Berotralstat shows promise in preventing hereditary angioedema attacks

Once-daily berotralstat, an oral inhibitor of plasma kallikrein, suppresses hereditary angioedema (HAE) attacks without posing strong safety concerns, a recent study has found.

The researchers conducted a double-blind, parallel-group study including 120 participants randomized to receive 110- (n=41) or 150-mg (n=40) berotralstat or placebo (n=39). Participants were eligible if they had confirmed HAE due to C1 inhibitor deficiency and had at least two HAE attacks in a 56-day run-in period. Primary outcome was the rate of attacks in the 24-week treatment period.

Placebo participants had an estimated, investigator-confirmed monthly HAE attack rate of 2.35 throughout the 24 weeks of observation. In comparison, the 110-mg berotralstat dose yielded a significantly lower attack rate of 1.65 (attack rate ratio, 0.70, 95 percent confidence interval [CI], 0.51–0.95; p=0.024). The 150-mg dose likewise suppressed HAE attacks significantly vs placebo (attack rate: 1.31; attack rate ratio, 0.56, 95 percent CI, 0.41–0.77; p<0.001).

Treatment-emergent adverse events (TEAEs) were reported in 83 percent and 85 percent of the 110- and 150-mg berotralstat dose groups, respectively. In the placebo arm, 77 percent experienced TEAEs. The most common TEAEs were abdominal pain, vomiting, diarrhoea, and back pain.

Serious TEAEs were documented in one patient in the 110-mg berotralstat arm and three patients in the placebo group, none of which were deemed drug-related. However, three drug-related grade 3 or 4 AEs were documented, all in the 110-mg arm.

“The combination of efficacy, safety, and tolerability with convenient oral, once-daily dosing will make berotralstat an important addition to the HAE–C1-inhibitor therapeutic armamentarium,” the researchers said.