Once-daily oral berotralstat for long-term prophylaxis of hereditary angioedema: The open-label extension of the APeX-2 randomized trial.

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients ≥12 years.

OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat.

METHODS: APeX-2 was a Phase 3, parallel-group, multicenter trial in patients with HAE caused by C1 inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg berotralstat over 24 weeks. In Part 2, berotralstat-treated patients continued the same treatment and placebo-treated patients were re-randomized to 150 or 110 mg berotralstat for 24 weeks. In Part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In Part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL).

RESULTS: Eighty-one patients entered Part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n=70), mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/month. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain.

CONCLUSION: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks, and improved QoL over 96 weeks.