A new publication from Afferent Pharmaceuticals’ Phase 2 clinical trial results entitled “P2X3 Receptor Antagonist (AF-219) in Refractory Chronic Cough: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study” was published in The Lancet by Dr. Rayid Abdulqawi, part of Prof. Jaclyn A Smith’s group from the Education and Research Centre, University Hospital of South Manchester, UK, and colleagues. In this study, Afferent’s experimental drug AF-219 reduced daytime cough frequency by 75% compared to a placebo for patients who have treatment-refractory chronic cough.
Previous preclinical studies suggested that airway vagal afferent nerves express P2X3 receptors, which may lead to the hypersensitisation of sensory neurons and contribute to chronic cough. The ATP molecule is released by tissues that are inflamed, injured, or stressed, and seems to be the unique ligand for P2X3 receptors. In this study researchers evaluated the effect AF-219, a first-class oral antagonist of P2X3, in reducing cough rate in patients with refractory chronic cough. The authors did a double-blind, placebo-controlled, two-period crossover study with 24 patients at one UK center. The patients recruited for this study were coughing on average around 40 times per hour over 10 years. The patients with refractory chronic cough were randomly distributed to be treated with AF-219, 600 mg two times per day, or to placebo (1:1). After a 2 week washout, the patients were given the other treatment. The researchers evaluated as the primary endpoint the rate of cough during the day at baseline and after 2 weeks of treatment using 24-hour ambulatory cough recordings. The secondary endpoints parameters such as cough severity, urge to cough, quality of life, and global ratings of change, were quantified by the outcomes reported by the patients.
“Patients with refractory cough suffer from debilitating coughing and need new treatment options. Current therapies are largely ineffective, or can have significant side effects or potential for abuse, since most contain opioids or opiate-derivatives,” commented Jacly Smith, M.B., Ch.B., MRCP, Ph.D., lead author of the Lancet article, and professor and honorary consultant at University Hospital Manchester NHS Foundation Trust, in a press release. “This is the first published study showing clear clinical benefit of a treatment for refractory cough. I am excited by these clinical results and believe that AF-219 represents a promising new antitussive.”
“The remarkable findings in cough, as published in The Lancet, provide the first evidence that AF-219 may be able to reduce chronic coughing in patients whose nerve fibers have been hyper-sensitized. As a selective, oral and non-narcotic agent, we hope that AF-219 will enhance patients’ treatment options. With approximately two-thirds of responders to AF-219 treatment showing more than a 50% reduction in cough frequency, we plan to advance the development of AF-219 by initiating a Phase 2b study in patients with chronic cough early next year and to initiate other studies in preparation for registration studies,” said Kathleen Sereda Glaub, Afferent’s chief executive officer.
The AF-219 is a non-narcotic and orally given drug that exerts its effects selectively using the mechanisms by which some nerve fibers become hyper-sensitized, leading to chronic and debilitating symptoms such as cough.
Afferent Pharmaceuticals is a leading clinical-stage biotechnology company in the development of first-in-class, small molecule compounds that bind P2X3 receptors to be used for the therapy of respiratory and urologic disorders. In the beginning of 2015, Afferent plans to initiate a Phase 2b clinical trial based on AF-219 findings.