Last update 21 Jun 2024
Danegaptide hydrochloride
Last update 21 Jun 2024
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms Danegaptide, GAP-Oral, GAP-134 + [2] |
Target |
Mechanism GJs modulators(Gap junction proteins modulators), Immunostimulants |
Therapeutic Areas |
Active Indication |
Inactive Indication |
Originator Organization |
Active Organization |
Inactive Organization |
Drug Highest PhasePhase 1/2 |
First Approval Date- |
Regulation- |
Structure
Molecular FormulaC14H18ClN3O4 |
InChIKeyAHXPMNACLWKFRQ-DHXVBOOMSA-N |
CAS Registry943133-81-1 |
Related
5
Clinical Trials associated with Danegaptide hydrochlorideA Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Assess Clinical Efficacy and Safety of Danegaptide in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
This study explores the potential cardioprotective properties of danegaptide when administered to patients with ST-Segment elevation myocardial infarction.
Start Date01 Nov 2013 |
Sponsor / Collaborator |
A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Assess Clinical Efficacy and Safety of Danegaptide in Patients with ST-Elevation Myocardial Infarction undergoing Primary Percutaneous Coronary Intervention
Start Date14 Aug 2013 |
Sponsor / Collaborator |
An Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of GAP-134 Administered Intravenously as 6-Day Continuous Infusions to Healthy Subjects
This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending doses of GAP 134 administered as 6-day continuous IV infusions to healthy subjects.
Start Date01 Nov 2008 |
Sponsor / Collaborator |
100 Clinical Results associated with Danegaptide hydrochloride
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100 Translational Medicine associated with Danegaptide hydrochloride
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100 Patents (Medical) associated with Danegaptide hydrochloride
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31
Literatures (Medical) associated with Danegaptide hydrochloride31 Dec 2023·Journal of the International Society of Sports Nutrition
Beneficial effects of oral and topical sodium bicarbonate during a battery of team sport-specific exercise tests in recreationally trained male athletes
Article
Author: Ranchordas, Mayur K ; Gurton, William H ; Chudzikiewicz, Karolina ; Greally, Jordanne ; Lynn, Anthony ; Gough, Lewis A
OBJECTIVE:
This study examined the effects of oral and topical (PR Lotion; Momentous) sodium bicarbonate (NaHCO3) during a battery of team sport-specific exercise tests.
METHOD:
In a block randomized, crossover, double-blind, placebo-controlled design, 14 recreationally trained male team sport athletes performed a familiarization visit and three experimental trials receiving: (i) 0.3 g·kg-1 body mass (BM) NaHCO3 in capsules + placebo lotion (SB-ORAL), (ii) placebo capsules +0.9036 g·kg-1 BM PR Lotion (SB-LOTION), or (iii) placebo capsules + placebo lotion (PLA). Supplements were given ~120 min prior to the team sport-specific exercise tests: countermovement jumps (CMJ), 8 × 25 m repeated sprints and Yo-Yo Intermittent Recovery Level 2 (Yo-Yo IR2). Blood acid-base balance (pH, bicarbonate) and electrolytes (sodium, potassium) were measured throughout. Rating of perceived exertion (RPE) was recorded after each sprint and post-Yo-Yo IR2.
RESULTS:
Distance covered during the Yo-Yo IR2 was 21% greater for SB-ORAL compared with PLA (+94 m; p = 0.009, d = 0.64) whereas performance was only 7% greater for SB-LOTION compared with PLA (480 ± 122 vs. 449 ± 110 m; p = 0.084). Total completion time for the 8 × 25 m repeated sprint test was 1.9% faster for SB-ORAL compared with PLA (-0.61 s; p = 0.020, d = 0.38) and 2.0% faster for SB-LOTION compared with PLA (-0.64 s; p = 0.036, d = 0.34). CMJ performance was similar between treatments (p > 0.05). Blood acid-base balance and electrolytes were significantly improved for SB-ORAL compared with PLA, but no differences were observed for SB-LOTION. Compared to PLA, RPE was lower for SB-LOTION after the fifth (p = 0.036), sixth (p = 0.012), and eighth (p = 0.040) sprints and for SB-ORAL after the sixth (p = 0.039) sprint.
