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29 Diseases |  |
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1 Trial |  |
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- | varespladib (A-002) / Anthera Pharma, Ophirex
Preclinical, Journal: Role of Phospholipases A in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues. (Pubmed Central) - Nov 10, 2021
Based on their inhibition with the sPLA inhibitor varespladib, we conclude that PLA toxins in P. aspidorhyncha, P. nuchalis, and P. textilis venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of P. affinis, and P. textilis venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.
- | Tyrisa (darapladib) / GSK, varespladib (A-002) / Anthera Pharma, Ophirex
Journal: The design and discovery of phospholipase A inhibitors for the treatment of inflammatory diseases. (Pubmed Central) - Nov 6, 2021
A deeper understanding of PLA enzymes is needed for the development of novel selective inhibitors. Lipidomic technologies in combination with classical medicinal chemistry approaches may be useful tools towards this goal.
- | varespladib (A-002) / Anthera Pharma, Ophirex
Preclinical, Journal: Varespladib (LY315920) prevents neuromuscular blockage and myotoxicity induced by crotoxin on mouse neuromuscular preparations. (Pubmed Central) - Oct 22, 2021
Pre-incubation with Varespladib abolished the muscle-paralyzing activity of CTX and CB, and also the muscle-damaging activity of CTX. These findings emphasize the clinical potential of Varespladib in mitigating the toxic effects of C. d. terrificus snakebites and as a research tool to advance the knowledge of the mechanism of action of snake toxins.
- || Retrospective data, Review, Journal, HEOR: Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-Analysis. (Pubmed Central) - Sep 22, 2021
Although many anti-inflammatory medications have failed to reduce adverse cardiovascular outcomes in the CAD population, selected medications show promise among subgroups of patients without ACS or after the first week following an acute ischemic event. Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted.
- | varespladib (A-002) / Anthera Pharma, Ophirex
Journal: The synthetic Varespladib molecule is a multi-functional inhibitor for PLA and PLA-like ophidic toxins. (Pubmed Central) - Sep 11, 2021
Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted. Varespladib appears to be a promissory molecule in the treatment of local effects led by PLA and PLA-like toxins (oligomeric dependent and independent), indicating that this is a multifunctional or broadly specific inhibitor for different toxins within this superfamily.
- || varespladib (A-002) / Anthera Pharma, Ophirex
Clinical, Journal: Clinical management of snakebite envenoming: Future perspectives. (Pubmed Central) - Aug 26, 2021
Repurposed pharmaceuticals based on small molecule inhibitors (e.g., marimastat and varespladib) used alone and in combination against enzymatic toxins, such as metalloproteases and phospholipase As, have shown promise in animal studies...Antivenom access can be improved by the usage of drones and ensuring constant antivenom supply in remote endemic rural areas. Overall, the improvement of clinical management of snakebite envenoming requires sustained, coordinated, and multifaceted efforts involving basic and applied sciences, new technology, product development, effective clinical training, implementation of existing guidelines and therapeutic approaches, supported by improved supply of existing antivenoms.
- |||| varespladib (A-002) / Anthera Pharma, Ophirex
New P2 trial: BRAVO: Broad-spectrum Rapid Antidote: Varespladib Oral for Snakebite (clinicaltrials.gov) - Aug 8, 2021
P2, N=110, Recruiting, Sponsor: Ophirex, Inc.
- | Tyrisa (darapladib) / GSK, varespladib (A-002) / Anthera Pharma, Ophirex
Journal: On the present and future role of Lp-PLA in atherosclerosis-related cardiovascular risk prediction and management. (Pubmed Central) - Aug 3, 2021
This gives us a strong imperative to continue research aimed at a better understanding of how Lp-PLA and sPLA regulate vascular inflammation and atherosclerotic plaque development. From the clinical viewpoint there is a need to establish and validate the existing and emerging novel anti-inflammatory therapeutic strategies to fight against ASCVD development, by using potentially better animal models and differently designed clinical trials in humans.
