TAKHZYRO SIDE EFFECTS
- Generic Name: lanadelumab-flyo injection
- Brand Name: Takhzyro
SIDE EFFECTS
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.
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 (%) | |
| Injection site reactionsa | 14 (34) | 16 (57) | 13 (45) | 15 (56) | 44 (52) |
| Upper respiratory infectionb | 13 (32) | 3 (11) | 9 (31) | 12 (44) | 24 (29) |
| Headachec | 9 (22) | 3 (11) | 6 (21) | 9 (33) | 18 (21) |
| Rashd | 2(5) | 2 (7) | 3 (10) | 1 (4) | 6 (7) |
| Myalgia | 0 | 1 (4) | 0 | 3 (11) | 4 (5) |
| Dizziness | 0 | 1 (4) | 3 (10) | 1 (4) | 5 (6) |
| Diarrhea | 2 (5) | 3 (11) | 0 | 1 (4) | 4 (5) |
| N= number of patients; n =number of patients experiencing the event; q2wks = every 2 weeks; q4wks = every 4 weeks a Injection site reactions include: pain, erythema, bruising, hematoma, hemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, edema and rash. b Includes upper respiratory infection, viral upper respiratory infection c Includes headache, tension headache, sinus headache d Includes rash, rash maculopapular, rash erythematous |
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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 ongoing 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 >2x ULN. One TAKHZYRO-treated patient permanently discontinued treatment due to elevated transaminases (4.1x ULN AST). None of the patients were reported to have serious adverse reactions of elevated transaminases.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to lanadelumab-flyo in the study described below with the incidence of antibodies in other studies or to other products may be misleading.
In Trial 1, 10 (12%) lanadelumab-flyo-treated and 2 (5%) placebo-treated patients had at least 1 anti-drug antibody (ADA)-positive sample during the treatment period; antibody titers were low (range: 20 to 1280). The ADA response observed was transient in 2/10 lanadelumab-flyo and 1/2 placebo-treated patients. Pre-existing low titer antibodies were observed in 3 lanadelumab-flyo-treated patients and 1 placebo-treated patient with ADAs. Two patients receiving 150 mg q4wks had low titer antibodies classified as neutralizing.
The development of ADA including neutralizing antibodies against lanadelumab-flyo did not appear to adversely affect pharmacokinetics (PK), pharmacodynamics (PD), safety or clinical response.
SRC: NLM .