eliapixant (BAY 1817080) / Evotec - LARVOL DELTA

Investigating Camlipixant P2X3 Selectivity and Taste Disturbance: A Model-Based Dose-Response Meta-Analysis (ATS 2025) - P3 | "Other P2X3 antagonists of different magnitudes of selectivity have been investigated for RCC: sivopixant (262×), eliapixant (13×), gefapixant (1.5×), and filapixant (unknown). In this model-based dose-response meta-analysis, the highly selective P2X3 antagonist camlipixant demonstrated placebo-like rates of dysgeusia over the clinical dose range modelled. After adjusting for relative selectivity, all P2X3 antagonists fell on the same tolerability dose-response curve, and the dosage of camlipixant currently under investigation in the CALM-1 and CALM-2 Phase 3 clinical trials (50 mg BID; NCT05599191, NCT05600777) was predicted to result in substantially lower rates of dysgeusia compared with a similar dosage of gefapixant."

Retrospective data • Chronic Cough • Cough • Renal Cell Carcinoma • Respiratory Diseases

P2X3 and P2X2/3 Receptors Inhibition Produces a Consistent Analgesic Efficacy: A Systematic Review and Meta-Analysis of Preclinical Studies. (PubMed, Eur J Pharmacol) - "P2X3 and P2X2/3 receptor inhibitors showed a good analgesic efficacy in preclinical studies, which was dependent on the pain etiology, pain outcome measured, the drug used and its route of administration. Further research is needed to assess the clinical utility of these preclinical findings."

Journal • Preclinical • Retrospective data • Review • Endometriosis • Gynecology • Immunology • Neuralgia • Oncology • Osteoarthritis • Pain • Rheumatology • Women's Health

Efficacy and safety of eliapixant in endometriosis-associated pelvic pain: the randomized, placebo-controlled phase 2b SCHUMANN study. (PubMed, BMC Womens Health) - P2b | "This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive."

Clinical • Journal • P2 data • P2b data • Chronic Cough • Cough • Diabetic Neuropathy • Endometriosis • Gynecology • Hepatology • Liver Failure • Musculoskeletal Pain • Neuralgia • Overactive Bladder • Pain • Pulmonary Disease • Respiratory Diseases • Women's Health

P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants. (PubMed, Clin Pharmacokinet) - P1 | "Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants."

Journal • P1 data • PK/PD data • Chronic Cough • Cough • Diabetic Neuropathy • Endometriosis • Gynecology • Neuralgia • Overactive Bladder • Pain • Pulmonary Disease • Respiratory Diseases • Women's Health

Benefit-risk profile of P2X3 receptor antagonists for treatment of chronic cough: Dose-response model-based network meta-analysis. (PubMed, Chest) - "When used at safe doses, gefapixant had a favorable risk-benefit profile compared to the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway."

Benefit-risk assessment • Journal • Retrospective data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Promising therapeutic targets for the treatment of urine storage dysfunction: what's the status? (PubMed, Expert Opin Ther Targets) - "The P2×3receptor antagonist, eliapixant, was tested in a randomized controlled clinical trial, was well tolerated but did not meet clinical efficacy endpoints...New drug principles for oxidative stress, purine nucleoside phosphorylase inhibition, and NOX inhibition are still at an experimental stage, and so are soluble guanylate cyclase stimulators. Gene therapy with MaxiK±channels is still an interesting approach but no new trials seem to be in pipeline."

Clinical • Journal • Review • Fibrosis • Gene Therapies • Overactive Bladder • TRPA1 • TRPM8

Mass Balance and Metabolic Pathways of Eliapixant, a P2X3 Receptor Antagonist, in Healthy Male Volunteers. (PubMed, Eur J Drug Metab Pharmacokinet) - P1, P1/2 | "Complete recovery of administered eliapixant-related radioactivity was observed in healthy male subjects with predominant excretion via feces. Eliapixant was almost exclusively cleared by oxidative biotransformation (> 90% of dose), with major involvement of cytochrome P450 3A4. Excretion of parent drug was of minor importance (~ 1% of dose)."

