Safety and Efficacy of BAY 1817080 in Patients With Refractory Chronic Cough

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

BAY 1817080, a potent selective P2X3 receptor antagonist, may have utility as a new treatment for refractory chronic cough (RCC), according to the results of a Phase 1/2A study (ClinicalTrial.gov Identifier: NCT03310645) intended to be presented at the American Thoracic Society (ATS) International Conference, but that may be presented in a virtual format later this year.

There are currently no licensed treatments for RCC and off-label pharmacologic treatments have limited efficacy and high adverse event (AE) rates. P2X3 receptors induce dysregulated respiratory tract afferent nerve fiber signaling, and in preclinical models, BAY 1817080 inhibited vagus nerve depolarization. Researchers investigated the preliminary safety and efficacy of BAY 1817080 in 40 adult nonsmokers with RCC for ≥1 year, unresponsive to ≥8 weeks targeted treatment for identified underlying triggers, or with no trigger identified (unexplained chronic cough).

This double-blind, placebo-controlled, randomized study included a 2-way crossover of oral BAY 1817080 (10, 50, 200, and 750 mg twice daily; 7 days each) and matched placebo.

The researchers found that AEs occurred in 41% to49% of patients who received BAY 1817080 and 65% of patients who received placebo, and most were mild. A taste-related AE was seen in 5%, 10%, 15%, and 21% of patients who received BAY 1817080 10, 50, 200, and 750 mg, respectively, and in 3% of patients who received placebo.

Other common AEs included headache (BAY 1817080, 3%-13%; placebo, 15%) and fatigue (BAY 1817080, 3%-5%; placebo, 10%). One placebo patient developed a serious AE (obstructive pancreatitis as a result of cholelithiasis). Higher BAY 1817080 doses decreased 24-hour cough counts with a mean relative reduction vs placebo: 50 mg, 15% (P =.054); 200 mg, 23% (P =.004); and 750 mg, 25% (P = .002). With placebo, cough counts fell from baseline by 17% (P =.025). BAY 1817080 also significantly improved patient-reported cough severity at doses ≥50 mg.

The researchers concluded, “Multiple BAY 1817080 doses up to 750 mg were well-tolerated with low rates of taste-related AEs.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Morice AH, Smith J, McGarvey L, et al. Safety and efficacy of BAY 1817080, a P2X3 receptor antagonist, in patients with refractory chronic cough (RCC). Am J Respir Crit Care Med. 2020;201:A7648.