General Information

Takhzyro (lanadelumab-flyo) is a plasma kallikrein inhibitor (monoclonal antibody). Plasma kallikreinn is an enzyme which is chronically uncontrolled in people with hereditary angioedema.

Takhzyro is specifically indicated for prophylaxis to prevent attacks of hereditary angioedema in patients 2 years of age and older.

Takhzyro is supplied as an injection for subcutaneous administration.

The recommended starting dose for patients 12 years of age and older is 300 mg every 2 weeks. A dosing interval of 300 mg every 4 weeks is also effective and may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

The recommended dose is 150 mg/1 mL every four weeks in patients 2 to <6 years of age and every two weeks in patients 6 to <12 years of age.

Mechanism of Action

Takhzyro (lanadelumab-flyo) is a fully human monoclonal antibody (IgG1/κ-light chain) that binds plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Lanadelumab-flyo decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.

Clinical Trial Results

The FDA approval of Takhzyro was based on the Phase III multicenter, randomized, double-blind, placebo-controlled parallel-group study, HELP (Hereditary Angioedema Long-term Prophylaxis). The study included 125 adult and adolescent patients with Type I or II HAE who experienced at least one investigator-confirmed attack per 4 weeks during the run-in period. Patients were randomized into 1 of 4 parallel treatment arms, stratified by baseline attack rate, in a 3:2:2:2 ratio (placebo, Takhzyro 150 mg q4wks, Takhzyro 300 mg q4wks, or Takhzyro 300 mg q2wks by subcutaneous injection) for the 26-week treatment period. Takhzyro reduced the number of monthly HAE attacks an average of 87% (n=27) vs. placebo (n=41) when administered at 300 mg every two weeks and 73% (n=29) vs placebo (n=41) when administered at 300 mg every four weeks. In the 26-week clinical study, patients taking Takhzyro 300 mg every 2 weeks also had 83% fewer moderate to severe attacks, and 87% fewer attacks that needed on-demand treatment. A pre-specified, exploratory analysis showed that 44% of patients (n=27) receiving Takhzyro 300 mg every two weeks had zero attacks compared to placebo (2%, n=41) for the 26-week treatment period from Day 0 to Day 182. Additionally, in a post hoc analysis of the 16-week period from Day 70 to Day 182, 77% of patients (n=26) treated with Takhzyro in the same dosage arm of the trial were attack-free compared to placebo (3%, n=37).