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Drug trial aims to treat severe outcome of COVID-19

The University of Dundee is leading a major new clinical trial of a drug it is hoped may help to prevent the worst ravages of COVID-19.

Researchers from the University’s School of Medicine are partnering with global biopharmaceutical company Insmed Incorporated to conduct trials of brensocatib (formerly known as INS1007), a drug being developed to treat lung inflammation, in COVID-19 patients.

While COVID-19 results in a mild infection in most people, up to 20% of patients develop inflammation of the lungs which can require them to be ventilated. Though COVID-19 is caused by a viral infection, research has shown that the body’s own inflammatory response, designed to clear the virus, causes the lung damage that ultimately leads to respiratory failure and death in severe cases.

Insmed will provide funding and clinical drug supply for the STOP-COVID19 (Superiority Trial of Protease inhibition in COVID-19) trial. The Dundee researchers will explore whether brensocatib can reduce the incidence of acute lung injury and prevent mechanical ventilation. It is hoped that the treatment will also lead to patients spending fewer days dependent on oxygen and shorter periods of time in hospital, reducing the burden on healthcare systems.

STOP-COVID19 is one of a number of studies into the disease to have been given urgent public health research status by the Department of Health and Social Care. It is also the first Scottish-led drug trial in COVID-19 to take place.

Trials conducted to date have shown that brensocatib reduces inflammation in the lungs of people with underlying lung conditions and it is hoped that it will have a similarly beneficial effect in those suffering from COVID-19.

STOP-COVID19 will recruit 300 volunteers from 10 hospitals across the UK, with patients offered the chance to participate immediately after their diagnosis. Half the group will receive brensocatib in addition to standard hospital care while the other half will receive a placebo. The study is expected to begin enrolment at the start of May.

The trial is being led by James Chalmers, British Lung Foundation Professor of Respiratory Research at the University. Professor Chalmers is also Consultant Respiratory Physician at Ninewells Hospital, one of the trial sites.

He said, “High rates of patients requiring ventilation and overwhelming intensive care unit capacity has been a major cause of excess deaths around the world and we hope that brensocatib can put a brake on the devastation this disease causes, to literally stop COVID-19 when it begins attacking the lungs.

“The medical community has never faced a more urgent need for treatment than the unprecedented situation we face today with COVID-19. Our researchers at the University of Dundee have been studying this kind of lung inflammation for more than 10 years and so are in the perfect position to rapidly intervene in patients to try to prevent the worst outcomes of COVID-19.”

Brensocatib is a novel oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) currently being developed by Insmed for the treatment of bronchiectasis and other inflammatory diseases. DPP1 is an enzyme that catalyzes the activation of neutrophil serine proteases (NSPs) in neutrophils when they are formed in the bone marrow.

Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. By inhibiting the activation of NSPs, brensocatib may offer applicability in a range of neutrophil-mediated diseases. Neutrophil influx into the lungs is a defining characteristic of acute respiratory distress syndrome (ARDS), a severe outcome of COVID-19 that is associated with high mortality. Reduction of neutrophil proteases may reduce the progression of lung injury and the need for ventilation in these patients.

In the recent Phase 2 WILLOW study in adult patients with non-cystic fibrosis bronchiectasis, brensocatib met its primary and a key secondary endpoint and demonstrated that its anti-inflammatory approach has the potential to treat the debilitating cycle of inflammation, infection, and lung damage.

Professor Chalmers continued, “The mechanism of action of brensocatib observed in a study in bronchiectasis patients provides a strong rationale for evaluating this novel treatment candidate in other neutrophil-driven inflammatory conditions. It is my hope that it will have applicability in patients at risk of ARDS—a devastating outcome of COVID-19 for which there are currently no approved therapies.”

Martina Flammer, M.D., Chief Medical Officer of Insmed, said, “The global COVID-19 pandemic has generated an extraordinary response from the biopharmaceutical industry to bring to bear all potential means of fighting this disease and preventing its most severe outcomes, including the need for ventilation and ICU stays.

“At the start of the outbreak, Insmed began pursuing an in vivo mouse model to better understand the potential of brensocatib in preventing ARDS. As we rapidly advance this early-stage research simultaneously, we are very pleased to support Professor James Chalmers and the University of Dundee in leading a controlled clinical trial that will help us evaluate the potential impact of brensocatib on hospitalised patients suffering from severe COVID-19.”

Study investigator and NHS Tayside R+D director Professor Jacob George added, “This is the first Scottish-led drug trial into COVID-19 and it has been prioritised and designated as an urgent public health study. Tayside can be justifiably proud of this and we look forward to collaborating with other NHS Boards in Scotland to recruit eligible patients onto the trial.”

More information about studies that have been given urgent public health status and the single, national prioritisation process that has been established to prevent duplication of effort and to ensure that the resources and capacity of the health and care system to support COVID-19 research are not exceeded is available at https://www.nihr.ac.uk/covid-19/.

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