TAKHZYRO

6 ADVERSE REACTIONS The most common adverse reactions (≥10%) are injection site reactions, upper respiratory infections, headache, rash, dizziness, diarrhea, and myalgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult and Pediatric Patients 12 Years of Age and Older The safety of TAKHZYRO is primarily based on a 26-week, randomized, double-blind, parallel-group and placebo-controlled study (Trial 1) in 125 patients with Type I or II HAE. Eligible patients were also able to participate in an open-label extension study (Trial 2) up to 130 weeks. In Trial 1, a total of 84 patients with HAE aged 12 years and older received at least one dose of TAKHZYRO. Overall, 70% of patients were female and 90% of patients were Caucasian with a mean age of 41 years. The proportion of patients who discontinued study drug prematurely due to adverse events was 1.2% for TAKHZYRO-treated patients and 4.9% for placebo-treated patients. No deaths occurred in the trial. The safety profile of TAKHZYRO was generally similar across all subgroups of patients, including analysis by age, sex, and geographic region. Table 1 shows adverse reactions occurring in ≥10% of patients in any TAKHZYRO treatment group that also occurred at a higher rate than in the placebo treatment group in Trial 1. Table 1 Adverse Reactions Observed in ≥10% of Patients Treated with TAKHZYRO in Trial 1 Adverse Reaction Placebo (N=41) TAKHZYRO 150 mg q4wks (N=28) 300 mg q4wks (N=29) 300 mg q2wks (N=27) Total (N=84) n (%) n (%) n (%) n (%) n (%) N= number of patients; n =number of patients experiencing the event; q2wks = every 2 weeks; q4wks = every 4 weeks Injection site reactions Injection site reactions include: pain, erythema, bruising, hematoma, hemorrhage, pruritus, swelling, induration, paresthesia, reaction, warmth, edema and rash. 14 (34) 16 (57) 13 (45) 15 (56) 44 (52) Upper respiratory infection Includes upper respiratory infection, viral upper respiratory infection 13 (32) 3 (11) 9 (31) 12 (44) 24 (29) Headache Includes headache, tension headache, sinus headache 9 (22) 3 (11) 6 (21) 9 (33) 18 (21) Rash Includes rash, rash maculopapular, rash erythematous 2(5) 2 (7) 3 (10) 1 (4) 6 (7) Dizziness 0 1 (4) 3 (10) 1 (4) 5 (6) Diarrhea 2 (5) 3 (11) 0 1 (4) 4 (5) Myalgia 0 1 (4) 0 3 (11) 4 (5) Injection site reactions primarily consisted mainly of pain, erythema, and bruising at the injection site. There was no meaningful difference in injection site reactions with self-administration. Less Common Adverse Reactions Other adverse reactions that occurred at a higher incidence in TAKHZYRO-treated patients compared to placebo include hypersensitivity (1% vs 0%), increased aspartate transaminase (2% vs 0%), and increased alanine transaminase (2% vs 0%). Safety data from the open-label extension study, consisting of 109 rollover patients from Trial 1 and 103 non-rollover HAE patients, is consistent with controlled safety data from Trial 1. Laboratory Abnormalities Transaminase elevations During the placebo-controlled treatment period in Trial 1, the number of TAKHZYRO-treated patients with maximum transaminase (ALT or AST) levels >8, >5, or >3 times the upper limit of normal (ULN) was 1 (1.2%), 0 (0%), or 3 (3.6%) respectively, compared to 0 in the placebo-treated patients. These transaminase elevations were asymptomatic and transient. No patients had elevated total bilirubin >2× ULN. One TAKHZYRO-treated patient permanently discontinued treatment due to elevated transaminases (4.1× ULN AST). None of the patients were reported to have serious adverse reactions of elevated transaminases. Pediatric Patients 2 to Less Than 12 Years of Age The safety of TAKHZYRO was evaluated at 150 mg/mL (150 mg q4wks for patients 2 to <6 years or 150 mg q2wks with the option for 150 mg q4wks if the patient is well-controlled for 6 months for patients 6 to <12 years) in an open-label, multicenter study with 21 patients aged 2 to less than 12 years. No new safety signals were observed in these patients.