D2.330 - Hereditary angioedema prophylaxis therapy: berotralstat and lanadelumab safety profile

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal dominant disorder caused by C1-INH deficiency (type I) or dysfunction (type II). Two effective long-term prophylaxis (LTP) approved for patients with HAE-C1INH are lanadelumab and berotralstat, which inhibit the same protein: kallikrein. They are administered subcutaneously every 2–4 weeks and orally daily.

Aim: To evaluate the demographic distribution of adverse drug reactions (ADR) of berotralstat and lanadelumab. Furthermore, we compared the relative distribution of the side effects for the two drugs, both acting through kallikrein block. 

the World Health Organization’s pharmacovigilance database of individual case safety reports of ADR, Vigiaccess (video abstract), was used to identify cases of ADR complicating HAE-C1-INH LTP. All cases in VigiBase are self-reported according to MedDRA terms; additional clinical data regarding diagnostic criteria and toxicity management are not reported. Each anonymous report could contain more than one ADR.

Data were collected on 28^th October 2024.

Only adverse reactions with an incidence greater than 3% in at least one of the two drugs were considered. The relative incidence of ADR for the two drugs was analyzed.

Fisher’s test was used to determine if a statistical difference could be found in the relative incidence of the ADR; a p-value of < 0.05 was considered statistically significant.

460 reports were recorded for berotralstat and 3020 for lanadelumab.

Female patients were predominantly represented for both drugs, with a notably higher prevalence observed in the lanadelumab group (Table 1).

Berotralstat was more often associated with adverse gastrointestinal reactions. General disorders (fatigue), administration site reactions, immunological disorders, infections, metabolism, and musculoskeletal and connective tissue disorders were often reported for lanadelumab (Table 2).

Our results confirm the literature’s data reporting prevalent adverse gastrointestinal effects of berotralstat and site reactions and infections of lanadelumab. Notably, patients using lanadelumab more often reported immune system, musculoskeletal, and metabolism disorders.