CONCLUSIONS:
Oral NaHCO3 improved 8 × 25 m repeated sprint (~2%) and Yo-Yo IR2 performance (21%). Similar improvements in repeated sprint times were observed for topical NaHCO3 (~2%), but no significant benefits were reported for Yo-Yo IR2 distance or blood acid-base balance compared to PLA. These findings suggest that PR Lotion might not be an effective delivery system for transporting NaHCO3 molecules across the skin and into systematic circulation, therefore further research is needed to elucidate the physiological mechanisms responsible for the ergogenic effects of PR Lotion.
01 Apr 2023·American journal of hematology
Long‐term survival with oral azacitidine for patients with acute myeloid leukemia in first remission after chemotherapy: Updated results from the randomized, placebo‐controlled, phase 3 QUAZAR AML ‐001 trial
Letter
Author: Jang, Jun‐Ho ; See, Wendy L. ; Menezes, Daniel ; Beach, C. L. ; Sayar, Hamid ; Wei, Andrew H. ; Porkka, Kimmo ; Selleslag, Dominik ; Dombret, Hervé ; Skikne, Barry ; Roboz, Gail J. ; Risueño, Alberto ; Montesinos, Pau ; Ugidos, Manuel ; Döhner, Hartmut ; Ravandi, Farhad ; Zhang, George ; Prebet, Thomas
Despite recent therapeutic advances, outcomes remain poor for older patients with acute myeloid leukemia (AML).For patients in the USA diagnosed with AML between 2010 - 2017, the 5-yr overall survival (OS) rate was 22% for patients aged 60 - 69 years, and only 5% for those aged ≥ 70 years.Survival outcomes are influenced by patient- and disease-related factors, including age, comorbidities, cytogenetic abnormalities, gene mutations, and persistence of leukemic cells after intensive chemotherapy (IC) (i.e., measurable residual disease [MRD]).There is a need for effective maintenance therapies to prolong survival among HSCT-ineligible patients in complete remission.In the randomized, double-blind, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) significantly prolonged OS and relapse-free survival (RFS) vs. placebo in patients ≥ 55 years with AML in first remission after IC who were not HSCT candidates.Here, we present updated OS outcomes (data cutoff March 2022) with the median follow-up time now 55.5 mo and investigate clin. and biol. variables predictive of long-term survival, defined here as survival ≥ 3 years from randomization, in patients treated with Oral-AZA or placebo.Briefly, patients aged ≥ 55 years with intermediate-or poor-risk cytogenetics at diagnosis who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) with IC, were randomized 1:1 to receive Oral-AZA 300-mg or placebo once-daily for 14 days in repeated 28-day cycles.OS was estimated by Kaplan-Meier methods and compared between treatment groups by stratified log-rank test. NPM1 and FLT3 gene mutations (mut) were assessed locally at diagnosis for most patients; post-IC MRD status was assessed centrally at study screening by multiparameter flow cytometry.Estimated 3-yr survival rates in the Oral-AZA and placebo arms were 37.4% and 27.9%, resp. ( Δ + 9.5% with Oral-AZA [95%CI + 0.9% to + 18.1%]); 5-yr survival rates were 26.5% vs. 20.1% ( Δ + 6.3% [95%CI 2.1% to + 14.7%]).The model included randomized treatment arm (Oral-AZA vs. placebo), NPM1 status ( NPM1 mut vs. NPM1 wt ) at diagnosis, cytogenetic risk (poor vs. intermediate) at diagnosis, MRD status (MRD + vs. MRD - )at screening, and absolute neutrophil count (continuous variable) at screening.In conclusion, these updated findings demonstrate the feasibility and sustained long-term clin. benefit of Oral-AZA maintenance, now with over 4 years of median follow-up time for patients in remission after chemotherapy.Patients with AML completing intensive induction and consolidation therapy should therefore be strongly considered for Oral-AZA maintenance, particularly those for whom HSCT may not be feasible or initially indicated, including patients with favorable risk NPM1 mutated disease.
30 Mar 2023·Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction
Article
Author: Tilsted, Hans-Henrik ; Jøns, Christian ; Atharovski, Kiril ; Nepper-Christensen, Lars ; Bertelsen, Litten ; Jacobsen, Peter Karl ; Engstrøm, Thomas ; Lønborg, Jacob ; Thomsen, Anna F ; Vejlstrup, Niels ; Kyhl, Kasper ; Køber, Lars ; Ekström, Kathrine ; Jabbari, Reza ; Göransson, Christoffer ; Pedersen, Frants
Abstract:
Aims:
Late gadolinium enhancement cardiac magnetic resonance (CMR) permits characterization of left ventricular ischaemic scars. We aimed to evaluate if scar core mass, border zone (BZ) mass, and BZ channels are risk markers for subsequent ventricular arrhythmia (VA) in ST-segment elevation myocardial infarction (STEMI).
