Cough! Cough! Every time something goes down the wrong pipe, we cough it out. Within seconds, it gets normal. We catch flu, or cold, cough accompanies for a week or two. However, what if cough decides to befriend the person for a time period more than usual, say, around eight weeks or more? It can be worrisome, and reasons can be many. 

Any cough that persists more than eight weeks is referred to as Chronic refractory cough (CRC). Most often the primary reason behind the manifestation of CRC is associated with some viral infections that affect upper and lower respiratory tracts of the person. However, conditions including asthma, cancer, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pulmonary tuberculosis, and several others are among other identified risk factors contributing to the development of Chronic refractory cough. Furthermore, lifestyle adaptations such as cigarette smoking, obesity, or occupational irritants are also some of the triggering factors of CRC. 

Coughing is so common that it often goes unnoticed and is mostly benign. However, the persistence of chronic cough is the first noticeable sign that signifies respiratory involvement. Other pulmonary signs and symptoms include wheezing, stridor, dyspnea, hoarseness or aphonia, globus, dysphonia, and tenderness over the laryngotracheal cartilage. As per DelveInsight estimates, the total Chronic cough prevalent population in the 7 MM was estimated to be 84,854,266 in 2020; and for Chronic refractory cough, the prevalence was recorded to be  17,600,264 in 2020. Interestingly, several studies show a preponderance of females. The reason behind it still remains unclear; however, this may be related to the increased sensitivity of cough reflex in women. Further, the CRC epidemiological analysis demonstrated an increasing trend in the CRC prevalence in the next coming decade. 

However, the Chronic refractory cough market is dominated by off-label therapies. Currently, the CRC treatment involves the use of various over-the-counter drugs and therapies. However, over time, international guidelines have been developed to help clinicians, and physicians accurately diagnose, assess the severity and treat the condition timely. According to the recent guidelines published by the American College of Chest Physicians (ACCP) four categories of CRC treatment regimen involves the use of nonpharmacologic therapies, inhaled corticosteroids, neuromodulatory therapies, and other therapies. However, DelveInsight’s Chronic refractory cough market is majorly dominated by nonpharmacologic therapies, which include Speech Therapy and Physiotherapy. Then, comes pharmacologic therapies such as Neuromodulators, Proton pump inhibitors, Inhaled Corticosteroids, and other treatment options. Neuromodulators include Opiates (morphine, codeine, tramadol, etc.), gabapentin, pregabalin, morphine, amitriptyline, and baclofen, which act on the heightened neural sensitization that is involved in the pathogenesis of CRC. 

Among the available pharmacologic therapies, Codeine is one of the most commonly used drugs in the CRC treatment market landscape. Morphine, Gabapentin and Tramadol are also among the frequently used therapies to provide relief from a chronic cough. Gabapentin has recently received a recommendation in the American College of Chest Physicians (CHEST) Guideline and Expert Panel Report as a treatment option for chronic cough. Another drug that has proven record in relieving pain associated with Chronic refractory cough is Baclofen. Treatment of chronic cough with Amitriptyline is reported to reduce cough in several studies. Other classes of drugs used to treat CRC include Inhaled corticosteroids, which are effective in eosinophilic airway inflammation. Esomeprazole, a proton pump inhibitor, helps in relieving the acid-reflux in cough associated with Gastro-oesophageal reflux (GOR). Another drug Ipratropium bromide is used as a bronchodilator, which can provide short-term relief from cough. A combination of nonpharmacologic and pharmacologic interventions can do wonders in some CRC cases. Combining speech therapy with drugs to provide relief to the patients can produce better outcomes at a relatively better pace.  

Unfortunately, in many situations, patients continue to experience CRC in spite of following published guidelines for diagnosis and treatment. Further, most of the available over-the-counter drugs have Dextromethorphan, as an active ingredient which is considered to have opiate properties. Thus, with the available therapies, there is always an associated risk of misuse and side effects such as psychiatric symptoms. A lack of approved therapy and biomarkers for accurate diagnosis of Chronic refractory cough also requires serious attention of pharma players and the scientific community. However, there is quite a lot of movement in the landscape in terms of ongoing trials and investigation of novel candidates that are effective, in compliance with the patient’s adherence, and cause minimum side effects.

The expected launch of pipeline therapies such as Orvepitant Maleate, BLU-5937, Gefapixant (MK-7264), BAY1817080 (Eliapixant) and S-600918 may increase market size in the coming years, assisted by an increase in the prevalent population of Chronic Refractory Cough. Owing to the positive outcomes of the upcoming products by key players such as Merck, Nerre Therapeutics, Bayer, Shionogi and Bellus Health, the CRC market will create a significant positive shift in the Chronic refractory cough market size. The market size of CRC in the seven major markets is expected to show a positive growth at a CAGR of 6.57% during the study period 2018–2030. 

Amidst the shine, an inclination towards the use of generics and the fear of trial failure in the late-stage clouds the hopes of the smooth and steady growth of the Chronic refractory cough market size. Nevertheless, a significant anticipated increase in the Chronic refractory cough prevalent population shall drive the market size growth forward. The Chronic refractory cough market has only P2X3 inhibition as a clinically validated treatment approach so far and currently, there are only four emerging therapies targeting this approach. Besides, several pharma companies are diligently working to bring novel pipeline therapies into the market. Thus, the market offers more elbow room to pharma players to exploit the approach and bring newer ones to grab the maximum market share.