Press Release

World-first clinical trial raises hopes of new drug for chronic lung disease

Published on 25 June 2020

A drug which reduces the risk of people living with a chronic lung disease from needing antibiotics or emergency hospital treatment could soon be a reality, according to the results of a clinical trial.

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A drug which reduces the risk of people living with a chronic lung disease from needing antibiotics or emergency hospital treatment could soon be a reality, according to the results of a clinical trial.

The final results from the Phase 2 WILLOW study were announced today by James Chalmers, British Lung Foundation Professor of Respiratory Research at the University of Dundee, at a virtual meeting of the American Thoracic Society broadcast around the world.

Scientists at the University, in collaboration with the global biopharmaceutical company Insmed Incorporated, tested brensocatib in patients living with non-cystic fibrosis bronchiectasis, a long-term lung condition which causes abnormal widening of the airways. The final results demonstrated that patients on brensocatib could potentially reduce their risk of pulmonary exacerbations by more than one-third compared to placebo.

A further clinical trial, also led by the University’s School of Medicine, is currently exploring whether brensocatib can be used to prevent the need for mechanical ventilation in Covid-19 cases.

Bronchiectasis causes a build-up of excess mucus that can make the lungs more vulnerable to infection. Complications associated with the disease, known as pulmonary exacerbations, often require emergency medical treatment. Treatment for bronchiectasis is currently limited to controlling chest infection symptoms using antibiotics.

The drug will need to undergo further rounds of clinical trials and receive regulatory approval before it can be routinely prescribed by doctors, but the scientists have hailed these results as evidence that drugs can potentially be used to treat bronchiectasis directly.

“Living with bronchiectasis means that you’re constantly at risk of needing emergency treatment when the condition worsens,” said Professor Chalmers.

“We currently rely on antibiotics to treat the chest infections caused by bronchiectasis, with few options to stop the disease from getting worse in the first place. We are excited by the possibility of a drug which can break the vicious cycle of inflammation, lung damage, and infection for these patients, giving them a much better quality of life. This trial is a world first in treating an incurable lung condition that affects millions of people worldwide.”

People with bronchiectasis have frequent pulmonary exacerbations, which are normally treated with a short course of antibiotics. In the most serious cases, hospital treatment is required. Symptoms include chronic cough, excessive sputum production, shortness of breath, and repeated chest infections, which can worsen the underlying condition. The disorder affects more than 200,000 people in the UK and accounts for more than 1,500 deaths in this country annually.

Brensocatib is an oral inhibitor of dipeptidyl peptidase I (DPP1), an enzyme responsible for activating neutrophil serine proteases (NSPs), in the most common type of white blood cell. These cells play an essential role in pathogen destruction and inflammatory mediation but, in chronic inflammatory lung diseases, they accumulate in the airways and result in lung destruction and inflammation.

The team behind the study believe brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis, by inhibiting DPP1 and its activation of NSPs.

“We were thrilled to share positive final results from the Phase 2 study of brensocatib at the American Thoracic Society virtual meeting,” said Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed.  “These findings are very meaningful for patients with bronchiectasis, who currently suffer from severe outcomes in the absence of an approved therapy.”

"Importantly, new data presented today demonstrate the relationship between neutrophil elastase reduction and the risk of exacerbation, and serve as further proof of concept of the potential of brensocatib and its unique mechanism of action. We look forward to initiating our Phase 3 program in bronchiectasis in the second half of this year, while also exploring the potential of brensocatib in other neutrophil-driven inflammatory conditions.”

Notes to editors

About the WILLOW study:

WILLOW was a randomised, double-blind, placebo-controlled, parallel-group, multi-centre, multi-national, Phase 2 study to assess the efficacy, safety and tolerability, and pharmacokinetics of brensocatib (formerly INS1007) administered once daily for 24 weeks in patients with non-cystic fibrosis bronchiectasis (NCFBE).

WILLOW was conducted at 116 sites and enrolled 256 adult patients diagnosed with NCFBE who had at least two documented pulmonary exacerbations in the 12 months prior to screening. Patients were randomised 1:1:1 to receive either 10 mg or 25 mg of brensocatib or matching placebo. The primary efficacy endpoint was the time to first pulmonary exacerbation over the 24-week treatment period in the brensocatib arms compared to the placebo arm.

About Insmed:

Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product, ARIKAYCE® (amikacin liposome inhalation suspension), is the first and only therapy approved in the United States for the treatment of refractory Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. MAC lung disease is a chronic, debilitating condition that can cause severe and permanent lung damage. Insmed's earlier-stage clinical pipeline includes brensocatib, a novel oral reversible inhibitor of dipeptidyl peptidase 1 with therapeutic potential in non-cystic fibrosis bronchiectasis and other inflammatory diseases, and treprostinil palmitil, an inhaled formulation of a treprostinil prodrug that may offer a differentiated product profile for rare pulmonary disorders, including pulmonary arterial hypertension. For more information, visit www.insmed.com.

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Grant Hill

Press Officer

+44 (0)1382 384768

G.Hill@dundee.ac.uk

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