"Gefapixant"

Gefapixant for treating refractory or unexplained chronic cough (terminated appraisal) Gefapixant for treating refractory or unexplained chronic cough (terminated appraisal) Technology appraisal guidance Published: 30 April 2024 www.nice.org.uk/guidance/ta969 © NICE 2024. All rights reserved. Subject to Notice of rights ( Advice ................................................................................................................................3 Information ..................................................................................................................................3 Gefapixant for treating refractory or unexplained chronic cough (terminated appraisal)(TA969)© NICE 2024. All rights reserved. Subject to Notice of rights ( 2of 3 Advice NICE is unable to make a recommendation about the use in the NHS of gefapixant

Gefapixant (Lyfnua) - chronic (long-term) cough Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The NetherlandsAddress for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000An agency of the European Union © European Medicines Agency, 2023. Reproduction is authorised provided the source is acknowledged.EMA/342744/2023 EMEA/H/C/005476Lyfnua (gefapixant)An overview of Lyfnua and why it is authorised in the EUWhat is Lyfnua and what is it used for?Lyfnua is a medicine used to treat adults with chronic (long-term) cough which is unexplained or for which other treatments have not worked. The medicine contains the active substance gefapixant.How is Lyfnua used?Lyfnua is available

Single- and Multiple-Dose Pharmacokinetics of Gefapixant (MK-7264), a P2X3 Receptor Antagonist, in Healthy Adults. Gefapixant (MK-7264, RO4926219, AF-219) is a first-in-class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single- and multiple-dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single-dose administration of 10-450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter-subject variability and a dose-proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose-proportional at doses ranging from 7.5 to 50 mg and less than dose-proportional at doses

Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial. Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176). From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4

Randomized, controlled, proof-of-concept trial of gefapixant for endometriosis-related pain. To evaluate the P2X3 receptor antagonist, gefapixant, for treating moderate-to-severe endometriosis-related pain. Randomized, double-blind, Phase 2, proof-of-concept trial. Premenopausal women age 18-49y with moderate-to-severe endometriosis-related pain who were not using hormonal treatment. Gefapixant 45mg twice-daily or placebo over two menstrual cycles. Participants rated peak pelvic pain severity daily on a 0 (no pain) - 10 (extremely severe pain) scale. The primary endpoint was change-from-baseline in average daily peak pelvic pain severity during Treatment Cycle 2. All 187 participants randomized (gefapixant N=94, placebo N=93) took ≥1 dose of investigational treatment and all but 6 in each

Efficacy and safety of gefapixant, a P2X(3) receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Gefapixant is an oral P2X receptor antagonist that has previously shown efficacy and safety in refractory chronic cough and unexplained chronic cough. We therefore aim to confirm the efficacy and safety of gefapixant in participants with refractory chronic cough and unexplained chronic cough. COUGH-1 and COUGH-2 were both double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. COUGH-1 was done in 156 sites in 17 countries and COUGH-2 in 175 sites in 20 countries. We enrolled participants who were 18 years or older with a diagnosis

The Efficacy and Safety of Gefapixant in a Phase 3b Trial of Patients with Recent-Onset Chronic Cough. We evaluated gefapixant, a P2X3 receptor antagonist, in participants with recent-onset (≤ 12 months) refractory chronic cough (RCC) or unexplained chronic cough (UCC). Participants (≥ 18 years of age; ≥ 40 mm on a 100-mm cough severity visual analog scale [VAS] at screening and randomization ) with chronic cough for < 12 months were enrolled in this phase 3b, double-blind, placebo-controlled, parallel group, multicenter study (NCT04193202). Participants were randomized 1:1 to gefapixant 45 mg BID or placebo for 12 weeks with a 2-week follow-up. The primary efficacy endpoint was change from baseline at Week 12 in Leicester Cough Questionnaire (LCQ) total score. Adverse events were monitored

Improvements in Objective and Subjective Measures of Chronic Cough with Gefapixant: A Pooled Phase 3 Efficacy Analysis of Predefined Subgroups. In phase 3 trials (COUGH-1/COUGH-2), gefapixant 45 mg twice daily significantly reduced 24-h cough frequency vs placebo in refractory or unexplained chronic cough (RCC or UCC). Here, the efficacy of gefapixant 45 mg vs placebo was evaluated across COUGH -1/COUGH-2 in predefined subgroups based on sex, region, age, cough duration, cough severity, cough frequency, and diagnosis (RCC, UCC). Awake cough frequency reductions at Week 12 and LCQ response rates (i.e., ≥ 1.3-point improvement) at Week 24 were assessed. Among 1360 participants analyzed, gefapixant 45 mg resulted in consistent awake cough frequency reductions overall and across predefined

A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough. In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily (BID), with an acceptable safety profile. The primary objective of this phase 3, randomized, double-blind, parallel-group study was to assess the safety and tolerability of gefapixant in Japanese participants with RCC or UCC (ClinicalTrials.gov, NCT03696108; JAPIC-CTI, 184154). Participants aged ≥20 years with chronic cough lasting ≥4 months

Treatment with the P2X3-Receptor Antagonist Gefapixant for Acute Cough in Induced Viral Upper Respiratory Tract Infection: A Phase 2a, Randomized, Placebo-Controlled Trial. Available therapies for acute cough, a condition frequently caused by a viral upper respiratory tract infection (URTI), have shown limited evidence of efficacy. Gefapixant, a P2X3-receptor antagonist, has demonstrated efficacy and safety in studies of the treatment of refractory or unexplained chronic cough, but its efficacy for treating acute cough has not been previously studied. This was a phase 2a, randomized, double-blind, placebo-controlled, parallel-group, pilot study. Healthy volunteers were randomized 1:1 to receive twice-daily gefapixant 45 mg or placebo and inoculated with human rhinovirus 16 to induce URTI

A Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults. Patients with chronic cough are typically female and have a mean age of ~ 60 years. However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males. The objective of this Phase 1 study was to assess the safety, tolerability, and PK of gefapixant in younger (18-55 years) and older (65-80 years) males and females. A randomized, double-blind, placebo-controlled study was conducted. Healthy adult participants were stratified into 4 cohorts by age

Gefapixant in two randomised dose-escalation studies in chronic cough Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach. Two randomised, double-blind, placebo -controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50-200 mg, study 2: 7.5-50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient

Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Chronic cough is a highly problematic symptom for patients with idiopathic pulmonary fibrosis (IPF); limited therapeutic options are available. We evaluated gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough in IPF. This randomized, double-blind, placebo-controlled, crossover study included subjects with IPF. Sequence A included gefapixant 50 mg BID (period 1; 14 days) followed by placebo (period 2; 14 days); sequence B had the opposite sequence of treatments. This regimen was specified in a protocol amendment that modified the original active treatment regimen of gefapixant 50 mg BID for 10 days

Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Gefapixant is a P2X3 receptor antagonist that has shown promise for the treatment of refractory and unexplained chronic cough. The aim of this study was to evaluate the efficacy of gefapixant compared with placebo after 12 cough lasting 1 year or longer, no radiographic chest abnormality, and 40 mm or more on a 100-mm cough severity visual analogue scale at enrolment. Patients were randomly assigned to receive placebo or one of three doses (7·5 mg, 20 mg, or 50 mg) of oral gefapixant twice daily, every day, for 84 days; visits to investigative sites were on days 1, 28, 42, 56, 70, 84, and 85. The randomisation schedule

Design and rationale of two phase 3 randomised controlled trials (COUGH-1 and COUGH-2) of gefapixant, a P2X3 receptor antagonist, in refractory or unexplained chronic cough. We present study designs, dose selection and preliminary patient characteristics from two phase 3 clinical trials of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough (RCC) or unexplained chronic cough (UCC ). COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are randomised, placebo-controlled, double-blind, parallel-group trials in subjects with RCC or UCC (age ≥18 years; cough duration ≥1 year; Cough Severity Visual Analogue Scale score ≥40 mm). The primary efficacy study periods are 12 weeks (40-week extension; COUGH-1) and 24 weeks (28-week extension; COUGH-2). Interventions include placebo, gefapixant 15

The Effect of Gefapixant, a P2X3 antagonist, on Cough Reflex Sensitivity: A randomised placebo-controlled study. We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge.In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p<0.001) by a factor of 1.4 and 1.3, respectively

Update on the clinical development of gefapixant, a P2X3 receptor antagonist for the treatment of refractory chronic cough. Chronic cough, or cough lasting >8 weeks, is often associated with underlying medical conditions (ie, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, and upper-airway cough syndrome). In some patients with chronic cough, treatment , the adenosine triphosphate (ATP)-gated P2X3 receptor, a key modulator of the activation of sensory neurons central to the cough reflex, has recently garnered attention as a potential therapeutic target for the treatment of chronic cough. Gefapixant, a first-in-class, non-narcotic, selective antagonist of the P2X3 receptor, recently demonstrated efficacy and was generally well tolerated in phase 2 clinical

Efficacy and safety of gefapixant, a novel P2X3 receptor antagonist for the management of chronic cough: a systematic review and meta-analysis. PROSPEROInternational prospective register of systematic reviews Print | PDFEfficacy and safety of gefapixant, a novel P2X3 receptor antagonist for the management of chronic cough: a systematic review and meta-analysis.Abdelrahman Mahmoud Ali Mahmoud registration. Further detail is provided here.CitationAbdelrahman Mahmoud Ali Mahmoud, Basel Abdelazeem, Mohamed Abuelazm. Efficacy and safety of gefapixant, a novel P2X3 receptor antagonist for the management of chronic cough: a systematic review and meta-analysis.. PROSPERO 2023 CRD42023397773 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397773Review questionThe

Effect of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough Recently, a new drug called Gefapixant passed phase III clinical trials for cough suppression in patients with chronic cough. The goal of this clinical trial is to investigate the effect of acute and prolonged administration of the drug Gefapixant on cough-related brain activity in patients with chronic cough . The main question it aims to answer is: does the mechanism of action of Gefapixant on the brainstem and brain circuits regulating cough differ between acute and prolonged therapy in people with chronic cough?Participants have their brain activity and their sensitivity to cough-inducing substances measured as well as complete questionnaires about their cough before and while taking daily Gefapixant

The efficacy and safety of gefapixant on refractory or unexplained chronic cough: a systematic review and meta-analysis PROSPEROInternational prospective register of systematic reviews Print | PDFThe efficacy and safety of gefapixant on refractory or unexplained chronic cough: a systematic review and meta-analysisDongxu Si, Wenfeng He, You Zhou, Shuyun Xiong, Yingna LiTo enable PROSPERO , Wenfeng He, You Zhou, Shuyun Xiong, Yingna Li. The efficacy and safety of gefapixant on refractory or unexplained chronic cough: a systematic review and meta-analysis. PROSPERO 2022 CRD42022373110 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373110Review questionThe aim of this systematic review is conducted to evaluate gefapixant for the treatment of refractory