Delving into the Latest Updates on BI-1026706 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BI 1026706

Target

B1 receptor

Action

antagonists

Mechanism

B1 receptor antagonists(Bradykinin B1 receptor antagonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [6]

Active Indication-

Inactive Indication

Diabetic macular oedemaInflammationMacular Edema+ [4]

Originator Organization

Boehringer Ingelheim GmbH

Active Organization-

Inactive Organization

Boehringer Ingelheim GmbH

License Organization-

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Bradykinin 1 receptor (B1R) signalling pathways may be involved in the inflammatory pathophysiology of chronic obstructive pulmonary disease (COPD). B1R signalling is induced by inflammatory stimuli or tissue injury and leads to activation and increased migration of pro-inflammatory cells. Lipopolysaccharide (LPS) lung challenge in man is an experimental method of exploring inflammation in the lung whereby interference in these pathways can help to assess pharmacologic interventions in COPD. BI 1026706, a potent B1R antagonist, was hypothesized to reduce the inflammatory activity after segmental lipopolysaccharide (LPS) challenge in humans due to decreased pulmonary cell influx.

METHODS:

In a monocentric, randomized, double-blind, placebo-controlled, parallel-group, phase I trial, 57 healthy, smoking subjects were treated for 28 days with either oral BI 1026706 100 mg bid or placebo. At day 21, turbo-inversion recovery magnitude magnetic resonance imaging (TIRM MRI) was performed. On the last day of treatment, pre-challenge bronchoalveolar lavage fluid (BAL) and biopsies were sampled, followed by segmental LPS challenge (40 endotoxin units/kg body weight) and saline control instillation in different lung lobes. Twenty-four hours later, TIRM MRI was performed, then BAL and biopsies were collected from the challenged segments. In BAL samples, cells were differentiated for neutrophil numbers as the primary endpoint. Other endpoints included assessment of safety, biomarkers in BAL (e.g. interleukin-8 [IL-8], albumin and total protein), B1R expression in lung biopsies and TIRM score by MRI as a measure for the extent of pulmonary oedema.

RESULTS:

After LPS, but not after saline, high numbers of inflammatory cells, predominantly neutrophils were observed in the airways. IL-8, albumin and total protein were also increased in BAL samples after LPS challenge as compared with saline control. There were no significant differences in cells or other biomarkers from BAL in volunteers treated with BI 1026706 compared with those treated with placebo. Unexpectedly, neutrophil numbers in BAL were 30% higher and MRI-derived extent of oedema was significantly higher with BI 1026706 treatment compared with placebo, 24 h after LPS challenge. Adverse events were mainly mild to moderate and not different between treatment groups.

CONCLUSIONS:

Treatment with BI 1026706 for four weeks was safe and well-tolerated in healthy smoking subjects. BI 1026706 100 mg bid did not provide evidence for anti-inflammatory effects in the human bronchial LPS challenge model.

TRIAL REGISTRATION:

The study was registered on January 14, 2016 at ClinicalTrials.gov (NCT02657408).

30 Mar 2020·Translational vision science & technologyQ3 · MEDICINE

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema

Q3 · MEDICINE

ArticleOA

Author: Weiss-Haljiti, Cornelia ; Tadayoni, Ramin ; Lang, Gabriele E. ; Tang, Wenbo ; Chong, Victor ; Barth, Claudia

Purpose:

The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema.

Methods:

Patients (n = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics.

Results:

After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups.

Conclusions:

BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema.

Translational Relevance:

Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.

PharmaceuticsQ3 · MEDICINE

Quantification of Drugs in Distinctly Separated Ocular Substructures of Albino and Pigmented Rats

Q3 · MEDICINE

ArticleOA

Author: Schönberger, Tanja ; Garneau, Michel ; Sauer, Achim ; Baum-Kroker, Katja S. ; Runge, Frank ; Rimpelä, Anna-Kaisa

The rat is a commonly used species in ocular drug research. Detailed methods of separating rat ocular tissues have not been described in literature. To understand the intraocular drug distribution, we developed a robust method for the separation of individual anterior and posterior substructures of pigmented Brown Norway (BN) and albino Wistar Han (WH) rat eyes, followed by quantification of drug concentration in these substructures. A short formalin incubation, which did not interfere with drug quantification, enabled the preservation of individual tissue sections while minimizing cross-tissue contamination, as demonstrated by histological analysis. Following oral administration, we applied the tissue separation method, in order to determine the ocular concentrations of dexamethasone and levofloxacin, as well as two in-house molecules BI 113823 and BI 1026706, compounds differing in their melanin binding. The inter-individual variability in tissue partitioning coefficients (Kp) was low, demonstrating the reproducibility of the separation method. Kp values of individual tissues varied up to 100-fold in WH and up to 46,000-fold in BN rats highlighting the importance of measuring concentration directly from the ocular tissue of interest. Additionally, clear differences were observed in the BN rat tissue partitioning compared to the WH rat. Overall, the developed method enables a reliable determination of small molecule drug concentrations in ocular tissues to support ocular drug research and development.

