Safety and Efficacy of BAY 1817080, a P2X3 Receptor Antagonist, in Patients with Refractory Chronic Cough (RCC)

Morice, AH; Smith, Jaclyn A.; McGarvey, Lorcan; Birring, SS; Parker, Sean; Turner, AM; Gashaw, Isabella; Fels, Lueder; Klein, Stefan; Francke, Klaus; Friedrich, Christian

doi:10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7648

Cited by 10 publications

(11 citation statements)

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“…[48][49][50] The results from the BAY1817080 phase 1/2a double-blind, placebocontrolled, randomized, 2-way crossover trial (NCT03310645) was presented at the American Thoracic Society International conference virtually in August 2020. 51 Reported results found BAY1817080…”

Section: Gefapixantmentioning

confidence: 99%

Updates in treatment of adults with chronic cough

2020

Am J Manag Care

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Chronic cough is the most common symptom for which individuals seek medical advice. This health issue has a substantial impact on a person's quality of life and can produce complications such as vomiting, fractures, muscle pain, syncope, and depression. Pharmacists and managed care professionals should recognize the complicated etiology of chronic cough and its difficult management. As there are currently no available therapies specifically indicated for this, the emerging treatment options that are targeted for patients with chronic cough have the promising potential to fulfill unmet needs in this population. They will resolve or minimize the significant burden on healthcare resources, families, work, and school, and improve patients' overall health. Statement of Educational Need Chronic cough is a highly debilitating condition that can result from multiple etiologies or is sometimes due to unknown causes. Further, there are no FDA-approved agents at this time that specifically address chronic cough. Combined with a lack of robust efficacy for agents used to treat acute cough, there is a significant unmet need for efficacious agents that provide relief for patients with chronic cough. To address these concerns, new agents with novel mechanisms of action are in development and, if found safe and effective, could become available in the United States. Therefore, healthcare professionals require continuing professional education and application of this knowledge to improve chronic cough management, clinical decision making, and the quality of life among patients affected. Educational Objectives At the completion of this activity, participants will be able to: • Examine the etiologies of chronic cough, the burden, and the pathophysiology. • Explain the treatment options for chronic cough including the emerging therapies. • Identify opportunities to improve the management of chronic cough from a payer and patient perspective, as well as to integrate new treatments into the existing treatment algorithm. Accreditation Statement Pharmacy Times Continuing Education™ is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 3.0 contact hours (0.3 CEU) under the ACPE universal activity number 0290-0000-20-214-H01-P. The activity is available for CE credit through October 15, 2021. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians' Education Resource ® , LLC and Pharmacy Times Continuing Education™. Physicians' Education Resource ® , LLC is accredited by the ACCME to provide continuing medical education for physicians. Physicians' Education Resource ® , LLC, designates this journal-based CME activity for a maximum of 3.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Phys...

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Section: Gefapixantmentioning

confidence: 99%

Updates in treatment of adults with chronic cough

2020

Am J Manag Care

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“…BAY1817080 was recently investigated in a phase I/II proof‐of‐concept trial in patients with RCC (NCT03310645) 71 . Significant reductions in 24‐hour cough frequency were observed at higher doses, with the frequency of taste‐related AEs ranging from 5% to 21% across dose levels ( Table 1 ).…”

Section: Targets For Treatment Of Rcc and Uccmentioning

confidence: 99%

Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough

Mazzone

McGarvey

2020

Clin Pharma and Therapeutics

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Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over-the-counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3-receptor antagonists, voltage-gated sodium channel blockers, neuromodulators, and neurokinin-1-receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.

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“…In light of published and ongoing promising data with at least four clinical programs involving P2X3 receptor-antagonists in treating chronic refractory cough (90)(91)(92)(93)(94)(95)(96)(97)(98), and with extracellular ATP and its receptors having been shown to modulate tumor development, invasion progression, and tumor microenvironment, P2X receptor antagonists may be expected also to exert an antitussive effect in lung cancerrelated cough. Further studies in this area are eagerly awaited.…”

Section: Cancer-related Coughmentioning

confidence: 99%

P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer — A Mini Review

et al. 2021

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Symptoms associated with lung cancer mainly consist of cancer-associated pain, cough, fatigue, and dyspnea. However, underlying mechanisms of lung cancer symptom clusters remain unclear. There remains a paucity of effective treatment to ameliorate debilitating symptoms and improve the quality of life of lung cancer survivors. Recently, extracellular ATP and its receptors have attracted increasing attention among researchers in the field of oncology. Extracellular ATP in the tumor microenvironment is associated with tumor cell metabolism, proliferation, and metastasis by driving inflammation and neurotransmission via P2 purinergic signaling. Accordingly, ATP gated P2X receptors expressed on tumor cells, immune cells, and neurons play a vital role in modulating tumor development, invasion, progression, and related symptoms. P2 purinergic signaling is involved in the development of different lung cancer-related symptoms. In this review, we summarize recent findings to illustrate the role of P2X receptors in tumor proliferation, progression, metastasis, and lung cancer- related symptoms, providing an outline of potential anti-neoplastic activity of P2X receptor antagonists. Furthermore, compared with opioids, P2X receptor antagonists appear to be innovative therapeutic interventions for managing cancer symptom clusters with fewer side effects.

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Safety and Efficacy of BAY 1817080, a P2X3 Receptor Antagonist, in Patients with Refractory Chronic Cough (RCC)

Cited by 10 publications

References 0 publications

Updates in treatment of adults with chronic cough

Updates in treatment of adults with chronic cough

Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough

P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer — A Mini Review

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