When it comes to lung diseases, asthma, COPD*, and cystic fibrosis might come to mind. One that may be less familiar is bronchiectasis**, however, just over half a million people in the US will be living with this long-term disease by 2031, according to GlobalData. Like cystic fibrosis and asthma, there is no cure for bronchiectasis, however, unlike its peers, bronchiectasis has seen a severe lack of investment—and there is a distinct lack of disease-modifying drugs available to patients. However, GlobalData believes this is set to change. The leading data and analytics company has identified a recent boost in interest by drug developers and predicts that great strides will be made towards better disease management over the next decade.

Bronchiectasis is characterised by damage to the bronchi air passage that causes abnormal dilation and scarring. The airway becomes inflamed with thick mucus, which is difficult to clear and creates an environment prime for bacterial growth and patients can experience frequent lung infections. Research by the GlobalData Epidemiology team, as part of its ‘Bronchiectasis Market Size and Trend Report’, has assessed the bronchiectasis drug pipeline and collected the opinions of a number of key opinion leaders*** (KOLs) to identify three drugs that are leading the charge: Fasenra, brensocatib, and icenticaftor.

Ramla Salad, Pharma Analyst at GlobalData, comments: “There is a clear need for more targeted therapies that limit and control this burdensome disease. The current treatment options—antibiotics to treat infection, bronchodilators to alleviate chest tightness, and mucolytics to reduce the thickness of phlegm—are simply treating the symptoms of the disease and not addressing the underlying causes. Opportunity remains for developers to continue to conduct clinical research in this area, with the hopes of drugs with a wider variety of mechanism of action (MOA) to enter the space in the future.”

The first drug of interest, Fasenra (benralizumab), is an interleukin (IL)-5α receptor antagonist indicated for the treatment of severe eosinophilic asthma. The drug is currently being investigated in the Phase III MAHALE trial (NCT05006573). Although this trial’s results are not expected to be made public until June 2024, data from other respiratory trials such as COPD and eosinophilic asthma suggests that Fasenra may be efficacious in patients whose presentation of bronchiectasis is eosinophilic.

Salad continues: “KOLs interviewed by GlobalData mentioned that Fasenra will bring relief to patients with eosinophilic presentations of bronchiectasis but other conclusions cannot be made as safety and efficacy data has yet to be released.”

Another promising Phase III agent is brensocatib, an oral selective and reversible dipeptidyl peptidase 1 (DPP-1) inhibitor. It is being investigated in the Phase III ASPEN trial (NCT04594369), which is expected to announce its results in March 2024, however, Phase II data already suggests that this agent has a good safety and efficacy profile.

Salad adds: “KOLs interviewed by GlobalData anticipate that brensocatib may be a gamechanger in the bronchiectasis space due to its unique profile. It is expected to be used in a larger group of patients.”

Finally, Novartis is developing icenticaftor (QBW251), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. The drug is currently being investigated in a Phase IIb trial (NCT04396366) assessing its safety, tolerability, pharmacokinetics, and pharmacodynamics.

Salad notes: “CFTR modulators are widely used in the treatment of cystic fibrosis, which is characterized by homozygous mutations in the CFTR genes. CFTR modulators work by binding to the defective CFTR protein, improving its function, and, in turn, reducing the build-up of thick mucus.

“There is a strong overlap between the pathophysiology of CF and bronchiectasis. In fact, some patients with bronchiectasis have a heterozygous mutation for the CFTR mutation. Although KOLs interviewed by GlobalData mentioned that this offers a promising MOA, it is unknown if icenticaftor will be effective in bronchiectasis patients that do not have these CFTR mutations or mucociliary clearance issues.”

* Chronic obstructive pulmonary disease
** Also known as non-CF bronchiectasis
*** GlobalData’s key opinion leaders include two US and three EU KOLs