Efficacy and safety of lanadelumab were characterized in the HELP Study and open-label extension (OLE). Final OLE results are presented.

Berotralstat is an oral once-daily plasma kallikrein inhibitor in development for hereditary angioedema (HAE) attack prophylaxis. Berotralstat significantly reduced HAE attack rates and was safe and generally well tolerated in Part 1 of the Phase 3 APeX-2 study (NCT03485911). This analysis evaluated quality of life (QoL) as measured by the Angioedema QoL (AE-QoL) questionnaire.

BACKGROUND: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. OBJECTIVE: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). METHODS: Eligible patients were >= 12 years with >= 2 monthly attacks prescreening or preelong-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction >= 50%, attack severity, number of attack-free days, and safety. RESULTS: Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Leastsquares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P <.0001). Most patients had circle plus 50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INHetreated patients were attackfree and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). CONCLUSIONS: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Hereditary angioedema (HAE) is a potentially life-threatening disorder in which C1-esterase inhibitor, which inhibits kallikrein, is low or non-functioning. All current targeted prophylactic treatments for HAE are parenteral. The safety profile of BCX7353, a novel oral kallikrein inhibitor for HAE prophylaxis, was evaluated in a Phase 3 trial (APeX-2; NCT03485911).

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. Symptoms are central to the diagnosis and therapeutic outcomes of EoE. The Dysphagia Symptom Questionnaire (DSQ) is the only daily instrument validated for the symptoms of EoE. This study examined the efficacy of budesonide oral suspension (BOS; SHP621) on dysphagia in patients with EoE.

Lanadelumab safety over 26 weeks at doses up to 300 mg every 2 weeks (Q2W) was evaluated in the HELP study. The long-term safety of lanadelumab is being assessed in the ongoing HELP open-label extension study (OLE; NCT02741596).

Introduction Lanadelumab, a fully human monoclonal antibody targeting plasma kallikrein, effectively prevented attacks in patients with hereditary angioedema (HAE) in the phase 3 HELP Study (NCT02586805). Methods In HELP, patients ≥12 years with type I/II HAE and ≥1 attack during a 4-week run-in received SC lanadelumab 300 mg q2wks, 300 mg q4wks, 150 mg q4wks, or placebo over 26 weeks. The safety and immunogenicity of repeated doses of lanadelumab were assessed. Results The safety population consisted of 125 patients who received ≥1 dose of study medication; 84 received lanadelumab and 41 received placebo. 78 [92.8%] and 35 [85.4%] patients in lanadelumab and placebo arms completed the study. Treatment emergent AEs (TEAEs) were reported by 76 (90.5%) patients receiving lanadelumab and 31 (75.6%) patients receiving placebo. No serious treatment-related AEs or deaths were reported. One (1.2%) lanadelumab-treated subject had two related hypersensitivity events, one mild and one moderate in severity. Immunogenicity results included ten (11.9%) lanadelumab-treated subjects and 2 (4.9%) placebo-treated subjects with ≥1 treatment-emergent anti-drug antibody (ADA)-positive sample, all at low titers. Two (2.4%) subjects positive for ADA in the 150 mg q4wks arm had low titer neutralizing antibodies. The development of ADA did not impact pharmacokinetics, pharmacodynamics, or clinical response. No safety signals in terms of clinical laboratory tests, vital signs, physical examinations, or ECGs were identified. Conclusions Lanadelumab was generally well tolerated, with few cases of hypersensitivity and low immunogenicity. Together with its efficacy in preventing HAE attacks, lanadelumab may offer patients a novel and well tolerated therapeutic option for HAE prophylaxis.

Introduction Lanadelumab significantly reduced hereditary angioedema (HAE) attack rates versus placebo over 26 weeks in the phase 3 double-blind (DB) HELP Study (NCT02586805). Patients who completed the DB continued into the ongoing open-label extension study (OLE; NCT02741596). This interim analysis of data from 26May2016-01Sept2017 evaluated lanadelumab efficacy in the OLE among patients who received placebo in the DB. Methods Patients from the DB placebo group received a single 300 mg lanadelumab dose on Day 1 of the OLE. Following their first attack, they received lanadelumab 300 mg every 2 weeks. Results 33 patients from the DB placebo group entered the OLE. Their median time on study in the OLE was 8.6 months (range 6.6-12.6 months); all patients completed ≥6 months’ time on study, and 14 (42.4%) patients completed ≥9 months. During the DB run-in and treatment periods, patients had a median attack rate of 2.90 and 1.82 attacks/month, respectively (Figure). During the OLE, the median attack rate was 0.10 attacks/month. The median change in attack rate between the DB and OLE treatment periods was −1.38 attacks/month (−98.5%). Conclusions Consistent with the DB results, there was a significant reduction in attack rate with lanadelumab treatment among patients who previously received placebo. Attack rates in the DB and OLE studies