1

News (Medical) associated with BI-1026706

12 May 2021

·www.globenewswire.com

Diabetic Macular Edema Pipeline Sees Expansion Owing to Key

Los Angeles, USA, May 12, 2021 (GLOBE NEWSWIRE) -- Diabetic Macular Edema Pipeline Sees Expansion Owing to Key Players, Key Therapies and Research & Programmes Diabetic Macular Edema Pipeline Insight report offers deep insights into emerging Diabetic Macular Edema pipeline therapies with an analysis of 50+key players and 50+key therapies. DelveInsight’s ‘Diabetic Macular Edema (DME) Pipeline Insights’ report provides a holistic view of the DME pipeline therapies that are under development in pre-clinical as well as clinical stages of development and growth prospects across the Diabetic Macular Edema landscape. Key takeaways of the Diabetic Macular Edema Pipeline report: Got queries? Want to know more? Request for Sample @ Diabetic Macular Edema Emerging Therapies and Forecast Diabetic Macular Edema: Overview Macular edema is a condition characterized by the build-up of fluid in the macula, an area in the center of the retina. The excess build-up results in the swelling and thickening of the macula leading to distorted vision. It is referred to as Diabetic Macular Edema (DME) as it is caused by a complication of diabetes called diabetic retinopathy. For more information on emerging drugs, visit Diabetic Macular Edema Pipeline Analysis The DME pipeline report proffers a rich coverage of the therapeutics by development stage, product type, and route of administration, molecule type, and MOA type for Diabetic Macular Edema across the complete product development cycle, including all clinical and non-clinical stages. Diabetic Macular Edema Pipeline Drugs Request for Sample to know which drug is expected to outperform @ Diabetic Macular Edema Pipeline Analysis, Key Companies, and Futuristic Trends Diabetic Macular Edema Therapeutics Assessment The Diabetic Macular Edema Pipeline report proffers exhaustive insights into active pipeline assets segmented by Stage, Product Type, Route of Administration, Molecule Type, Target, and Indications of various drugs. By Product Type By Stage By Molecule Type By Route of Administration By Mechanism of Action By Targets By Stage and Route of AdministrationBy Stage and Product Type Get in touch with our Business executive for Rich and Deep Market Assessment and Consulting Solutions The Diabetic Macular Edema pipeline report puts on the table business opportunities, threats, prospective collaborations, strong competitors, growth strategies, and failed as well as discontinued drugs that will help the clients to keep a track of the ongoing trials, recent happenings in the DME domain. Scope of the Report Coverage: GlobalKey Players: Kodiak Sciences, Novartis Pharmaceuticals, Adverum Biotechnologies, KalVista Pharmaceuticals, Momenta Pharmaceuticals, Roche, Regeneron Pharmaceuticals, Exonate, Opthea Limited, SciFluor Life Sciences, AsclepiX Therapeutics, RemeGen, UNITY Biotechnology, Celltrion, Bio-Thera Solutions, Ripple Therapeutics, GrayBug Vision, Oxurion, Aerie Pharmaceuticals, GlaxoSmithKline, Boehringer Ingelheim, and Apexian Pharmaceuticals among others.Key Diabetic Macular Edema Pipeline Therapies: KSI 301, LKA651, ADVM-022, KVD001, MYL-1701P, Faricimab, REGN 910-3, EXN407, OPT-302, SF0166, AXT107, Brolucizumab, RC28-E, UBX1325, CT-P42, BAT5906, IBE-814, GB-102, THR-149, AR-13503, GSK2798745, BI 1026706, and APX3330 among others. Reach out how novel therapies are transforming the DME landscape @ Diabetic Macular Edema Pipeline Table of Contents Visit to know more of what’s covered @ Diabetic Macular Edema Emerging Therapies Related Reports Chronic Pain Associated With Painful Diabetic Neuropathy MarketDelveInsight's "Chronic Pain Associated with Painful Diabetic Neuropathy - Market Insights, Epidemiology, and Market Forecast-2030" report. Diabetic Foot Ulcers MarketDelveInsight’s ‘Diabetic Foot Ulcer (DFU) - Market Insights, Epidemiology, and Market Forecast—2030’ report. Diabetic Foot MarketDelveInsight's "Diabetic Foot - Market Insights, Epidemiology, and Market Forecast-2030" report. Diabetic Eye Disease MarketDelveInsight's "Diabetic Eye Disease - Market Insights, Epidemiology, and Market Forecast-2030" report. Diabetic Ketoacidosis MarketDelveInsight's "Diabetic Ketoacidosis (DKA) - Market Insights, Epidemiology, and Market Forecast-2030" report. Diabetic Gastroparesis Market SizeDelveInsight’s ‘Diabetic Gastroparesis (DGp) - Market Insights, Epidemiology and Market Forecast-2030’ report offers a detailed analysis of therapies and key pharmaceutical companies including Allergan Evoke Pharma Inc., Theravance Biopharma, Censa Pharmaceuticals, CinDome Pharma, Takeda (Millennium Pharmaceuticals, Inc.), Bird Rock Bio, and others. Diabetic Kidney Disease MarketDelveInsight's "Diabetic Kidney Disease (DKD) - Market Insights, Epidemiology, and Market Forecast-2030" report. Related Posts Understanding The Increasing Prevalence Of Diabetes And Its ComplicationsDiabetic Peripheral Neuropathy Market Landscape Diabetic Peripheral Neuropathy Medications About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing end-to-end comprehensive solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. For more insights, visit Pharma, Healthcare, and Biotech News

