Berotralstat 150mg capsules

BACKGROUND: With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. METHODS: APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period. RESULTS: Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%). CONCLUSIONS: Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.

Abstract licence: CC BY-NC-ND 4.0

Abstract Hereditary angioedema (HAE) is a condition characterized by episodes of cutaneous and submucosal edema. Angioedema of the extremities and abdominal attacks are the most common manifestations of the disease. It can also affect the upper airways with the potential of becoming life-threatening. The two most common causes of HAE are a deficiency of C1 inhibitor (classified as type 1 HAE) or a dysfunction of C1 inhibitor (type 2 HAE). A malfunction or deficiency of C1 inhibitor leads to an overactivated plasma kallikrein (an inflammatory vasoactive peptide), that increases bradykinin, mediating the angioedema episodes in patients with HAE. To minimize the difficulties of this pathology and to improve patients’ quality of life, prevention of this condition is essential. Berotralstat is a unique option for oral administration for routine prophylaxis. This drug acts by binding to kallikrein and reducing its plasma activity, lowering bradykinin levels. Open-label studies have demonstrated the effectiveness of a single daily dose of berotralstat 150 mg in preventing HAE attacks. This review aims to examine studies performed to elucidate the efficacy, safety, and tolerability of berotralstat.

Abstract licence: CC BY-NC 3.0