Oral Prophylaxis With Berotralstat (Bcx7353) Reduces Use Of Standard Of Care (Soc) On-Demand Medication In Patients With Hereditary Angioedema (Hae): Apex-2 Study Results

Berotralstat is a once-daily oral inhibitor of plasma kallikrein in development for prophylaxis of HAE. The Phase 3, randomized, double-blind, placebo-controlled APeX-2 study (NCT03485911) evaluated the efficacy of berotralstat over a 24-week period. The use of SOC on-demand medications during this study was evaluated. Subjects with HAE Type 1/2 with ≥2 attacks in the 14-56 day baseline period were randomized 1:1:1 to receive berotralstat 150mg or 110mg or placebo for 24 weeks. Subjects were to treat any HAE attacks occurring on study in accordance with their usual acute treatment plan. Investigator-confirmed HAE attacks and SOC on-demand medication use over 24 weeks were analyzed. The HAE attack rate was significantly lower in both berotralstat dose groups compared to placebo (150 mg, -44.2%, p<0.001; 110mg, -30.0%, p=0.024, primary endpoint). The rate of attacks requiring treatment was also significantly lower in both berotralstat dose groups compared to placebo (150mg, -49.2%, nominal p<0.001; 110mg, -36.9%, nominal p=0.015). The rate of use of SOC on-demand medications was significantly reduced in both the 150mg (-53.6%, nominal p<0.001) and the 110mg (-46.3%, nominal p=0.002) dose groups compared to placebo, which was larger than the observed reduction in attack rate. Berotralstat was generally safe and well-tolerated. Berotralstat at 150mg QD significantly reduced the rate of attacks, attacks requiring treatment, and to a greater extent, the rate of SOC on-demand medication use relative to placebo in the APeX-2 study, suggesting reduced attack severity on berotralstat. These represent key features of successful HAE prophylaxis.