Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks

Abstract

Background: Lanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.

Objective: To assess time to onset of effect and long-term efficacy of lanadelumab, based on exploratory findings from the HELP Study.

Methods: Eligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0-69 findings using a Poisson regression model accounting for overdispersion. Least-squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0-69 versus steady state (days 70-182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.

Results: One hundred twenty-five patients were randomized and treated. During days 0-69, mean monthly attack rate was significantly lower with lanadelumab (0.41-0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33-0.61 vs 1.66) and moderate/severe attacks (0.31-0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%-48.1% vs 7.3%) and responders (85.7%-100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0-69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable-HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0-69 and 70-182.

Conclusion: Protection with lanadelumab started from the first dose and continued throughout the entire study period.

Keywords: durable efficacy; hereditary angioedema; long-term prophylaxis; onset of action.

FIGURE 1

Investigator‐confirmed hereditary angioedema attack rate during days 0‐69 of treatment. A, Monthly rate of all attacks (primary endpoint). B, Monthly rate of attacks requiring acute treatment. C, Monthly rate of moderate/severe attacks

FIGURE 2

Rate of hereditary angioedema attacks during days 0‐69 of treatment and during the steady‐state period. Attack rates were based on attacks occurring within 2 wk prior to each time point. A month is defined as 28 d. Error bars indicate the standard error of the mean

FIGURE 3

Attacks by maximum severity, days 0‐69 of treatment. Due to rounding, some bars may not total 100%

FIGURE 4

Proportion of patients achieving ≥50% to ≥90% reduction in attack rate during days 0‐69 relative to the run‐in period. Responders were defined as patients who achieved ≥50% reduction in number of attacks relative to the run‐in period. For each patient, the percentage reduction was calculated as the run‐in period attack rate minus the treatment period attack rate divided by the run‐in period attack rate, multiplied by 100. The percentage reduction groups are not mutually exclusive; patients may appear in more than one group, as applicable, based on their percentage reduction

FIGURE 5

Agreement in findings for maximum attack severity during days 0‐69 (D0‐69) vs the steady‐state (SS) period. The Kappa statistic (κs) was used to assess the magnitude of agreement in findings between the two treatment periods. Kappa statistics are interpreted using the following scale: 1=perfect agreement (precision/reliability); 0=agreement fully by chance; 0.01‐0.20=slight agreement; 0.21‐0.40=fair agreement; 0.41‐0.60=moderate agreement; 0.61‐0.80=substantial agreement; 0.81‐0.99=almost perfect agreement. ²⁴ Due to rounding, some bars may not total 100%. Subjects were included if they had both Day 0‐69 and Day 70‐182 results