- D1.337 - Long-Term Safety, Tolerability, and Effectiveness of Berotralstat in Hereditary Angioedema: Interim Analysis of the APeX-N Post-Authorization Study

Berotralstat is an oral plasma kallikrein inhibitor approved for long-term propylaxis (LTP) of hereditary angioedema (HAE) attacks. APeX-N is a post-authorization safety study (PASS) evaluating long-term safety, tolerability, and effectiveness of berotralstat in a real-world setting.

APeX-N is a multicenter, single-arm, non-interventional PASS conducted across Europe and will follow patients for up to 5 years following prospective and retrospective enrolment. Eligible patients with confirmed diagnosis of HAE receive berotralstat per approved label. Demographics, medical history and 6-month attack prior to consent were collected at baseline; all other data were recorded during the observation period, defined as the time from study consent to most recent visit under routine clinical practice. This analysis presents data from APeX-N patients treated with berotralstat for ≥2 years.

To date, 56/164 enrolled patients (3 adolescents, 53 adults) have reached ≥2 years of berotralstat treatment. Mean age was 40 years (range 13–77), 53.6% were female, and 78.6% reported a family history of HAE. Mean age at diagnosis was 17.2 years (SD 9.45). Before berotralstat 66.1% had at least one prior LTP (35.7% tranexamic acid, 32.1% danazol, 21.4% C1-Inhibitor concentrate). The mean time between treatment initiation and the start of observational data collection was 1.75 years (SD 0.74), and mean observation period duration was 1.20 years (SD 0.57). Mean baseline monthly attack rate in the 6 months before berotralstat (n=43) was 2.41 (median 2.00). During observation, 40 patients had ≥1 follow-up visit; their mean monthly attack rate was 0.35 (median 0.20).

Treatment-emergent adverse events occurred in 2/56 patients (3.6%), including 3 mild gastrointestinal disorders and 1 mild hypertension. Special situations were reported in 5 patients (8.9%): drug ineffective (n=2, 3.6%), medication errors (n=2, 3.6%), and dose omission (n=1, 1.8%). These findings are consistent with overall population (n=164) safety data representing cumulative berotralstat exposure of 293.6 person-years. Predominantly mild, non-serious adverse drug reactions were reported in 12 patients, leading to discontinuation in one patient and no related serious adverse events.

After ≥2 years of berotralstat treatment, patients maintained low HAE attack frequency and few, self-limiting adverse events. These real-world findings support suitability of berotralstat for LTP of HAE.