Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study

Abstract

Background: The aim was to evaluate long-term effectiveness and safety of lanadelumab in patients ≥12 y old with hereditary angioedema (HAE) 1/2 (NCT02741596).

Methods: Rollover patients completing the HELP Study and continuing into HELP OLE received one lanadelumab 300 mg dose until first attack (dose-and-wait period), then 300 mg q2wks (regular dosing stage). Nonrollovers (newly enrolled) received lanadelumab 300 mg q2wks from day 0. Baseline attack rate for rollovers: ≥1 attack/4 weeks (based on run-in period attack rate during HELP Study); for nonrollovers: historical attack rate ≥1 attack/12 weeks. The planned treatment period was 33 months.

Results: 212 patients participated (109 rollovers, 103 nonrollovers); 81.6% completed ≥30 months on study (mean [SD], 29.6 [8.2] months). Lanadelumab markedly reduced mean HAE attack rate (reduction vs baseline: 87.4% overall). Patients were attack free for a mean of 97.7% of days during treatment; 81.8% and 68.9% of patients were attack free for ≥6 and ≥12 months, respectively. Angioedema Quality-of-Life total and domain scores improved from day 0 to end of study. Treatment-emergent adverse events (TEAEs) (excluding HAE attacks) were reported by 97.2% of patients; most commonly injection site pain (47.2%) and viral upper respiratory tract infection (42.0%). Treatment-related TEAEs were reported by 54.7% of patients. Most injection site reactions resolved within 1 hour (70.2%) or 1 day (92.6%). Six (2.8%) patients discontinued due to TEAEs. No treatment-related serious TEAEs or deaths were reported. Eleven treatment-related TEAEs of special interest were reported by seven (3.3%) patients.

Conclusion: Lanadelumab demonstrated sustained efficacy and acceptable tolerability with long-term use in HAE patients.

Keywords: HAE; HAE attacks; HELP OLE; hereditary angioedema; lanadelumab; long-term prophylaxis.

FIGURE 1

Patient disposition. ^†The category “withdrawal by patient” also included patients who transitioned to the commercial product (n = 117); see Table S1. ^‡The number of patients who completed the study (n = 173) includes patients who transitioned to the commercial product (n = 117), as well those who remained in the study for its entire duration (n = 56). AE, adverse event; q2wks, every 2 weeks; q4wks, every 4 weeks

FIGURE 2

HAE attack reduction (A), responder analysis (B), and percentage of patients with maximum attack‐free period ≥6 months or ≥12 months (C). (A) Values above bars are mean attack rates. Mean change from baseline and mean (minimum, maximum) percentage change from baseline are shown. Baseline data were not available for nonrollover patients’ HAE attacks requiring acute treatment or for their high‐morbidity attacks. n values represent the number of patients with attack rate data during the treatment period. Three rollover patients who discontinued the study during the dose‐and‐wait period were not included in the analyses. Analyses were performed based on reported HAE Attack Assessment and Reporting Procedures severity, as follows: Mild—Transient or mild discomfort; Moderate—Mild to moderate limitation in activity, some assistance needed; Severe—Marked limitation in activity, assistance required. High‐morbidity attacks were defined as any attack that had ≥1 of the following characteristics: severe, resulted in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure <90 mmHg, required intravenous hydration, or associated with syncope/near‐syncope), or laryngeal involvement. (B) For each patient, the percentage reduction was calculated as the baseline attack rate minus the treatment period attack rate (regular dosing stage for rollover patients) divided by the baseline attack rate, multiplied by 100. Patients may appear in >1 group as applicable, based on their percentage reduction. Patients who had an attack rate of zero at baseline were excluded from the analysis. HAE, hereditary angioedema; q2wks, every 2 weeks

FIGURE 3

Time to first HAE attack during the dose‐and‐wait period (rollover safety population). Open circles on the lines refer to censored patients—those who discontinued the study prior to having an attack. HAE, hereditary angioedema; q2wks, every 2 weeks; q4wks, every 4 weeks