Methods and results:
A sub-study of the DANish Acute Myocardial Infarction-3 multi-centre trial and Danegaptide phase II proof-of-concept clinical trial in which a total of 843 STEMI patients had a 3-month follow-up CMR. Of these, 21 patients subsequently experienced VA during 100 months of follow-up and were randomly matched 1:5 with 105 controls. A VA event was defined as: ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. Ischaemic scar characteristics were automatically detected by specialized software. We included 126 patients with a median left ventricular ejection fraction of 51.0 ± 11.6% in cases with VA vs. 55.5 ± 8.5% in controls (P = 0.10). Cases had a larger mean BZ mass and more often BZ channels compared to controls [BZ mass: 17.2 ± 10.3 g vs. 10.3 ± 6.0 g; P = 0.0002; BZ channels: 17 (80%) vs. 44 (42%); P = 0.001]. A combination of ≥17.2 g BZ mass and the presence of BZ channels was five times more prevalent in cases vs. controls (P ≤ 0.00001) with an odds ratio of 9.40 (95% confidence interval 3.26–27.13; P ≤ 0.0001) for VA. This identified cases with 52% sensitivity and 90% specificity.
Conclusion(s):
Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients.
ClinicalTrials.gov:
Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER), NCT01960933 (DANAMI 3-PRIMULTI), and NCT01977755 (Danegaptide).
4
News (Medical) associated with Danegaptide hydrochloride25 Jan 2024
Investigating potential for an oral treatment in diabetic retinopathy
First patient dosed in Phase 1b/2a clinical trial
COPENHAGEN, Denmark, Jan. 25, 2024 /PRNewswire/ -- Breye Therapeutics ApS (Breye), a clinical-stage biopharmaceutical company developing novel oral therapies for retinal vascular diseases within ophthalmology, today announces the start of a phase 1b/2a clinical trial to investigate danegaptide, following oral administration, in patients suffering from diabetic macular edema (DME).
Breye is developing novel, oral ophthalmology drugs to address the need for more effective and less burdensome therapies for millions of patients suffering with deteriorating vision due to Diabetic Retinopathy (DR) or Age-Related Macular Degeneration (AMD). While there has been successful development of intravitreally administered products for patients with late-stage disease, treatment options are currently limited for patients in the early or moderate stages.
As an oral therapy, danegaptide targets the core pathological events in DR, including cell-cell uncoupling, apoptotic vascular cell death and vascular leakage, at earlier stages of disease progression.
With safety data derived from over 500 clinical trial participants, robust toxicology data, and strong non-clinical in vitro and in vivo efficacy results, there is strong support for danegaptide's potential to address the clinical core ocular pathologies of vascular leakage and capillary breakdown. The positive effects of treating these pathologies have been clinically validated.
The study's design is a multicenter, open-label, dose-escalating Phase 1b/2a study to assess the safety, tolerability, pharmacokinetics (PK), and early signs of biological activity following oral administration of danegaptide in participants diagnosed with DME.
Ulrik Mouritzen, Chief Executive Officer of Breye Therapeutics, said: "The launch of the Phase 1b/2a clinical trial for danegaptide represents a significant milestone towards realising our mission of developing more effective, globally accessible orally administered treatment solutions for patients at risk of vision loss and blindness. The burden on patients with diabetic retinopathy is significant and those who experience vision loss and blindness face threats to their physical and mental health and overall quality of life. At Breye, we are committed to help treat the disease earlier by offering effective oral therapies, to patients who currently have limited or no treatment options."
Prof. Carl Regillo, MD, Director of Retina Service of Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University in Philadelphia, Member of the Breye Therapeutics Scientific Advisory Board, commented: "Danegaptide has the potential to become a valuable oral treatment option for patients with Diabetic Retinopathy. Patients should ideally be treated earlier and before the disease progresses to later stages, where laser treatments or intravitreally administered products are required."
