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Afferent Pharmaceuticals Reports
Positive Phase 2 Clinical Data for the Company’s Lead P2X3 Antagonist,
AF-219- Study Showed AF-219 Reduced Daytime Cough Frequency by 75% in Patients with Treatment-Refractory Chronic Cough - New Findings Featured in Late-Breaking Oral Presentation at the European Respiratory Society (ERS) Annual Congress 2013 in Barcelona, Spain - AF-219 Also Being Studied in Phase 2 Trials in Patients with Osteoarthritis Pain and with Interstitial Cystitis/Bladder Pain Syndrome Barcelona, Spain, September 9, 2013 – Afferent Pharmaceuticals today announced positive clinical efficacy results from the Phase 2 study of the Company’s first-in-class oral P2X3 antagonist, AF-219, in patients with treatment-refractory chronic cough. Afferent is a clinical-stage biopharmaceutical company leading the development of first-in-class, proprietary, small molecule compounds that target P2X3 receptors for the treatment of chronic pain, respiratory and urological conditions. In a randomized, double-blind, placebo-controlled, crossover Phase 2 clinical study, AF-219, dosed orally twice daily, was demonstrated to markedly reduce daytime cough frequency by an unprecedented 75% at week 2 of treatment (as measured using an ambulatory sound monitoring system) in patients with treatment-refractory chronic cough (p< 0.001). The study results were featured today in a late-breaking oral presentation titled, "Inhibition of ATP-gated P2X3 channels by AF-219: An effective anti-tussive mechanism in chronic cough" (Abstract No. 1965), at the European Respiratory Society (ERS) Annual Congress 2013, which is taking place in Barcelona, Spain, September 7 - 11, 2013. According to the study findings, daytime cough frequency reduction was accompanied by concordant, statistically significant improvements compared to placebo across a range of secondary endpoints – cough severity, urge to cough, global rating of change, and responses to the Cough Quality of Life Questionnaire (CQLQ) – at week 2 of treatment. Further, there were no safety concerns identified in the study. "The Phase 2 results provide what we believe is the first demonstration of a statistically significant improvement in objective ambulatory cough frequency following pharmacological intervention," commented Jacky Smith, Ph.D., clinical trial principal investigator and Reader and Honorary Consultant in Respiratory Medicine, University Hospital Manchester NHS Foundation Trust. "No new licensed treatments for cough have appeared in more than 50 years. There is a compelling need for new options given the ineffectiveness of many current treatments and potential for cognitive side effects with certain therapies, such as codeine-containing cough medicines. I look forward to the further progress of this important program in chronic cough." Anthony P. Ford, Ph.D., Afferent’s Chief Scientific Officer, commented, "We are very excited with the findings for AF-219 in chronic cough, which greatly exceed our initial expectations. Further, as far as we are aware, this is the first clinical proof-of-concept study to be completed implicating P2X3 receptor mechanisms in any clinical disease. Based on these and other mechanistic insights, we believe P2X3 receptors may be involved more generally in a number of disorders involving neuronal hypersensitivity." Bruce G. McCarthy, M.D., Chief Executive Officer of Afferent Pharmaceuticals, stated, "The cough study results are important validation for our focus on and approach to P2X3 antagonism. Afferent’s lead candidate has been tested in 164 individuals to date, and based on the overall progress of our clinical programs, we anticipate reporting additional POC data in patients with osteoarthritis pain and with interstitial cystitis/bladder pain syndrome by mid-2014. We also are initiating a challenge study in asthma patients later this year." Treatment-Refractory Chronic Cough Cough is the commonest symptom for which patients seek medical attention, and chronic cough due to any cause affects an estimated 5-18% of the general population. A significant set of patients (20-42% of chronic coughers) is estimated to have cough refractory to treatment of associated conditions, such as gastroesophageal reflux or post-nasal drip. Individuals with treatment-refractory chronic cough often report being distressed, depressed, angry and/or anxious. Nearly 80% feel cough interferes with social activities. There is a significant unmet medical need for effective therapies. P2X3 Receptors, ATP and Neuronal Hypersensitization P2X3 receptors are novel targets, highly specific to unmyelinated, small diameter C fiber afferent (or sensory) nerves that have dense innervations in visceral organs, skin and joints and which transmit pain and other sensations of organ function. (In contrast, P2X3 receptors are absent in higher brain centers.) ATP, released by stressed, inflamed or injured tissues, has been found to be the sole ligand for P2X3 receptors, and overstimulation with ATP can cause hypersensitization and overactivity of the C fiber afferent nerves, which in turn can lead to diverse conditions depending on the location of the affected fibers. Topical application of ATP evokes pain in clinical investigations, and its inhalation produces cough, breathlessness and bronchospasm in patients with asthma. In preclinical in vivo models of airways disease, P2X3 receptors sensitize vagal afferents, and P2X3 blockade can reverse both ATP- and histamine-induced potentiation of citric acid induced cough. As a science-driven company, Afferent is evaluating whether blocking P2X3 receptors can normalize hypersensitized neurons and their dysfunctional target organs. Afferent is advancing its proprietary first-in-class P2X3 antagonists in patient studies in a range of disease conditions in which hypersensitized neurons may have an important role in pathophysiology. Once the Company has determined that P2X3 antagonists can help patients (including which types of patients), Afferent will focus on learning how to best use P2X3 antagonists to treat human disease. About Afferent Pharmaceuticals Afferent Pharmaceuticals is a clinical-stage biopharmaceutical company leading the development of first-in-class, small molecule compounds that target P2X3 receptors for the treatment of chronic pain, respiratory and urological conditions. Afferent’s singular focus and industry-leading position on P2X3 antagonism enables the Company to widely explore this novel mechanism of action and evaluate its utility in a broad range of indications. These indications include chronic pain in the joints, hyperresponsive airways (chronic cough, asthma) and bladder pain and hyperactivity (interstitial cystitis/bladder pain syndrome (IC/BPS), overactive bladder). Founded in December 2009, Afferent is building on over a decade of research on P2X3 antagonists. The Company currently has a lead clinical candidate, AF-219, in mid-stage clinical testing, in addition to next-generation preclinical compounds and a substantial and diverse library of small molecules that selectively target P2X3 receptors. In 2012, Afferent initiated Phase 2 studies of AF-219 in patients with osteoarthritis pain, chronic cough and IC/BPS. Afferent’s differentiated, second-generation P2X3 antagonist, AF-220, is expected to complete IND-enabling studies in 2014. Afferent Pharmaceuticals is located in San Mateo, California. For more information on the Company, please visit Afferent’s website at www.afferentpharma.com. Contact Afferent Pharmaceuticals Dr. Bruce McCarthy Chief Executive Officer (650) 286-1276 Media Contacts: Burns McClellan, Inc. Justin Jackson jjackson @burnsmc.com (212) 213-0006, Ext. 327 |