Pooled safety data
Adverse reactions (ARs) from pooled clinical studies with HEMLIBRA® (N=189)*
Cases of TMA and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more while taking HEMLIBRA
ARs reported in ≥5% of patients
- Most common ARs (at least 10%) were ISR (19%), headache (15%), and arthralgia (10%)‡
- All ISRs were reported as mild-to-moderate in intensity; 88% resolved without treatment
- The median duration of exposure across the studies was 38 (0.8 to 177.2) weeks
- As with all therapeutic proteins, there is a potential for immunogenicity
- No patients tested positive for
anti-emicizumab antibodies in HAVEN 1 and HAVEN 2 (n=171)
- 4 patients tested positive for anti-emicizumab antibodies in the dose-finding trial (n=18)
- The anti-emicizumab antibody positive rate may be under-reported due to the limitation of the assay
Characterization of aPCC treatment§ in pooled clinical trials
A total of 125 instances of aPCC treatment in 36 patients treated with HEMLIBRA
§An instance of aPCC treatment was defined as all doses
of aPCC received by a patient, for any reason, until there was a
36-hour treatment-free break.
3 TMA cases in HAVEN 1
- Evidence of improvement was seen within 1 week following discontinuation of aPCC
- One patient elected to resume HEMLIBRA following resolution of TMA
2 thrombotic events in HAVEN 1
- No thrombotic events required anticoagulation therapy
- Evidence of improvement or resolution was seen within 1 month following discontinuation of aPCC
- One patient elected to resume HEMLIBRA following resolution of thrombotic events
HEMLIBRA increases the potential for blood to clot. Therefore, it’s important to discuss with patients the use of bypassing agents prior to starting HEMLIBRA prophylaxis.
aPCC=activated prothrombin complex concentrate;
*Based on pooled data from a randomized trial (HAVEN 1), single-arm trial (HAVEN 2), and a dose-finding trial, in which a total of 189 male patients with hemophilia A received at least one dose of HEMLIBRA as routine prophylaxis. 94 patients (50%) were adults (aged 18 years and older), 38 (20%) were adolescents (aged 12 to under 18 years), 55 (29%) were children (2 years to under 12 years), and two (1%) were infants (1 month to under 2 years). 7 of the 189 patients (4%) included in the safety population were patients without FVIII inhibitors from the dose-finding trial.
†The most commonly reported ISR symptoms were injection-site erythema (7.4%), injection-site pruritus (5.3%), and injection-site pain (5.3%).
‡Includes injection site bruising, injection site discomfort, injection site erythema, injection site hematoma, injection site induration, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticarial, and injection site warmth.