About Breye Therapeutics
Breye is a biopharmaceutical company developing novel, oral ophthalmology drugs to address the needs of millions of patients suffering with deteriorating vision due to Diabetic Retinopathy (DR) or Age-Related Macular Degeneration (AMD), for which there are no treatments in early or moderate disease. Severe diabetic retinopathy requires intravitreal injections directly into the eye, which are unpopular with patients, resulting in a significant drop out rate of about 50% after 1 year and only 40% of patients obtain an optimal response. Orally administered drugs will be less burdensome than injections, as well as potentially more effective and commercially competitive. With its clinically de-risked safety profile, the lead program with danegaptide has potential for a short and well-accepted clinical regulatory pathway. Breye is also developing an oral P2X7R antagonist for AMD which seeks to reduce nerve damage and inflammation.
Breye raised a seed round from Novo Holdings and Sound BioVentures and received financial support from the BioInnovation Institute, the Danish Growth Foundation (Vækstfonden) and the Danish Innovation Foundation (Innovationsfonden).
For more information, please visit:
SOURCE Breye Therapeutics
Clinical Study
25 Jul 2023
Collaboration to advance development of innovative oral small molecule therapeutics for retinal disorders
MILAN and COPENHAGEN, Denmark, July 25, 2023 /PRNewswire/ -- Golgi Neurosciences S.r.l., the biotech incubator dedicated to the development of new treatments for devastating diseases, and Breye Therapeutics ApS, a clinical-stage biopharmaceutical company developing novel oral therapies for retinal vascular diseases, today announces a collaboration to develop the P2X7 receptor antagonist programme.
The P2X7 receptor is an ATP-gated ion channel expressed in various cell types and is a key inflammation switch. Inflammation increases in the diabetic retina and does so in a self-propagating manner. Strong scientific evidence also implicates inflammation in the pathogenesis of AMD. Orally available antagonists of the P2X7 receptor represent a novel approach for the treatment of both early-stage DR and dry-AMD.
Diabetic Retinopathy (DR) affects 30% of diabetic patients and is one of the leading causes of blindness among working age adults. Age-Related Macular Degeneration (AMD) is another prominent cause of vision loss, particularly for individuals aged 60 years and older.
Chiara Liberati, Managing Director, Golgi Neurosciences, commented: "There is a significant need for more effective and patient-compliant drugs in the ophthalmic field. With leading experts on the Scientific Advisory Board, Breye is led by a strong and seasoned Management team, supported by a highly-regarded syndicate of investors, making Breye the ideal partner to facilitate the next steps in advancing our P2X7 receptor antagonist program towards developing innovative approaches for retinal disorders.
"This marks the first closed deal for Golgi Neurosciences since its inception which serves as a validation for the quality of our research in the field of small-molecule drugs."
Ulrik Mouritzen
, Chief Executive Officer, Breye Therapeutics, said: "The Golgi incubator has fantastic expertise in neurosciences, and we are pleased to collaborate to advance the P2X7 receptor antagonist program for retinal disorders, where there is a large unmet medical need for more effective and less burdensome therapies."
About Golgi Neurosciences
Golgi Neurosciences is a biotech incubator based in Milan, Italy, dedicated to the discovery and development of small molecule-based treatments for neurodegenerative diseases with high unmet need. The incubator boasts a diverse portfolio of clinical and preclinical stage companies, all focused on programs targeting various neurodegenerative diseases, including Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, Multiple Sclerosis and Retinopathies. In addition, Golgi Neurosciences is progressing a robust pipeline of proprietary projects on innovative therapeutics targets, for which it is open to partnership.
For more information, please visit: golgineurosciences.com
About Breye Therapeutics
Breye is a biopharmaceutical company developing novel, oral ophthalmology drugs to address the needs of millions of patients suffering with deteriorating vision due to Diabetic Retinopathy (DR) or Age-Related Macular Degeneration (AMD), for which there are no treatments in early or moderate disease. Severe diabetic retinopathy requires intravitreal injections directly into the eye, which are unpopular with patients, resulting in a significant drop out rate of about 50% after 1 year and only 40% of patients obtain an optimal response. Orally administered drugs will be less burdensome than injections, as well as potentially more effective and commercially competitive. With its clinically de-risked safety profile, the lead program with danegaptide has potential for a short and well-accepted clinical regulatory pathway. The addition of the oral P2X7R inhibitor program seeks to reduce nerve damage and inflammation in retinal diseases.
Breye raised a seed round from Novo Holdings and Sound BioVentures and received financial support from the BioInnovation Institute, the Danish Growth Foundation (Vækstfonden) and the Danish Innovation Foundation (Innovationsfonden).
