Hereditary angioedema (HAE) is a
rare disease that causes serious health problem and affects on quality of life for patient due to recurrent episodes of
angioedema in various body such as the skin, larynx, digestive tract, and limbs. Many HAE patients have deficiency or dysfunction of C1 inhibitor, impaired regulation of
plasma kallikrein activity and overproduction of
bradykinin, resulting in leading to episodes of increased capillary hyper permeability and
angioedema.
Therapy of HAE consists of on-demand treatment for acute attack and prophylactic treatment by suppressing the onset of acute attack in the short and long term. However, no
drug has been approved for long-term prophylaxis in Japan.
Berotralstat hydrochloride (ORLADEYO Capsules 150 mg) is an oral, selective
plasma kallikrein inhibitor approved for the suppression of the onset of acute attacks in HAE in Japan in January 2021. Preclinical studies demonstrated that
Berotralstat is a potent and highly specific inhibitor of human
plasma kallikrein activity.
Berotralstat suppressed
bradykinin production in the HUVEC system. Clinical studies demonstrated that
oral administration of
Berotralstat to HAE type I or type II patients at a dose of 150 mg once daily showed a reduction of HAE attack rate and clinically significant change in
angioedema quality of life score. The most common side effect was gastrointestinal symptoms. In conclusion, preclinical and clinical data indicated that
Berotralstat is an effective treatment for long-term prophylactic treatment by suppressing the onset of acute attack in HAE patient and is considered to be a useful treatment option for patients.