The world’s first phase three trials of a new drug have shown that it can ease the often-distressing symptom of chronic cough with few side effects.
Alyn Morice, Professor of Respiratory Medicine at Hull York Medical School, University of Hull, and Head of the Hull Cough Clinic at Hull University Teaching Hospitals NHS Trust, who has spent over 30 years treating patients with chronic cough, believes the drug will have a dramatic impact on patients. He said: “Chronic cough is extremely debilitating for individuals. Those suffering with the condition get very sensitive nerves in their throat and their coughing is triggered by changes in temperature, perfumes and aerosols. They will also experience horrible paroxysms of coughing.
“ As a result, they are unable to do everyday activities such as going to the theatre or to church. The COVID-19 pandemic has been particularly hard for patients, with some experiencing verbal and physical abuse for coughing out loud in public.”
The two Phase 3, randomised, double blind 52-week trials recruited 2,044 participants in 17 countries. It involved an international collaboration between academics, including Jacky Smith, Professor of Respiratory Medicine at The University of Manchester and Honorary Consultant at Wythenshawe Hospital, Manchester University Foundation Trust and Director of NIHR Manchester Clinical Research Facility (CRF).
The drug is being developed in collaboration with the pharmaceutical company MSD, who funded the trials.
In the Cough 1 trial, 730 participants were given either Gefapixant 45mg, 15 mg or a placebo and in the Cough 2 trial, 1,314 participants in the were given either Gefapixant 45 mg, 15mg or a placebo.
The study, which has been published in The Lancet, shows that Gefapixant 45 mg demonstrated an 18.5% reduction in 24-hour cough frequency relative to placebo in COUGH-1 and a 14·6% reduction in COUGH-2.
Both studies demonstrated the efficacy of gefapixant and the durability of its effects on cough frequency reduction up to 6 months with gefapixant 45 mg. The 15mg dose did not demonstrate a significant reduction in cough frequency versus placebo.
Over 52 weeks, some patients experienced mild or moderate taste disturbances in the gefapixant 45 mg group which reversed while on the treatment or after discontinuation. More serious side effects were rare.
Chronic coughing - defined as a cough lasting over 8 weeks – is thought to affect between 4% and 10% of the population, some of whom cough thousands a time a day over many years.
While some patients improve with treatment of associated conditions such as asthma and reflux disease, many do not.
The condition can cause abdominal pain, urinary incontinence in women, as well as anxiety, depression and difficulty sleeping.
Professor Morice said: “These large clinical trials from around the world have confirmed the efficacy and safety of the medicine and our patients are anxiously waiting for it to be prescribed for what is a poorly recognised but very distressing condition.
“There has been no drug developed for the treatment of cough for over 50 years and this can be regarded as a breakthrough since it specifically attacks the irritation leading to the tickle in the throat which precipitates the cough.”
Professor Smith said: “Billions of pounds are spent annually on over-the-counter cough and cold medicines despite a lack of evidence to support their efficacy, concerns about the potential for abuse and risk of harm in overdose.”
The study monitored the impact of Gefapixant – which can target P2X3receptors in the nerves that control the excessive coughing – using a special cough monitoring system originally developed in Manchester to counts coughs.
The drug was initially developed as a pain killer, until the researchers discovered it had a significant impact on chronic cough.
Some existing drugs have also been shown to improve chronic cough, but their use is often limited by unpleasant side effects.
It is thought a chemical called adenosine triphosphate (ATP), released as a response to inflammation in airways, is an important mechanism for patients with chronic cough. Gefapixant blocks the ATP receptor on the sensory nerves.
Professor Morice added: “Whilst this drug does not work in all patients, during the clinical trials we saw dramatic effects with the cough effectively cured even if the patient had been coughing for over 20 years.”
Two thirds of patients with this previously intractable condition and who had been coughing for an average of 10 years gained a relief of their cough in the trial.
Retired publican Lorraine Falcon has been coughing continuously for 27 years.
She said: “Thank you all. I have had this chronic cough for over 20 years, it has at times spoilt my life, Christmas, birthdays et cetera. It is 24/7 every single day of every single year.
“The comments from other people, the worry in the first 5 years and particularly during Covid has been dreadful. You feel like a leper.
“Nothing has really helped me until now. The best thing in 20 years, your tablet is a miracle for me.”