Data from the first cohort of patients in the dose-escalation study were presented at the 2016 American Thoracic Society (ATS) International Conference by the trial’s lead investigator, Dr. Jacky Smith, a professor of respiratory medicine at the University of Manchester and University Hospital Manchester NHS Foundation Trust. Data referring to the study’s second cohort, evaluating lower doses of AF-219, is expected to be presented later this year.
The Phase 2b trial included 29 patients with chronic cough (averaging 60 coughs per hour while awake) for a mean of 15 years, and was conducted at 10 different U.S. sites. Patients were randomized to receive either placebo or AF-219 50 mg, followed by dose escalations up to 100, 150, and 200 mg twice-daily. The four-day treatment period was followed by a three-to-seven day washout period. Participants then crossed over to the study’s alternate arm, and were treated with either AF-219 or placebo for 16 days. Evaluation of treatment efficacy was performed through a cough frequency measurement.
Results showed that all AF-219 doses induced a significant decrease in cough frequency. The lowest dose, 50 mg twice daily, was shown to have similar efficacy to the previously evaluated 600 mg dose, results of which were published in The Lancet. Nearly half of the patients on the lowest dose had at least a 50% decrease in cough frequency, and 35% of them had a 70% or greater decrease in cough frequency.
Tolerability results were also positive, and the incidence of dysgeusia (altered taste perception) was much lower in the lowest dose compared to higher doses, and to the 600 mg dose. One patient discontinued treatment due to the taste effect. In total, 57% of the patients in this study noted taste alteration, as compared to 100% in the previous high-dose study. One serious adverse event, a urinary tract infection, was registered during the study.
“We are extremely pleased that this study validates the efficacy we had seen in our previous cough study, and provides critical guidance for Phase 3 dose selection. In addition to presenting the second cohort lower-dose results, we look forward to results from our ongoing 12-week chronic cough study with AF-219 later this year,” Kathleen Sereda Glaub, the company’s CEO, said in a press release. “As we advance development of AF-219, we also plan to evaluate non-respiratory indications in which P2X3 has been implicated, with our next candidate, AF-130.”
Afferent is also exploring the therapeutic effects of AF-219 in idiopathic pulmonary fibrosis (IPF) patients with bothersome cough and breathlessness in an ongoing Phase 2b clinical trial.