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100 Deals associated with BI-1026706

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic macular oedema	Phase 2	Belgium	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	France	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	Germany	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	Greece	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	Hungary	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	Portugal	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	Spain	Boehringer Ingelheim GmbH	14 Apr 2016
Diabetic macular oedema	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	14 Apr 2016
Macular Edema	Phase 2	Belgium	Boehringer Ingelheim GmbH	14 Apr 2016
Macular Edema	Phase 2	France	Boehringer Ingelheim GmbH	14 Apr 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02732951 (1320.22, Pubmed \| Transl Vis Sci Technol) Manual	Phase 2	Diabetic macular oedema	105	BI 1026706	ecnghmijml(kqvkluvjan) = qszjznstwn kxzhpzgmcj (hxdsuwkpla )	Negative	30 Mar 2020
				Placebo	ecnghmijml(kqvkluvjan) = tivpoqajet kxzhpzgmcj (hxdsuwkpla )
NCT02642614 (CTgov)	Phase 1	Pulmonary Disease, Chronic Obstructive \| Inflammation	120	Placebo	bmgkpmhurm = jhyarigfdq kqezlwfghf (ensfcqypnr, johumabvkg - trnklkvfuq) View more	-	05 Aug 2019
NCT02652416 (CTgov)	Phase 1	-	72	placebo (Placebo)	pblbuucxnj = kzlqibgdlj kkvobldnms (ndhtvtxmon, vrutonojsv - cnskfychwo) View more	-	11 Jul 2019
				BI 1026706 (BI 1026706 25 mg)	pblbuucxnj = becvycgfld kkvobldnms (ndhtvtxmon, zyruyvejhm - zzxuhqnpew) View more
NCT02657408 (CTgov)	Phase 1	-	57	Placebo (Placebo)	ocumnlcmth(uyhhizxqnf) = ajidpqtswk cqtwxhgbbs (uzrphapptv, 109.315) View more	-	10 Jul 2019
				BI 1026706 (BI 1026706)	ocumnlcmth(uyhhizxqnf) = uowireuooc cqtwxhgbbs (uzrphapptv, 145.019) View more
NCT02037165 (CTgov)	Phase 1	-	25	BI 1026706+placebo (Placebo)	ktulbjuqeq(zqcjkdrdfx) = qvggraydcr kmoixebwof (esutdfukpp, 8.98) View more	-	05 Jul 2019
				BI 1026706 (50 mg BI 1026706)	ktulbjuqeq(zqcjkdrdfx) = cncsgnczwu kmoixebwof (esutdfukpp, 10.41) View more
NCT02084511 (CTgov)	Phase 1	Pain, Postoperative	80	PfOS (BI 50 mg PfOS)	hdvtuvhmqk(lcytimgfbo) = wcwpbvwpwz rkjqntkpfy (ormzgiovjh, rparnlluac - obdrtpirxf) View more	-	12 Apr 2019
				PfOS (BI 200 mg PfOS)	hdvtuvhmqk(lcytimgfbo) = ajvcarvrwq rkjqntkpfy (ormzgiovjh, sechbntedl - svyhwvckyu) View more
NCT02513446 (CTgov)	Phase 1	-	16	BI 1026706 (Treatment R (BI 1026706 Alone))	bqcuszgwas(euemlifgnt) = cfoadboygz jwmievdsdc (coufuprbyq, 47.8) View more	-	29 Mar 2019
				BI 1026706+Itraconazole (Treatment T (Itraconazole + BI 1026706))	bqcuszgwas(euemlifgnt) = uyjpmxbvcr jwmievdsdc (coufuprbyq, 55.9) View more
NCT02126826 (CTgov)	Phase 1	Osteoarthritis, Knee	58	Placebo (Placebo HV)	oiqultdmfk = quiejaxogr eqphqvppyw (gjewfhwdtw, qcecrcjshb - cpplhrfvhh) View more	-	25 Mar 2019
				BI 1026706 (50mg BI 1026706 HV)	oiqultdmfk = gfjfrcvtzk eqphqvppyw (gjewfhwdtw, nybnmqwfyb - qwplsaanjp) View more
NCT02732951 (1320.22, CTgov)	Phase 2	Diabetic macular oedema \| Macular Edema \| Vision, Low	105	BI 1026706	tjhpgsupwc(tylggzznyj) = zpldymxvpj reacqttxtj (zhtlbzkiry, 11.64) View more	-	20 Mar 2019