Berotralstat reduces HAE attacks regardless of baseline attack rates, prior treatment

Subgroup analyses of the phase III APeX-2 trial presented at AAAAI 2021 showed that use of the oral plasma kallikrein inhibitor berotralstat led to consistent reductions in attack frequency in patients with hereditary angioedema (HAE), irrespective of baseline attack rates and prior prophylaxis.

 

HAE is a rare, potentially life-threatening disorder that is characterized by episodic, unpredictable attacks of cutaneous angioedema, severe abdominal pain, and airway obstruction, which may recur frequently if left untreated. [N Engl J Med 2020;382:1136-1148; Ann Med 2016;48:256-267]

 

A post hoc analysis sought to determine whether baseline attack frequency influenced responder rates with berotralstat. A total of 121 patients were randomized to berotralstat 110 mg or 150 mg, or placebo, daily for 24 weeks. Participants were stratified into three cohorts according to the number of monthly HAE attacks: <2, ≥2 to <4, and ≥4 attacks/month (cohorts 1, 2, and 3, respectively). The findings reported herein are from the berotralstat 150 mg and placebo arms. [AAAAI 2021, abstract 066]

 

Compared with baseline, median monthly attack rates with berotralstat 150 mg dropped across all cohorts (from 1.3 to 0.41, from 2.7 to 1.2, and from 5.2 to 1.9 attacks/month for cohorts 1, 2, and 3, respectively).

 

Although the placebo arm also saw reductions of monthly baseline attack rates (from 1.7 to 1.3, from 3.1 to 2.7, and from 4.5 to 2.5 attacks/month for cohorts 1, 2, and 3, respectively), these rates were still higher compared with those observed with berotralstat 150 mg.

 

Treatment with berotralstat 150 mg led to a ≥50-percent relative reduction in attack rates in 70, 55, and 50 percent of participants in the respective cohorts 1, 2, and 3. The rest of the participants in cohorts 2 and 3 (45 percent and 50 percent, respectively) saw ≥70-percent relative reduction in attack rates with berotralstat 150 mg.

 

“These results demonstrate consistent responder rates with berotralstat, adding a potential oral prophylactic option to the treatment armamentarium of physicians,” said the researchers.

 

Three-quarters of participants on berotralstat 150 mg and 73 percent of those on placebo had prior prophylactic treatment. In another subgroup analysis, responder rates were evaluated according to the type of prior prophylaxis received: C1 esterase inhibitor (C1-INH), androgen, and no prophylaxis. [AAAAI 2021, abstract 070]

 

Among participants with history of C1-INH prophylaxis or androgen use, use of berotralstat 150 mg led to significant reductions in HAE attacks compared with placebo (1.58 vs 2.84 attacks/month, p=0.012 [C1-INH] and 1.35 vs 2.60 attacks/month; p<0.001 [androgen]).

 

Berotralstat 150 mg recipients with no history of prophylaxis also had reductions in HAE attacks compared with placebo (0.86 vs 1.78 attacks/month; p=0.056).

 

These findings suggest that prior prophylactic treatment, or the lack thereof, did not appear to influence the efficacy of berotralstat 150 mg in reducing HAE attacks, noted the researchers.

 

The findings in these subgroup analyses augment the initial findings of APeX-2 showing improved patient-reported quality of life and satisfaction with berotralstat. [Ann Allergy Asthma Immunol 2020;125:S22; Ann Allergy Asthma Immunol 2020;125:S25] Collectively, these findings reinforce the potential of oral berotralstat as a valuable treatment alternative in the management and prevention of HAE.