Figure 5.

Fitusiran revised dose and dose regimen, targeting an antithrombin range from 15% to 35% [62]. The revised dose and dose regimen was introduced as of December 2020. BPA, bypassing agent; CFC, clotting factor concentrate; Q2M, every other month; SS, steady state. Source: Figure adapted with permission from Pipe et al. [62].

^aParticipants are eligible for dose escalation if >4 doses of fitusiran have been administered at the current dose level, and they experienced >2 predose antithrombin (AT) activity levels >35% (as per central laboratory) after their second dose at the current dose, and fitusiran administration and AT activity assessments occurred as per schedule at the current dose level.

^bParticipants previously escalated to a dose of 20 mg every month (QM), 50 mg QM or 80 mg QM due to AT >35% who experience >1 AT activity level <15% within a 12 month period must either permanently discontinue fitusiran prophylaxis, or in consultation with the Study Medical Manager may have the option to be de-escalated to their prior dose level.

^cStart of dosing after de-escalation from higher dose to occur only after centrally measured AT levels ≥22%. Participants receiving fitusiran at a dose of 20 mg every other month who experience ≥1 AT activity level <15% (as per central laboratory) within a 12-month period must permanently discontinue fitusiran treatment.

^dParticipants with QM dosing bleeding episodes during the first 8 weeks at the current dose level or every other month dosing bleeding episodes during the first 12 weeks at the current dose level will not be considered for this judgment.