Bronchiectasis: Pipeline Review, 2024

Bronchiectasis, refers to an uncommon chronic lung disease, wherein the walls of the bronchi (airways) are widened and thickened from infection and inflammation. It is understood that the early diagnosis and treatment of this disease is of paramount importance to prevent further damage to the lungs. Some of the symptoms indicative of bronchiectasis are coughs with significant amounts of mucus and pus, dyspnea, wheezing, persistent colds, and hemoptysis. The healthcare providers generally categorize the type of bronchiectasis, on the basis of the damage to the bronchi/airways, into:

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  • Cylindrical (Tubular)
  
  
  • Varicose
  
  
  • Cystic
  
  
  
  

Epidemiology:

Bronchiectasis is generally caused by the presence of autoimmune diseases such as celiac disease, immunodeficiency disorders such as HIV or diabetes, chronic obstructive pulmonary disease (COPD), and alpha-1 antitrypsin deficiency, and other diseases. Also, bronchiectasis is caused by recurring infections that can cause damage to the airway walls such as tuberculosis, whooping cough, pertussis, and other diseases.

According to the data published by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in July 2024, the global prevalence of bronchiectasis is estimated to be 1 million individuals, with the U.S. accounting as one of the key countries with a substantial patient burden of 400,000 individuals. Some of the other countries with a substantial burden of bronchiectasis includes the U.K., and Germany. According to a study published by the Lancet in August 2023, the prevalence of bronchiectasis has increased globally in the past two decades.

Therapeutic Assessment:

The gold standard for the diagnosis of bronchiectasis, according to the National Health Service (NHS) of the U.K., is conducting a high-resolution CT (HRCT) scan as it captures a very detailed image of the inside of the body, with the bronchi/airways being outlined very clearly and precisely. The administration of the antibiotics for the treatment of bronchiectasis is considered to be the mainstay of treatment for more than the past 4 decades. After the assessment of the clinical situation of the patient, parenteral, oral or aerosolized antibiotics are administered. Despite the significant patient burden associated with the disease, there have no marketing approvals by regulatory agencies till date for this condition. Most of the drugs are used off-label for the management of this condition.

Key Products:

Some of the acceptable choices of antibiotics for the outpatients who are mildly to moderately ill, are trimethoprim-sulfamethoxazole, amoxicillin, tetracycline, macrolides (such as azithromycin or clarithromycin), second generation of cephalosporin, or fluoroquinolones. For patients, who are considered to be moderately to severely ill, parenteral antibiotics such as aminoglycoside (gentamicin, tobramycin), antipseudomonal synthetic penicillin, a third-generation cephalosporin, or a fluoroquinolone will be administered. In recent times, aerosolized antibiotics are also being administered.

Major Players in Bronchiectasis:

For bronchiectasis, as of now, there are no major approved drugs. Hence, there is a big gap that can be filled in by potential competitors. However, for now, some of the major players for bronchiectasis, are the key players in the antibiotics market such as Pfizer Inc, Abbott, and GSK plc.

Bronchiectasis Treatment Market Overview:

The bronchiectasis treatment market has a considerably potential for growth as the market is completely untapped, in terms of approvals and launches of effective therapeutics. Furthermore, even in the developed markets such as the U.S., Europe, and Japan, there has been a distinct lack of regulatory approvals. Also, certain market drivers such as the high prevalence of the disease, unmet patient need, and favorable clinical trial results will boost the growth potential of the market. Hence, several potential competitors are eyeing this market to become the first ever company with a regulatory approval for bronchiectasis.

Pipeline Analysis: 

Overview of the Pipeline:

In terms of the distribution of the pipeline candidates by the phase of the clinical development, an overwhelming proportion of pipeline candidates, more than 75% belong to the phases 1, 2, and 3.

Pipeline By Mechanism of Action:

Till recently, there had been a stagnancy in the bronchiectasis treatment market, as a substantial number of clinical trials yielded, no positive results that could lead to the first regulatory approval in the market. However, in June 2020, positive results from the Phase 2 WILLOW Study of Brensocatib for patients suffering from non-cystic fibrosis bronchiectasis was unveiled. This has since spurred an increased influx of pipeline candidates with novel mechanisms of actions:

• Reversible Inhibitor of Dipeptidyl Peptidase 1 (DPP1): The drugs with this mechanism of action, such as Insmed Incorporated’s brensocatib substantially reduces the frequency and risk of bronchiectasis exacerbations at 24 weeks through the inhibition of dipeptidyl peptidase I and the decline in the activation of the neutrophil serine proteases.


• Alpha 1-Proteinase Inhibition: In terms of drugs with the novel mechanism of actions, another subset of drugs are those which are used as an augmentation therapy are the human alpha-1-proteinase inhibitors. Several studies have indicated that alpha-1-proteinase inhibitors significantly declines the exacerbation frequency and improves the clinical conditions for the patients with bronchiectasis and a deficiency of alpha-1-antitrypsin deficiency.

