Last update 04 Oct 2024
BI-1265162
Last update 04 Oct 2024
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms BI 1265162, BI1265162 |
Target |
Mechanism ENaC blockers(Epithelial sodium channel blockers) |
Therapeutic Areas |
Active Indication- |
Inactive Indication |
Originator Organization |
Active Organization- |
Inactive Organization |
Drug Highest PhaseDiscontinuedPhase 2 |
First Approval Date- |
Regulation- |
Related
5
Clinical Trials associated with BI-1265162Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Intravenous Administration (Part 1) and Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Oral Administration (Part 2) in Healthy Male Subjects Following a Non-randomized, Open-label, Single-dose, Single Arm Per Trial Part Mass Balance Design
A Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Evaluate Efficacy and Safety of Twice Daily Inhaled Doses of BI 1265162 Delivered by Respimat® Inhaler as add-on Therapy to Standard of Care Over 4 Weeks in Patients With Cystic Fibrosis - BALANCE - CF™ 1
Absolute Bioavailability of BI 1265162 Following Oral and Inhaled Administration in Healthy Male Volunteers (an Open-label, Randomised, Single-dose, Three-period, Three-sequence Crossover Study Followed by a Fixed Treatment)
100 Clinical Results associated with BI-1265162
Login to view more data
100 Translational Medicine associated with BI-1265162
Login to view more data
100 Patents (Medical) associated with BI-1265162
Login to view more data
6
Literatures (Medical) associated with BI-126516201 Jun 2024Journal of Cystic Fibrosis
ETD001: A novel inhaled ENaC blocker with an extended duration of action in vivo
Article
Author: Danahay, Henry ; Schofield, Thomas ; Gosling, Martin ; Salathe, Matthias ; McCarthy, Clive ; Collingwood, Stephen P ; Charlton, Holly ; Fox, Roy ; Sabater, Juan ; Baumlin, Nathalie ; Lilley, Sarah
BACKGROUND:
Inhibiting ENaC in the airways of people with cystic fibrosis (pwCF) is hypothesized to enhance mucociliary clearance (MCC) and provide clinical benefit. Historically, inhaled ENaC blockers have failed to show benefit in pwCF challenging this hypothesis. It is however unknown whether the clinical doses were sufficient to provide the required long duration of action in the lungs and questions whether a novel candidate could offer advantages where others have failed?
METHODS:
Dose-responses with the failed ENaC blockers (VX-371, BI 1265162, AZD5634, QBW276) together with ETD001 (a novel long acting inhaled ENaC blocker) were established in a sheep model of MCC and were used to predict clinically relevant doses that would provide a long-lasting enhancement of MCC in pwCF. In each case, dose predictions were compared with the selected clinical dose.
RESULTS:
Each of the failed candidates enhanced MCC in the sheep model. Translating these dose-response data to human equivalent doses, predicted that substantially larger doses of each candidate, than were evaluated in clinical studies, would likely have been required to achieve a prolonged enhancement of MCC in pwCF. In contrast, ETD001 displayed a long duration of action (≥16 h) at a dose level that was well tolerated in Phase 1 clinical studies.
CONCLUSIONS:
These data support that the ENaC blocker hypothesis is yet to be appropriately tested in pwCF. ETD001 has a profile that enables dosing at a level sufficient to provide a long duration of action in a Phase 2 clinical study in pwCF scheduled for 2024.
01 Feb 2024European journal of medicinal chemistry
Discovery and development of BI 1265162, an ENaC inhibitor for the treatment of cystic fibrosis
Article
Author: Linehan, Brian ; Braun, Clemens ; Kley, Jörg T ; Veser, Thomas ; Linz, Günter ; Sieger, Peter ; Heckel, Armin ; Wiedenmayer, Dieter ; Betzemeier, Bodo
Lung selective inhibition of the endothelial sodium channel (ENaC) is a potential mutation agnostic treatment of Cystic Fibrosis (CF). We describe the discovery and development of BI 1265162, the first ENaC inhibitor devoid of the amiloride structural motif that entered clinical trials. The design of BI 1265162 focused on its suitability for inhalation via the Respimat® Soft Mist™ Inhaler and a long duration of action. A convergent and scalable route for the synthesis of BI 1265162 as dihydrogen phosphate salt is presented, that was applied to support clinical trials. A phase 2 study with BI 1265162 did not provide a clear sign of clinical benefit. Whether ENaC inhibition will be able to hold its promise for CF patients remains an open question.
01 Feb 2022The European respiratory journalQ1 · MEDICINE
Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF 1, a randomised, phase II study
Q1 · MEDICINE
Article
Author: Davies, Jane C ; Jain, Raksha ; Fajac, Isabelle ; Hsu, Ming-Chi ; Seibold, Wolfgang ; Mall, Marcus A ; Gupta, Abhya ; Sutharsan, Sivagurunathan ; Goss, Christopher H
Background:
Inhibition of the epithelial sodium channel (ENaC) in cystic fibrosis (CF) airways provides a mutation-agnostic approach that could improve mucociliary clearance in all CF patients. BI 1265162 is an ENaC inhibitor with demonstrated pre-clinical efficacy and safety already demonstrated in humans.