Journal

Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study. (PubMed, Pain) - P2a/2b | "In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG."

Journal • P2a data • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Neuralgia • Pain • Type 2 Diabetes Mellitus

Safety and efficacy of P2X3 receptor antagonist for the treatment of refractory or unexplained chronic cough: A systematic review and meta-analysis of 11 randomized controlled trials. (PubMed, Pulm Pharmacol Ther) - "P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia."

Journal • Retrospective data • Review • Chronic Cough • Cough • Pain • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety of Eliapixant in Overactive Bladder: The 12-Week, Randomised, Placebo-controlled Phase 2a OVADER Study. (PubMed, Eur Urol Focus) - P2 | "OVADER did not meet its clinical efficacy endpoints. Potential reasons include the nonspecific OAB symptom complex, the poorly understood pathophysiology, and the coinciding COVID-19 pandemic."

Journal • P2a data • Infectious Disease • Novel Coronavirus Disease • Overactive Bladder • Urinary Incontinence • Urology

Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis. (PubMed, EClinicalMedicine) - "In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS)...Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS...Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough. National Natural Science Foundation of China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207)."

Journal • Retrospective data • Review • Chronic Cough • Cough • Pain • Pulmonary Disease • Respiratory Diseases • B3GAT1

Potential applications of P2X3 receptor antagonists in the treatment of refractory cough. (PubMed, Respir Med) - "Although review articles summarizing have been published previously, most have focused on their chemical properties rather than their clinical aspects, with some omitting drugs that have been in clinical studies for nearly two years such as Eliapixant and Sivopixant. This article can be used as a reference for the follow-up studies of P2X3 receptor antagonists in chronic cough. Additionally, it also has implications for the clinical focus of the drug and the approaches to relieve some side effects."

Journal • Review • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study. (PubMed, Lung) - P2b | "Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG."

Clinical • Journal • P2b data • Chronic Cough • Cough • Hepatology • Liver Failure • Pulmonary Disease • Respiratory Diseases

SCHUMANN: Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb (clinicaltrials.gov) - P2b | N=215 | Terminated | Sponsor: Bayer | Completed ➔ Terminated; Study terminated by Sponsor

Trial termination • Endometriosis • Gynecology • Pain • Women's Health

Preclinical and Clinical Pharmacokinetics and Bioavailability in Healthy Volunteers of a Novel Formulation of the Selective P2X3 Receptor Antagonist Eliapixant. (PubMed, Eur J Drug Metab Pharmacokinet) - P1 | "The novel eliapixant formulation substantially improved bioavailability compared with immediate-release eliapixant and may be administered with/without food."

Journal • PK/PD data • Preclinical

P2X receptors: Insights from the study of the domestic dog. (PubMed, Neuropharmacology) - "The article will also discuss the characterization of single nucleotide polymorphisms in the canine P2RX7 gene, and contrast this variation to the canine P2RX4 gene, which is largely conserved between dogs. Finally, this article will outline published examples of the use of dogs to study the pharmacokinetics of P2X7 and P2X3 antagonists, and how they have contributed to the preclinical testing of antagonists to human P2X7, CE-224,535, and human P2X3, Gefapixant (AF-219, MK-7264) and Eliapixant (BAY, 1817080), with Gefapixant gaining recent approval for use in the treatment of refractory chronic cough in humans."

Journal • Review • Cardiovascular • Chronic Cough • Cough • Oncology • Pulmonary Disease • Respiratory Diseases

Safety, Pharmacodynamics, and Pharmacokinetics of P2X3 Receptor Antagonist Eliapixant (BAY 1817080) in Healthy Subjects: Double-Blind Randomized Study. (PubMed, Clin Pharmacokinet) - P1/2 | "Eliapixant (200 and 750 mg) produced plasma concentrations that cover the predicted therapeutic threshold over 24 h, with good safety and tolerability. These results enabled eliapixant to progress to clinical trials in patients with refractory chronic cough."

