common SAEs‡ | ||
| Hemophilic arthropathy§ | 2 (3.1) | 2 (3.0) |
| Participants with any AESI | 2 (3.1) | 22 (32.8) |
| Any suspected or confirmed thromboembolic events‖ | 0 | 2 (3.0) |
| Any ALT or AST elevations >3× ULN¶ | 2 (3.1) | 17 (25.4) |
| Cholecystitis# | 0 | 5 (7.5) |
| Cholelithiasis | 0 | 5 (7.5) |
| Participants with any AE leading to fitusiran discontinuation∗∗ | N/A | 2 (3.0) |
| Participants with any AE leading to study withdrawal∗∗ | 0 | 2 (3.0) |
| Participants with any AE leading to death | 0 | 0 |
| Event, n (%) . | BPA/CFC prophylaxis (n = 65) . | Fitusiran 80 mg prophylaxis (n = 67∗) . |
|---|---|---|
| Participants with any AE | 22 (33.8) | 48 (71.6) |
| Most common AEs in fitusiran group (in >5% of participants) | ||
| ALT increased | 1 (1.5) | 18 (26.9) |
| Nasopharyngitis | 1 (1.5) | 8 (11.9) |
| Upper respiratory tract infection | 4 (6.2) | 6 (9.0) |
| Arthralgia | 4 (6.2) | 5 (7.5) |
| Cholelithiasis | 0 | 5 (7.5) |
| Fibrin D-dimer increased | 0 | 5 (7.5) |
| Injection site pain | 0 | 5 (7.5) |
| AST increased | 1 (1.5) | 4 (6.0) |
| Cholecystitis | 0 | 4 (6.0) |
| Cough | 0 | 4 (6.0) |
| Participants with any SAE | 5 (7.7) | 9 (13.4) |
| SAEs assessed as related to fitusiran† | N/A | 3 (4.5) |
| Cerebrovascular accident | N/A | 1 (1.5) |
| Acute pancreatitis | N/A | 1 (1.5) |
| Cholelithiasis | N/A | 1 (1.5) |
| Most common SAEs‡ | ||
| Hemophilic arthropathy§ | 2 (3.1) | 2 (3.0) |
| Participants with any AESI | 2 (3.1) | 22 (32.8) |
| Any suspected or confirmed thromboembolic events‖ | 0 | 2 (3.0) |
| Any ALT or AST elevations >3× ULN¶ | 2 (3.1) | 17 (25.4) |
| Cholecystitis# | 0 | 5 (7.5) |
| Cholelithiasis | 0 | 5 (7.5) |
| Participants with any AE leading to fitusiran discontinuation∗∗ | N/A | 2 (3.0) |
| Participants with any AE leading to study withdrawal∗∗ | 0 | 2 (3.0) |
| Participants with any AE leading to death | 0 | 0 |
N/A, not applicable.
Includes all participants who enrolled and then received at least 1 dose of fitusiran before dose resumption (after the sponsor initiated pause in dosing).
The participant with cerebrovascular accident recovered from the event with sequelae 28 days after the onset. This event resulted in fitusiran discontinuation and study withdrawal. Acute pancreatitis and cholelithiasis were assessed as serious because the need for hospitalization; both of these events were resolved by the end of the study.
In the BPA/CFC prophylaxis period, additional SAEs included gastroenteritis, hemarthrosis, and muscle hemorrhage (1 [1.5%] participant each). In the fitusiran prophylaxis period, additional SAEs included vascular device infection, biliary neoplasm, cerebrovascular accident, asthma late onset, acute pancreatitis, cholelithiasis, Stevens-Johnson syndrome (occurred 62 days after the last dose of fitusiran prophylaxis; the event was due to an allergic reaction to concomitant medications and was assessed by the investigator as not related to fitusiran prophylaxis), C-reactive protein increased, fall, femur fracture, and central venous catheter removal (1 [1.5%] participant each).
Reported as worsening of hemophilic arthropathy. Both participants with events of worsening of hemophilic arthropathy during fitusiran prophylaxis had the history of hemophilic arthropathy ongoing before the study entry. Because of traumatic joint bleeds, these events occurred, and participants recovered from these events within 2-3 days of onset. None of the events were assessed by the investigator as related to fitusiran prophylaxis.
Includes AEs of cerebrovascular accident and thrombosis (suspected thrombosis on papilla of left eye). The participant with cerebrovascular accident had a history of right lower extremity deep vein thrombosis not known by the investigator at the time of enrollment (exclusion criterion).
Laboratory abnormalities consistent with Hy’s law were identified in 1 of these participants at the end of study visit. Additional doses of fitusiran were not administered and all abnormalities resolved.
Includes one AE of chronic cholecystitis.
Includes AEs of cerebrovascular accident and abdominal discomfort.