Objective:
We present results from BALANCE-CFTM 1, a phase II, placebo-controlled, randomised, double-blind study of four dose levels of BI 1265162 versus placebo for 4 weeks on top of standard of care in adults and adolescents with CF.
Results:
Initially, 28 randomised subjects (BI 1265162 200 µg twice daily n=14, placebo twice daily n=14) were assessed at an interim futility analysis. Compared with placebo, numerical changes of –0.8% (95% CI –6.6 to 4.9%) in percentage predicted forced expiratory volume in 1s (ppFEV1) and +2.1 units (95% CI –2.4 to 6.5 units) in lung clearance index (LCI) were observed in the active group, meeting a pre-defined stopping rule; accordingly, the study was terminated. Recruitment had continued during the interim analysis and pending results; 24 patients were added across three dose levels and placebo. The final results including these patients (+1.5% ppFEV1, 200 µg twice-daily dose versus placebo) were not supportive of relevant clinical effect. Furthermore, LCI change was not supportive, although interpretation was limited due to insufficient traces meeting quality criteria. A 9.4-point improvement in the Cystic Fibrosis Questionnaire – Revised Respiratory Domain was observed in the 200 µg twice daily dose group versus placebo. BI 1265162 up to 200 µg twice daily was safe and well-tolerated. Pharmacokinetics were similar to those in healthy volunteers.
Conclusion:
BI 1265162 was safe, but did not demonstrate a potential for clinical benefit. Development has been terminated.
1
News (Medical) associated with BI-1265162100 Deals associated with BI-1265162
Login to view more data
R&D Status
10 top R&D records. to view more data
Login
| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Cystic Fibrosis | Phase 2 | US | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | BE | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | CA | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | FR | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | DE | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | ES | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | SE | 16 Sep 2019 | |
| Cystic Fibrosis | Phase 2 | GB | 16 Sep 2019 |
Login to view more data
Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
Phase 1 | - | 12 | (BI 1265162 as Infusion (R)) | pgrsnnmmcm(nuijaptrip) = wixprzqdxk rewzaqmyas (vlxvgownnw, ttkkeqtbgi - pviyajkxuf) View more | - | 06 Jul 2022 | |
(BI 1265162 as Oral Solution (T1)) | pgrsnnmmcm(nuijaptrip) = vxxbgyxxav rewzaqmyas (vlxvgownnw, pbsjvwkzsk - yljxvmefkc) View more | ||||||
Phase 1 | - | 50 | (Placebo Matching BI 1265162) | kaobjxjfuf(idhjxqzvlg) = vwrgxeqqjt qgihlwclsm (dvzwijnstw, eezsvgbduz - dvdpztriok) View more | - | 23 Feb 2022 | |
(10 Microgram (μg) BI 1265162) | kaobjxjfuf(idhjxqzvlg) = vrfwzmbvyc qgihlwclsm (dvzwijnstw, qvnymhnkew - gapzdvtffu) View more | ||||||
Phase 1 | - | 57 | (3 Microgram BI 1265162) | ftpegtqwlh(temgalnmnb) = exzdycilix zlmdkgzfio (thvewlxbhs, gkehdlvuwf - bcvybucnst) View more | - | 23 Feb 2022 | |
(10 Microgram BI 1265162) | ftpegtqwlh(temgalnmnb) = rpxvnzbkdj zlmdkgzfio (thvewlxbhs, yfcbknnmrx - phcxraxsuw) View more | ||||||
Phase 1 | - | 7 | dywvwqsgdm(hxkqiuftqq) = jecufbmvkl dsruraaval (wixhjfvexq, pzxwpdejtf - zrtdhluggz) View more | - | 23 Feb 2022 | ||
Phase 2 | 28 | httizfaohi(oqvovskcny) = tickxloyvu ogaipsmbsg (vtuvlzsqup, -6.6 to 4.9) View more | Negative | 12 Aug 2021 | |||
placebo | - | ||||||
Phase 2 | 52 | Placebo | owzbcsdwvs(vizmdaprcn) = axbxjaujdb fgvsmcswwg (eeslpzmknp, ubpcgauadf - dodjkqftjg) View more | - | 04 Jun 2021 | ||
Phase 1 | - | - | bexdxcbdol(euwbednddp) = Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. zdrfzfitqo (bdfposvlyp ) | Positive | 01 Feb 2021 |
Login to view more data
Translational Medicine
Boost your research with our translational medicine data.
login
or
Deal
Boost your decision using our deal data.
login
or
Core Patent
Boost your research with our Core Patent data.
login
or
Clinical Trial
Identify the latest clinical trials across global registries.
login
or
Approval
Accelerate your research with the latest regulatory approval information.
login
or
Regulation
Understand key drug designations in just a few clicks with Synapse.
login
or
Chat with Hiro
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Start your data trial now!
Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.
Bio
Bio Sequences Search & Analysis
Sign up for free
Chemical
Chemical Structures Search & Analysis
Sign up for free