The FSA approves lanadelumab (Takhzyro), the first monoclonal antibody approved in the United States to treat patients 12 years and older with types I and II hereditary angioedema.
This afternoon, August 23, 2018, the US Food and Drug Administration (FDA) approved the first monoclonal antibody, Shire Pharmaceutical’s lanadelumab (Takhzyro, SHP643), for the treatment of types I and II hereditary angioedema (HAE) in patients aged 12 years and older.
Used to prevent swelling attacks from occurring, lanadelumab is a plasma kallikrein inhibitor.
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study in 125 patients with HAE served as the basis for the approval. For a 26-week treatment period, lanadelumab was evaluated in patients with HAE type I and II aged ≥ 12 years of age, who were split into 3 dosing arms: those would would receive 150 mg or 300 mg every 4 weeks; those who would receive 300 mg every 2 weeks; and those who would receive placebo.
Over a 6-month treatment period, clinically meaningful and statistically significant reductions in the rate of investigator-confirmed HAE attacks experienced by patients administered lanadelumab compared with those who received placebo were observed. In addition, primary and all secondary endpoints for all lanadelumab (subcutaneous injection) treatment arms versus placebo were met. Lanadelumab proved effective regardless of baseline attack frequency and demonstrated a meaningful reduction starting from the first dose throughout the 26-week treatment period. Compared with placebo, a significantly higher proportion of patients were also attack-free throughout the entire 26-week study period.
Furthermore, a favorable safety profile was observed with no occurrences of treatment-related serious adverse events. Mild to moderate injection site pain (29% placebo versus 43% across all lanadelumab arms) was the most commonly noted treatment-emergent adverse event.
Injection site reactions, upper respiratory infections, headache, rash, muscle pain, dizziness, and diarrhea were the most common adverse drug reactions experienced by patients who had received lanadelumab in clinical trials.
Lanadelumab also has the potential to significantly reduce the current prophylaxis treatment burden. Unlike C1 esterase inhibitor [human] (Cinryze), which is an intravenous injection of a higher volume that requires reconstitution, lanadelumab is a subcutaneous injection of a small volume that can be self-administered once or twice a month.
Previously, a priority review, breakthrough therapy designation, and orphan drug designation were granted to lanadelumab by the FDA. An orphan drug designation was also granted to lanadelumab by the European Union.
Accounting for 85% of cases, HAE type I affects an estimated 1 in 50,000 men and women. Typically, HAE symptoms originate in childhood and worsen following puberty.