EMA has recommended granting a marketing authorisation in the European Union (EU) for Brinsupri (brensocatib) 25 mg tablets, for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in patients aged 12 years and older who have had two or more exacerbations (flare-ups) in the prior 12 months.
NCFB is a chronic, progressive lung disease resulting in damaged airways and severe pulmonary dysfunction, often leading to chronic cough and airflow obstruction due to abnormal mucus production. It is driven by repeated infections and inflammation, and can be triggered by several causes, including respiratory infections, autoimmune diseases (when the body’s own defence system attacks normal tissue) and immunodeficiency disorders (when body defences are reduced from birth). The estimated number of patients with NCFB in the EU is between 400,000 and three million.
Patients typically experience between one and four exacerbations per year. Exacerbations are associated with a progressive decline in lung function, decreased quality of life and increased mortality. There are currently no authorised medicines for NCFB; patients rely on airway clearance and receive antibiotics and anti-inflammatory medicines.
The active substance of Brinsupri is brensocatib, a substance that inhibits dipeptidyl peptidase 1 (DPP1), an enzyme involved in the activation of neutrophils (a type of white blood cells). Recurrent activation of neutrophils in patients with NCFB leads to the excessive release of the proteins neutrophil serine proteases (NSPs), causing airway wall damage, excessive mucus, sustained inflammation and impaired functioning of the immune system. By inhibiting DPP1, brensocatib prevents the activation of NSPs, thereby reducing their harmful activity in the lungs.
Brinsupri was supported through EMA’s PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients’ unmet medical needs. EMA’s human medicines committee, the CHMP, reviewed the application for marketing authorisation under an accelerated timetable because Brinsupri is considered to be of major public health interest.
The recommendation is based on the results of a randomised, double-blind, placebo-controlled clinical trial in 1,767 patients. Patients receiving Brinsupri 25 mg tablets had a 19.4% reduction in the annual rate of pulmonary exacerbations and a 14-week delay in the median time to the first pulmonary exacerbation. The proportion of patients remaining exacerbation-free at week 52 was also significantly higher in those treated with Brinsupri.
The most common side effects reported with Brinsupri were headache, inflammation of the gums (gingival and periodontal diseases), and problems with the skin, including hyperkeratosis (thick skin), dermatitis (swelling and irritation of the skin), rashes and dry skin.
The opinion adopted by the CHMP is an intermediary step on Brinsupri’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
Notes:
- The total randomised population (1,767) includes both the Brinsupri 10 mg and 25 mg treatment groups.
- The applicant for Brinsupri is Insmed Netherlands B.V.
- Brinsupri was granted eligibility to PRIME on 27 February 2020 for the treatment of non-cystic fibrosis bronchiectasis in patients 12 years of age and older with two or more exacerbations in the prior 12 months.
