ORLADEYO™ (berotralstat) is the first and only oral therapy indicated for the treatment of hereditary angioedema (HAE) in adults and paediatric patients aged 12 years and older.
It is available as a hard gelatine oral capsule with a white opaque body for 150mg dosage strength, as well as light blue opaque body for 110mg dosage strength.
Patients and healthcare professionals will receive the drug through a single point of contact via EMPOWER Patient Services, which will receive the drug through Optime Care, an exclusive speciality pharmacy provider for ORLADEYO.
Developed by BioCryst Pharmaceuticals, ORLADEYO (BCX7353) received fast track designation from the US Food and Drug Administration (FDA) in August 2018.
In November 2019, BioCryst partnered with Torii Pharmaceutical for the commercialisation of BCX7353 in Japan.
The company submitted a new drug application (NDA) for the drug to the FDA in December 2019 and received approval in December 2020. The drug also gained orphan drug status in the European Union (EU) and Sakigake designation in Japan. ORLADEYO is currently under regulatory review in Japan and the EU.
Hereditary angioedema (HAE) is a rare, genetic and potentially life-threatening condition caused by the deficiency of a C1 esterase inhibitor (C1-INH) enzyme.
C1-INH inhibits plasma kallikrein whose activation due to reduced levels of C1-INH is responsible for the angioedema attacks.
HAE affects one in 10,000 to one in 50,000 individuals. Patients with HAE often experience several attacks per month when left untreated, and the swelling from each attack lasts for three days or longer.
The current standard of treatment for patients with HAE includes repeated infusions or injections of plasma-derived C1-INH to avoid swelling attacks, as well as injection therapy to control attacks when they occur.
Common symptoms include angioedema, abdominal pain, ascites, facial oedema and intestinal oedema.
Berotralstat binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to produce cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that enhances vascular permeability, causing HAE-associated swelling and pain.
In patients with HAE, C1-inhibitor (C1-INH) deficiency or dysfunction result in unregulated production of plasma kallikrein naturally, which contributes to an unregulated increase in plasma kallikrein activity, leading to angioedema attacks.
Berotralstat lowers plasma kallikrein production to regulate excess bradykinin generation in HAE patients.
FDA approval of ORLADEYO was based on the randomised, multi-centre, placebo-controlled, double-blind, parallel-group clinical study (Trial 1).
The study involved 120 patients who suffered at least two confirmed attacks during the first eight weeks of the run-in duration and received at least one dose of study drug.
Patients were randomised in 1:1:1 ratio to receive berotralstat 110mg, 150mg or placebo orally once daily with food during the 24-week treatment duration.
Other prophylactic HAE medicines used by the patients were discontinued before entering the study, however, the use of rescue drugs for the treatment of severe HAE attacks were allowed.
Reduction in the HAE attack rate in the intent-to-treat (ITT) population was the primary endpoint of the study.
ORLADEYO 150mg and 110mg dosages achieved statistically significant reductions in the frequency of HAE attacks versus placebo for the ITT population.
Reductions in attack rates were observed during the first month of treatment with ORLADEYO 150mg and 110mg and were continued over 24 weeks. The percentage reduction in the HAE attack rate was higher with ORLADEYO (150mg and 110mg) compared to placebo, regardless of the attack rate during the run-in period.
Approximately 58% of patients receiving 150mg ORLADEYO and 51% of patients receiving 110mg ORLADEYO showed equal to or more than 50% reduction in the HAE attacks compared to baseline.
The rate of mild to severe attacks decreased by 40% and 10% in patients receiving 150mg ORLADEYO and 110mg ORLADEYO, respectively, compared to placebo.
Common side-effects of ORLADEYO reported in patients during the trial include abdominal pain, vomiting, diarrhoea, back pain and heartburn.
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