Pipeline By Route of Administration:

One of the key pipeline candidates that leads the market in terms of its progress in the clinical trials’ is Insmed Incorporated’s drug candidate of brensocatib, which is administered through the oral route of administration. Hence, there is a positive representation of the pipeline drug candidates that are administered orally. 

Pipeline By Molecule Type:

A significant number of players engaged in the clinical trials for bronchiectasis are emphasizing on the development of small molecules such as Insmed Incorporated, Boehringer Ingelheim International GmbH. Only a limited number of players such as Armata Pharmaceuticals, Inc., and CSL Behring are engaged in the development of biologics for the treatment of bronchiectasis.

Pipeline, By Company:

Certain main players engaged in the clinical trials for bronchiectasis are Insmed Incorporated, Boehringer Ingelheim International GmbH, Armata Pharmaceuticals, Inc., CSL Behring, CHIESI Farmaceutici S.p.A., and other prominent companies.

Clinical Trial Insights:

Ongoing Clinical Trials: Some of the key pipeline candidates under clinical trials are as follows:

Phase 1:

• CSL787: CSL Behring


• BI 1323495: Boehringer Ingelheim International GmbH

Phase 2:

• AP-PA02: Armata Pharmaceuticals, Inc.


• CHF6333: CHIESI Farmaceutici S.p.A.


• BI 1291583: Boehringer Ingelheim International GmbH


• HSK31858: Haisco Pharmaceutical Group Co., Ltd.

Phase 3:

• Brensocatib: Insmed Incorporated
  
  
  
  • Study Description: The ASPEN (Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis) study is being conducted to evaluate the efficacy of brensocatib at 10 mg and 25 mg, in comparison to placebo. This will be tested on the rate of pulmonary exacerbations (PEs) over the time duration of 52 weeks. This study is being conducted across the globe, with the study type being interventional. The primary purpose of the clinical trial is treatment, with the allocation being randomized. The interventional model of the study is parallel assignment and the masking is double.
  
  
  
  


• CMS: ZAMBON COMPANY S.P.A.


• RHB-204: RedHill Biopharma Ltd.

Future Trial Prospects:

• June 2024: The research teams at Freeman Hospital became the first in the world to recruit a patient for a clinical trial for bronchiectasis, which is sponsored by Sanofi.


• April 2023: Insmed Incorporated announced the closure of the adult patient enrolment for the ASPEN clinical trial of brensocatib. The company is currently conducting the clinical trials for the ASPEN study in over 460 sites across 40 countries worldwide. While the enrolment for the adults’ patients is currently closed, the company is currently undertaking the recruitment of adolescent patients aged 12 to less than 18 years.

Regulatory Landscape:

• FDA and EMA Approvals: No drug till date have been approved for bronchiectasis, by either the U.S. FDA or the European Medicines Agency due to the absence of compelling clinical evidence for approvals. However, in recent times, there have demonstrations of positive patient outcomes in several landmark clinical trials, that may pave the way for a drug to be potentially approved.


• Orphan Drug Designations: According to the data published by Boehringer Ingelheim International GmbH, bronchiectasis was initially considered an orphan disease. However, increased awareness and improvement in clinical diagnostics led to significantly higher prevalence rates for this disease. Hence, it is no longer considered an orphan disease and has no orphan drug designations for it.


• Market Authorization Challenges: Some of the reasons that have caused hindrances to the players planning to launch drugs for bronchiectasis is the progression of the disease. The disease is considered to be irreversible and the current guidelines for treatment are based on limited clinical evidence. Furthermore, the lack of large, randomized trials and issues such as problems in candidate recruitment for clinical trials have caused several studies to fail. All these parameters have led to a lack of regulatory approval by any of the major agencies. 

Report Scope

• A thorough assessment of the pipeline products by areas such as development stage; route of administration; drug class; indication; sponsor; molecule type and drug target


• Comprehensive profiles of the pipeline products with details such as company overview; product description; R&D status; development activities; mechanism of action; molecule type; development stage; indications; funding and route of administration


• Overview of dormant and discontinued pipeline products


• Key insights about the epidemiology of conditions being treated by the pipeline products and overview of the addressable or current market for the pipeline products


• Overview of the latest developments; news articles, press releases, and relevant conferences

Report Methodology

• All pipeline reports are built through the analysis of data primarily collected through credible desk research sources. Secondary research is supplemented by interviews conducted with key opinion leaders.


• Desk research sources include global and regional clinical trials databases; annual reports, websites, press releases & investor presentations of companies; white papers; news articles; reports published by industry associations; articles/reports published on databases such as NCBI, ResearchGate; internal databases

Reasons to Buy this Report

• Develop effective growth strategies based on a comprehensive overview of the R&D activity and pipeline products for bronchiectasis


• Identify emerging players or competition in the market based on pipeline products and develop strategies to counter the emergence of these players


• Identify the focus of leading players about R&D for bronchiectasis


• Identify potential companies from a partnership or acquisition point of view based on current synergy in R&D activities or strategies to diversify R&D focus to drive growth in business


• Analyze the reasons behind dormant and discontinued products to make changes in the R&D focus if necessary