Table 3.
Evaluation of thrombotic events as of October 20, 2020, in the fitusiran clinical development program.a,b
| Patient characteristics |
Medical history/comments | AT category | Thrombotic eventc | |
|---|---|---|---|---|
| Age range (y) | Hemophilia subtype and inhibitor status | |||
| 30-40 | Person with hemophilia A without inhibitor | Deep-vein thrombosis (not identified at enrollment; a study exclusion criterion), diabetes, obesity, HCV and tobacco use | <10% | Cerebrovascular accident |
| >60 | Person with hemophilia A without inhibitor | Well-controlled HIV, HCV, and prostate cancer status-post radical prostatectomy with recent prostate-specific antigen within normal limits | <10% | Cerebral infarct |
| 20-30 | Person with hemophilia A with inhibitor | Suspected thrombosis involving a spinal injury | <10% | Spinal vascular disorder |
| 20-30 | Person with hemophilia B with inhibitor | Concomitant use of BPA (rFVIIa) in excess of the current bleed management guidelines in fitusiran clinical studies | 10%-20% | Atrial thrombosis |
| 20-30 | Person with hemophilia A without inhibitor | Concomitant use of factor concentrate in excess of the current bleed management guidelines. Event was initially misdiagnosed and treated as a subarachnoid hemorrhage and resulted in a fatal outcome | 10%-20% | Cerebral venous sinus thrombosis |
AT, antithrombin; BPA, bypassing agent; HCV, hepatitis C.
Table adapted with permission from Negrier et al. [61].
As of November 5, 2020, 259 participants have received at least 1 dose of fitusiran in the clinical development program, with an estimated total of 293 patient-years of exposure, excluding the data in phase I and pediatric studies.
For all adult and adolescent patients exposed to at least 1 dose of fitusiran, the total patient-years for each of the 3 AT categories was calculated: <10%, 10% to 20%, and >20%. The patients with vascular thrombotic events were then included in the AT category representative of their level for the greatest amount of time during fitusiran exposure and an incident rate per 100 patient-years was derived.
Adverse event data as of October 20, 2020.