For more information, please visit:
SOURCE Golgi Neurosciences; Breye Therapeutics
21 Apr 2023
Industry veteran Dr. Peter Adamson, PhD appointed as Chief Scientific Officer
Dr. Gabriela Burian, MD appointed to the Board of Directors
COPENHAGEN, Denmark , April 20, 2023 /PRNewswire/ -- Breye Therapeutics ApS (Breye), a clinical-stage biopharmaceutical company developing novel oral therapies for retinal vascular diseases within ophthalmology, today announces the appointment of Peter Adamson as Chief Scientific Officer (CSO) and Gabriela Burian as a new member of its Board of Directors.
Dr. Adamson has over 20 years of experience in ophthalmology drug development. He has previously held senior leadership positions at various biopharmaceutical companies including Vice President and Head of Ophthalmology Research at GlaxoSmithKline, where he generated multiple clinical candidates and acted as Lead Biologist on a number of discovery programmes. He previously also worked at ProQR and recently Tenpoint Therapeutics, where he was involved in building pipelines and securing successful financing.
Gabriela Burian is a physician-scientist with over 25 years of experience in clinical research and drug development in ophthalmology. She has held various global leadership positions at leading biopharmaceutical companies including Roche and Novartis.
Breye is developing novel, oral ophthalmology drugs to address the needs of millions of patients suffering with deteriorating vision due to Diabetic Retinopathy (DR) or Age-Related Macular Degeneration (AMD), for which there are no broadly available treatments in early or moderate disease. It is focused on advancing into clinic its lead compound to phase 1b.
Ulrik Mouritzen, CEO of Breye Therapeutics, said: "We are thrilled to welcome Peter as CSO. His extensive experience in ophthalmology drug development will be invaluable as we advance our lead compound through clinical development. Gabriela's appointment to the Board brings significant industry and development experience which will be instrumental as we build a pipeline of novel oral therapies for retinal vascular diseases within ophthalmology."
Peter Adamson, CSO of Breye Therapeutics, commented: "I am pleased to join the team at Breye Therapeutics and to drive the development of our pipeline of innovative oral therapies for retinal vascular diseases and bring much needed treatments to patients."
Gabriela Burian, newly appointed Board Member of Breye Therapeutics, said: "I am honoured to join the Board of Directors and to support the management team in its goal to develop first-in-class oral drugs for treating Diabetic Retinopathy and Age-Related Macular Degeneration and broaden the access to therapeutic options in this patient population."
About Breye Therapeutics
Breye is a biopharmaceutical company developing novel, oral ophthalmology drugs to address the needs of millions of patients suffering with deteriorating vision due to Diabetic Retinopathy (DR) or Age-Related Macular Degeneration (AMD), for which there are no treatments in early or moderate disease. Danegaptide is an oral investigational compound that targets diabetic retinopathy, a serious complication of a rapidly growing global disease. Severe diabetic retinopathy requires intravitreal injections directly into the eye, which are unpopular with patients, resulting in a significant drop out rate of about 50% after 1 year and only 40% of patients obtain an optimal response. Originally developed for cardiac indications, clinical studies have shown danegaptide to be a safe drug, stabilising cell-cell coupling and protecting against vascular leakage and capillary breakdown. Danegaptide is orally administered and less burdensome than injections, as well as potentially more effective and commercially competitive. With its recognised safety profile, danegaptide has potential for a short and well accepted clinical regulatory pathway. Breye is also developing an oral P2X7R inhibitor for AMD which seeks to reduce nerve damage and inflammation.
Breye raised a seed round from Novo Holdings and Sound BioVentures and received financial support from the BioInnovation Institute, the Danish Growth Foundation (Vækstfonden) and the Danish Innovation Foundation (Innovationsfonden).
For more information, please visit:
SOURCE Breye Therapeutics
Executive Change
100 Deals associated with Danegaptide hydrochloride
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External Link
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R&D Status
10 top R&D records. to view more data
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| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Diabetic macular oedema | Phase 2 | - | 25 Jan 2024 | |
| ST Elevation Myocardial Infarction | Phase 2 | DK | 01 Nov 2013 | |
| Wet age-related macular degeneration | Phase 1 | US | - |
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Clinical Result
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| Study | Phase | Population | Analyzed Enrollment | Group | Results | Evaluation | Publication Date |
|---|
Phase 2 | 585 | mltaxigwvs(lrdhpbssbo) = couddvfzwo gcxzrwhsko (euecyubysr ) | - | 01 Oct 2018 | |||
mltaxigwvs(lrdhpbssbo) = svheihozik gcxzrwhsko (euecyubysr ) |
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