A Chronic Cough Pipeline in a Product: Haduvio™
Haduvio™ (oral nalbuphine ER) is a centrally and peripherally acting investigational therapy which we are currently developing for the treatment of serious chronic cough conditions including IPF, interstitial lung diseases, and refractory chronic cough.
“My cough was really so deep that it felt like I broke my ribs, and my ribs became so cramped that I couldn’t even twist [my body].”
Voice of the Patient Report: “Idiopathic Pulmonary Fibrosis”, March 2015.
Chronic Cough in Patients with Idiopathic Pulmonary Fibrosis (IPF)
IPF is a rare, chronic, progressive lung disease, characterized by scarring and thickening of lung tissue. Most patients diagnosed with IPF suffer from a dry, non-productive chronic cough that interrupts their daily living and significantly contributes to poor quality of life.
What is chronic cough in IPF?
IPF is a serious, end-of-life disease. Chronic cough is one of the most common symptoms of IPF and has a significant impact on quality of life in these patients. There are estimated to be 140,000 IPF patients in the US and more than 1 million patients ex-US, where up to 85% of these patients experience chronic cough. There are no approved therapies for the treatment of chronic cough in IPF and the cough often isn’t affected by antitussive therapy. Patients with chronic cough in IPF can cough up to 1,500 times per day, leading to increased feelings of fear and stress as it causes shortness of breath. Coughing spells or episodes lead to significant fatigue, an urge to breathe, low levels of oxygen in blood, and some patients also experience loss of bladder control. The social impact of chronic cough in IPF is increased because of limited exercise ability, reduced walking distance, and the need to use additional oxygen. The chronic cough in IPF may be an early clinical marker of disease activity that could potentially help to identify patients at high risk of progression and predict time to death or lung transplant. In addition, the chronic cough in IPF may also contribute to enhanced activation of profibrotic mechanisms and disease worsening.
Refractory Chronic Cough (RCC)
Refractory chronic cough is defined as a constant cough lasting ≥8 weeks that doesn’t respond to the standard-of-care treatment for cough, even after the initial condition which triggered the cough is treated.
What is RCC?
Refractory chronic cough is defined as a constant cough lasting ≥8 weeks that doesn’t respond to the standard-of-care treatment for cough. It is estimated that ~5-10% of adults worldwide suffer from chronic cough. RCC patients can experience more than 700 coughs in a day with 96% of patients reporting the cough affects their quality of life. Not only does it affect the patients themselves but 94% of chronic cough patients reported that cough worried or disturbed their family and friends.
There is usually a lengthy diagnosis period where physicians explore treating underlying disease conditions (asthma, gastroesophageal reflux, upper airway cough syndrome, eosinophilic bronchitis, etc.). When they do not have success in controlling chronic cough, they move forward with a diagnosis of RCC. This delay in identifying RCC, along with added investigation and ineffective treatments, can increase the patients’ burden.
Chronic Cough in Interstitial Lung Diseases (ILDs)
ILDs are highly burdensome diseases. Specifically, patients with chronic fibrosing (scarring) ILDs, which have a risk of developing a progressive phenotype (which worsens the sickness no matter the treatment course) are known to suffer from chronic cough. Examples of chronic fibrosing ILDs include IPF, hypersensitivity pneumonitis, non-IPF idiopathic interstitial pneumonias, autoimmune ILDs, exposure-related, and sarcoidosis.
What is chronic cough in ILDs?
There are many kinds of ILDs. Patients with ILDs that are likely to experience progressive fibrosis (where the lungs continue to scar) are more likely to experience chronic cough, with 94% of these patients reporting cough. The most common type of progressive fibrosis ILD (PF-ILD) is IPF. However, progressive ILDs also include hypersensitivity pneumonitis, non-IPF idiopathic interstitial pneumonias, autoimmune ILDs, exposure-related, sarcoidosis, and other ILDs. Much like chronic cough in IPF, ILD patients can experience a high frequency of coughing with the mid-point ranging between 200-500 coughs per day. This coughing is not productive (does not remove mucus from the lungs) and does not relieve the patients’ urge to cough. This can result in patients feeling nervous, tired, and often times they remove themselves from situations that might bring on a coughing fit (walking, talking, laughing).
Research in ILD patients found that a lower Leicester Cough Questionnaire score (based on patients’ answers to questions about how cough affects their lives) meant patients had a lower cough-specific quality of life and corresponded with an increase in risk of respiratory-related hospitalization, death, and lung transplant.
There are currently no approved therapies for chronic cough in ILDs.