Relationship Between Body Weight, PK/PD, and Attack Responses Following Subcutaneous Administration of Lanadelumab in Patients with Hereditary Angioedema

Abstract

6 CSL Behring, King of Prussia, PA. RATIONALE: Hereditary angioedema (HAE) due to C1-esterase inhibitor (C1-INH) deficiency is known to have a significant negative impact on patients' health-related quality of life (HRQoL). We evaluated the impact of long-term prophylaxis with subcutaneous C1-INH ([C1-INH (SC)] Haegarda Ò , CSL Behring) on HRQoL in HAE patients treated in an openlabel extension (OLE) of the pivotal phase III COMPACT trial.METHODS: In the OLE, patients with > _4 HAE attacks within a consecutive 2-month period (N5126) self-administered C1-INH (SC) 40 or 60 IU/kg twice weekly for up to 52 or 140 weeks (US only). HRQoL was self-assessed by patients at various points during the OLE using several instruments, including the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, Hospital Anxiety and Depression Scale (HADS), and Work Productivity and Activity Impairment (WPAI) assessment. RESULTS: With C1-INH (SC) 60 IU/kg, significant improvements from baseline to the end-of-study visit were observed on the EQ-5D, HADS, and 3 of 4 WPAI domains. Clinically meaningful improvements versus baseline (mean [95% CI]) were observed on the Health State Value (0.07 [0.01, 0.12]) and Visual Analogue Scale (7.45 [3.29, 11.62]) of the EQ-5D. Improvements were also noted on the HADS Depression (-0.95 [-1.57, -0.34]) and Anxiety (-1.23 [-2.08, -0.38]) scales and WPAI domains of Presenteeism (-23.33 [-34.86, -11.81]), Work Productivity Loss (-26.68 [-39.92, -13.44]), and Activity Impairment (-16.14 [-26.36, -5.91]). CONCLUSIONS: Long-term prophylaxis with C1-INH (SC) leads to significant and clinically meaningful improvements in various HRQoL measures in patients with HAE. J ALLERGY CLIN IMMUNOL FEBRUARY 2019 AB38 Abstracts SATURDAY

<p>Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy</p>

“…In order to evaluate the relationship between body weight, pharmacokinetics/pharmacodynamics and clinical endpoints, data from 84 patients treated with lanadelumab 150 mg every 4 weeks, 300 mg every 4 weeks or 300 mg every 2 weeks for 6 months in the HELP Study were analyzed. The results of the analysis showed that lanadelumab plasma concentrations remained markedly above the IC50 across a large range of body weight (with associated cHMWK inhibition), particularly for the 300 mg every 2 weeks regimen, with a good safety and tolerability profile 37. Interim results from the HELP Open-Label Extension Study show that treatment with lanadelumab 300 mg every 2 weeks led to a significant decrease of HAE attack rate compared with 3-month historical experience in patients with and without prior C1-INH long-term prophylaxis 38.…”