Gefapixant was approved in Japan in 2022 for adult patients with refractory or unexplained chronic cough, marketed under the name Lyfnua.The drug was authorised by the European Medicines Agency (EMA) in September 2023 for the same indication. However, the FDA refused to approve gefapixant for the treatment of adults with refractory or unexplained chronic cough.
Gefapixant is an orally active and potent purinergic P2X3 receptor (P2X3R) antagonist, with IC50 values of ~30 nM versus recombinant hP2X3 homotrimers and 100-250 nM at hP2X2/3 heterotrimeric receptors. Gefapixant can be used for the research of chronic cough and knee osteoarthritis.
Gefapixen is an orally available, selective P2X3 receptor antagonist used to treat cough-related conditions such as chronic cough and refractory cough. The P2X3 receptor is an ion channel expressed in sensory neurons that plays a key role in the transmission of pain and cough reflexes. Gefapixen reduces the activation of cough receptors by specifically blocking the P2X3 receptor, thereby alleviating cough symptoms.
Gefapixant exerts its therapeutic effects via suppressing the cough reflex initiated by sensory C fibers of the vagus nerve. In clinical studies, patients experienced a significant reduction in 24-hour cough frequency compared to placebo - this reduction was apparent by Week 4 and persisted throughout the remainder of the primary efficacy period.
As renal excretion is the primary route of elimination for gefapixant, patients with severe renal impairment (eGFR < 30 mL/min/1.73m2) may require dose adjustment to maintain appropriate systemic exposures.
Gefapixant (7d bid, orally) attenuates the weight bearing laterality with complete reversal of apparent hyperalgesia at the two higher doses in a rat model of knee osteoarthritis (14d following intra-articular administration of monoiodoacetate)[2].
