# Attack rate reductions following berotralstat initiation among US patients with hereditary angioedema in the real-world

## TL;DR

Berotralstat significantly reduces HAE attack rates in patients, regardless of their initial attack frequency, according to a real-world study.

## Contribution

This study provides real-world evidence of sustained attack rate reductions with berotralstat in HAE patients across different baseline frequencies.

## Key findings

- Attack rates decreased significantly from 2.50 to 0.79 attacks/month in HAE-C1INH patients after 12 months of berotralstat.
- Patients with zero baseline attacks/month maintained low attack rates following berotralstat initiation.
- Sustained reductions in attack rates were observed at 18 months of treatment in both HAE-C1INH and HAE-nC1INH patients.

## Abstract

Hereditary angioedema (HAE) causes recurring swelling attacks, leading to substantial disease burden. This real-world, retrospective study aimed to evaluate HAE attack rates before and after berotralstat initiation stratified by patients’ baseline attack frequency.

Specialty Pharmacy data from Optime Care, Inc. (12/2020–01/2024), the sole berotralstat dispenser in the United States, were analyzed. Eligible patients had  ≥ 2 berotralstat dispensings (first =  index) and ≥ 1 self-assessment of attacks at baseline (90-days pre-index) and follow-up (first-to-last dispensing). Patients were classified by HAE type (based on laboratory measurements) and baseline attacks (≥ 5, 2–4, 1, and 0 attacks/month). Follow-up attack rates were compared with baseline using mean differences, confidence intervals, and P-values. Among those with 0 baseline attacks/month, proportions with 0 follow-up attacks/month were assessed.

Of 390 eligible patients with HAE with C1 esterase inhibitor (C1INH) deficiency (HAE-C1INH) and 311 with HAE with normal C1INH (HAE-nC1INH), most were female (64.1% and 77.5%) with mean ages of 39.3 and 48.1 years, respectively. Mean attack rates decreased from 2.50 to 0.79 attacks/month (HAE-C1INH) and from 4.59 to 1.68 attacks/month (HAE-nC1INH) at 12-months of berotralstat treatment (both P < 0 .001), with sustained reductions at 18-months. Patients with ≥ 1 baseline attack/month experienced significantly lower attack rates after berotralstat initiation. Among patients with 0 baseline attacks/month, most also maintained 0 attacks/month in each follow-up interval (HAE-C1INH: 70–85%; HAE-nC1INH: 61–81%).

Berotralstat was associated with significant and sustained reductions in attack rates among patients with HAE, regardless of baseline attack rate. Patients with 0 baseline attacks/month maintained low attack rates following berotralstat initiation.

The online version contains supplementary material available at 10.1186/s13223-025-01005-x.

Hereditary angioedema (HAE) is a rare genetic condition characterized by sudden episodes of swelling in various parts of the body. The swelling can be extremely painful and interrupt daily activities when it occurs in areas such as hands, feet, intestines, or genitals, and potentially fatal in cases of airway swelling. Berotralstat is an oral medication that can prevent HAE attacks. In this study, people diagnosed and living with HAE had fewer HAE attacks after starting berotralstat. When they were grouped based on the frequency of HAE attacks they had before starting treatment, berotralstat decreased the rate of HAE attacks in all groups. Our research supports that berotralstat treatment helps to reduce HAE attacks and should be considered as a treatment option regardless of the number of HAE attacks people are experiencing.

The online version contains supplementary material available at 10.1186/s13223-025-01005-x.