Journal • PK/PD data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Eliapixant in Refractory Chronic Cough: The 12-Week, Randomized, Double-Blind, Placebo-Controlled, Phase 2b PAGANINI Study (ATS 2022) - P2b | "The FAS analysis confirmed results in the PPS. Eliapixant reduced 24-hour cough count, with a positive benefit-risk profile in patients with RCC. There were fewer taste-related AEs in PAGANINI than reported previously in other clinical trials with less selective P2X3 antagonists."

Clinical • P2b data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

SCHUMANN: Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb (clinicaltrials.gov) - P2b | N=194 | Completed | Sponsor: Bayer | Recruiting ➔ Completed | N=420 ➔ 194

Enrollment change • Trial completion • Endometriosis • Gynecology • Pain

First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: tolerability, safety and pharmacokinetics. (PubMed, Br J Clin Pharmacol) - P1 | "The PK profile, particularly the long half-life, and favourable tolerability with no taste-related AEs, supports the further development of eliapixant in disorders with underlying P2X3 receptor-mediated neuronal hypersensitisation."

Journal • P1 data • PK/PD data • Chronic Cough • Cough • Endometriosis • Gynecology • Pulmonary Disease • Respiratory Diseases

SCHUMANN: Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb (clinicaltrials.gov) - P2b | N=420 | Recruiting | Sponsor: Bayer | Trial primary completion date: May 2022 ➔ Jan 2022

Trial primary completion date • Endometriosis • Gynecology • Pain

A 2-part Trial to Learn More About How BAY1817080 Works, How Safe it is, and What the Right Dose is for Participants With Diabetic Neuropathic Pain (clinicaltrials.gov) - P2a/2b | N=154 | Terminated | Sponsor: Bayer | N=441 ➔ 154 | Trial completion date: Jul 2023 ➔ Oct 2021 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2023 ➔ Sep 2021; Lack of efficacy

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

SCHUMANN: Study to Gather Information How Well Three Different Doses of BAY1817080 Given Twice Daily Over 12 Weeks Work in Comparison to an Inactive Pill (Placebo) and Elagolix in Women Suffering From Pain Related to a Condition Where the Tissue That Usually Grows Inside the Womb Grows Outside of the Womb (clinicaltrials.gov) - P2b | N=420 | Recruiting | Sponsor: Bayer | Trial completion date: Dec 2022 ➔ May 2022

Trial completion date • Endometriosis • Gynecology • Pain

Bayer halts development of chronic cough treatment [Google translation] (Newsmp) - "German pharmaceutical company Bayer has abandoned the development of eliapixant (BAY1817080), a new drug candidate being developed as a treatment for chronic cough. Bayer announced on the 4th (local time) that it will discontinue the development of Eliapixant, a P2X3 receptor antagonist, in phase 2 clinical trials, which has been evaluated for indications such as endometriosis, refractory chronic cough, overactive bladder, and diabetic neuropathy pain. After reviewing the available data, the company said it had concluded that the overall benefits of Eliapixant no longer outweigh the risks in these indications."

Discontinued • Chronic Cough • Cough

Bayer halts development of chronic cough treatment candidates Evotech’s market cap fell 1.2 trillion won [Google translation] (News1 Korea) - "Bayer, a multinational pharmaceutical company, has given up on developing a candidate for a chronic cough treatment in phase 2 clinical trials. On the 7th, BioCentury reported that the stock price of Evotech in the US also declined as Bayer returned the rights after ending development of 'Eliapixant (development name: BAY1817080)', a new drug candidate targeting the P2X3 receptor....As a result of Bayer's decision, Evotech's share price fell more than 16% in the Frankfurt stock market on the 4th, resulting in a market cap of about 1.2 billion euros (about 1.64 trillion won). On the same day, Evotech's stock fell about 15% in the US Nasdaq market."

Stock price • Chronic Cough • Cough • Respiratory Diseases