Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough

Abstract

AIM: We conducted this systematic review and meta-analysis to investigate the efficacy and safety of gefapixant, a novel P2X3 receptor antagonist, in patients with chronic cough. METHODS: We searched four databases for randomized controlled trials (RCTs). We assessed the cough frequency, severity, total Leicester cough questionnaire (LCQ) score, and adverse events. We analyzed the data using Open Meta-Analyst and Review Manager Software. RESULTS: We included four unique studies (comprising five stand-alone RCTs) with 439 patients. Compared to placebo, gefapixant had positive anti-tussive effects by improving awake cough frequency (mean difference [MD] = −5.27, 95% confidence interval [CI] [−6.12, −4.42], P < 0.00001), night cough frequency (MD = −3.71, 95% CI [−6.57, −0.85], P = 0. 01), 24 h cough frequency (MD = −4.18, 95% CI [−5.01, −3.36], P < 0.00001), cough severity using the Visual Analog Scale (MD = −13.36, 95% CI [−17.80, −8.92], P < 0.00001), cough severity diary (MD = −0.88, 95% CI [−1.25, −0.51], P < 0.00001), and total LCQ score (MD = 2.00, 95% CI [1.15, 2.86], P = 0. 00001). Meta-regression analyses showed a positive correlation between the gefapixant dose and the incidence of any adverse event (relative risk [RR] = 0.239, 95% CI [0.093, 1.839], P = 0.001) and incidence of adverse event related to treatment (RR = 0.520, 95% CI [0.117, 0.922], P = 0.011). CONCLUSIONS: In patient with chronic cough, gefapixant exhibits favorable anti-tussive outcomes by improving the cough frequency, severity, and quality of life. While gefapixant is largely tolerable, its side effects (notably taste alteration) are dose dependent.

ATP, an attractive target for the treatment of refractory chronic cough

“…A range of clinical studies have been undertaken leading to two phase III trials which have recently been successfully completed. They confirmed its antitussive efficacy and regulatory approval is expected shortly for the treatment of RCC in practice [ 86 ].…”

Platelets and the Role of P2X Receptors in Nociception, Pain, Neuronal Toxicity and Thromboinflammation

“…Furthermore, gefapixant was shown to reduce cough frequency by diminishing the reflex sensitivity of patients with refractory chronic cough (RCC) two phase III studies [ 131 ]. However, dose-dependent taste-related adverse events were reported [ 132 ]. Interestingly, the more selective P2X 3 receptor antagonist eliapixant reduced cough frequency and severity as well, while taste-related side effects were lower at therapeutic doses than with the less selective P2X 3 receptor antagonist gefapixant [ 133 ].…”

Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19

“…P2X3 receptor (P2X3R), the ATP-gated ion channel, is expressed predominantly on peripheral sensory nerves and fibers that innervate the airways [ 154 ]. Histamine and ATP stimulate cough reflex through P2X3Rs [ 155 ]. The role of ATP and P2X3R in pain and inflammation has been reported previously [ 156 , 157 ].…”

“…A meta-analysis by Abu-Zaid et al. revealed the effectiveness of gefapixant in ameliorating frequency and severity of cough and quality of life [ 155 ]. Two weeks high-dose (600 mg/BID) gefapixant trial diminished cough by 75% [ 154 ].…”