A major international study led by clinicians in Southampton has found a drug which can ‘block’ disease-triggering molecules in the lung significantly slows the progression of a fatal condition.
Nintedanib, originally developed as a treatment for lung cancer, has been found to halve the annual decline in breathing capacity normally seen in patients diagnosed with idiopathic pulmonary fibrosis (IPF).
The condition, which is part of a group of disorders known collectively as interstitial lung disease, causes inflammation and scarring of the lung tissue and sufferers have an average life expectancy of between just three and five years.
IPF affects around 15,000 people over 60 in the UK, mainly men and former smokers, and is already responsible for 5,000 deaths and 5,000 new cases every year.
Nintedanib is the first treatment to specifically target key molecules known to cause fibrosis in the lungs of patients with the condition.
It works by blocking the signals sent by enzymes known as tyrosine kinases which, without intervention, go on to activate the disease by creating excess tissue build-up and scarring and, as a result, block the passage of oxygen.
The study, led by Professor Luca Richeldi, who is based at the National Institute for Health Research Southampton Respiratory Biomedical Research Unit, involved 1,066 patients from 205 centres in 24 countries in the Americas, Europe, Asia and Australia.
It compared the lung function of 638 patients who received nintedanib with 423 who received a placebo in two replicate 52-week trials by testing the amount of air participants could expel after their deepest breath, known as forced vital capacity.
In the first study, the decline in breathing capacity of 309 patients who received treatment was cut by more than half (52%), with an average loss of 114.7ml of air compared to 239.9ml among the placebo patients.
The second study saw a similar reduction in decline (45%), with an average loss of 113.6ml of lung capacity in 329 patients on medication compared to 207.3ml among the 219 on placebos.
The average annual reduction in healthy individuals is between 30 to 50ml of air over a year.
In addition, nintedanib delayed the onset of patients' first severe respiratory attack – known as an acute exacerbation – with only 5% of patients suffering at least one event compared to 8% in the placebo group.
Prof Richeldi, a consultant in respiratory medicine at Southampton General Hospital, said the findings, presented at the international conference of the American Thoracic Society in San Diego and published online by the New England Journal of Medicine, would offer patients a “new direction” in treatment.
“The prognosis for patients with IPF is worse than many cancers and cases are increasing by 5,000 a year in the UK alone, so the need for new, targeted and more effective treatments has never been greater,” he said.
“Nintedanib specifically targets some key molecular pathways known to be involved in IPF, which gives us a much clearer insight into how the body works and how we might be able to further develop treatments.”
He added: “The impact of this study cannot be overstated. These are exciting results and mean nintedanib has the potential to offer patients a new direction in treating this aggressive disease.”
Prof Richeldi, who is also chair of interstitial lung disease at the University of Southampton, said it was now “highly likely” the drug would be licensed worldwide within the next year, but may be available to some patients in the near future.
He said: “We expect an advance use programme to begin in Europe before next summer, so the drug may become available to at least some patients within the next few months.”
The study was funded by Boehringer Ingelheim.
Posted on Monday 19 May 2014