- | varespladib (A-002) / Anthera Pharma, Ophirex
New P2 trial: STAIRS: Study of Varespladib in Patients Hospitalized With Severe COVID-19 (clinicaltrials.gov) - Jul 20, 2021
P2, N=90, Recruiting, Sponsor: Ophirex, Inc.
- | varespladib (A-002) / Anthera
Journal: Anticoagulant Activity of Naja nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib. (Pubmed Central) - Jul 4, 2021
Varespladib, but not marimastat, was found to significantly reduce the anticoagulant activity of N. nigricollis venom and MS and proteomics analyses confirmed that the anticoagulant venom components mostly consisted of PLA proteins. We, therefore, conclude that PLAs are the most likely candidates responsible for anticoagulant effects stimulated by N. nigricollis venom.
- | varespladib (A-002) / Anthera
Preclinical, Journal: Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A activity with varespladib. (Pubmed Central) - Jun 22, 2021
Varespladib might be used as a first-aid therapeutic against P. mucrosquamatus envenoming in the pre-referral period and/or as an adjunctive agent administered together with anti-P. mucrosquamatus antivenom.
- | varespladib (A-002) / Anthera
Journal: Fluorescent Lipo-Beads for the Sensitive Detection of Phospholipase A and Its Inhibitors. (Pubmed Central) - May 15, 2021
We find that quercetin can hydrolyze the supported membrane, and thus inhibition of PLA is not observed; however, varespladib has shown significant PLA inhibition on lipo-beads. We have demonstrated that our lipo-bead-based approach can detect annexin-3, a known disease biomarker, as low as 10 nM within 5 min after incubation.
- || varespladib (A-002) / Anthera
Review, Journal: Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A. (Pubmed Central) - Mar 20, 2021
This review is comprehensive and covers the most recent developments in the understanding of the many facets of hGIIA function and inhibition and the insight they provide into their clinical application for disease treatment. A cyclic analogue of FLSYK, c2, the most potent analogue known, has now been taken into clinical trials targeting advanced prostate cancer.
- | varespladib (A-002) / Anthera
Journal: PLA Inhibitor Varespladib as an Alternative to the Antivenom Treatment for Bites from Nikolsky's Viper Vipera berus nikolskii. (Pubmed Central) - Mar 4, 2021
Eighty percent of mice receiving both Varespladib and venom survived, while 100% of the control group receiving venom alone died within 4 h. Experimental results are consistent with Varespladib acting as an effective antitoxin in the mouse model against Nikolsky's viper venom. Further studies are needed under experimental conditions that more closely resemble natural envenoming (i.e., delayed administration).
- | varespladib (A-002) / Anthera
Journal: Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. (Pubmed Central) - Feb 23, 2021
Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLAs. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine.
- | varespladib (A-002) / Anthera
Journal: Varespladib (LY315920) neutralises phospholipase A mediated prothrombinase-inhibition induced by Bitis snake venoms. (Pubmed Central) - Feb 20, 2021
Our results demonstrate that varespladib strongly neutralises the prothrombinase-inhibiting effects of all venoms tested in this study, and that this prothrombinase-inhibiting mechanism of anticoagulant activity is driven by phospholipase A class toxins in these four species. This study extends previous reports demonstrating varespladib has broad efficacy for treatment of phospholipase A rich snake venoms, indicating it also inhibits their anticoagulant effects mediated by prothrombinase-inhibition.
- | quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University, varespladib (A-002) / Anthera
Journal: NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria. (Pubmed Central) - Feb 20, 2021
However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.
- | varespladib (A-002) / Anthera
Journal: Toxinological characterization of venom from Leptodeira annulata (Banded cat-eyed snake; Dipsadidae, Imantodini). (Pubmed Central) - Jan 15, 2021
The venom had phospholipase A (PLA) activity that was inhibited by varespladib...In gastrocnemius muscle, the venom caused myonecrosis and increased serum creatine kinase concentrations. In conclusion, L. annulata venom has various enzymatic and biological activities, with the local effects being mediated primarily by metalloproteinases and PLA.
- | varespladib (A-002) / Anthera
Journal: Anticoagulant Micrurus venoms: targets and neutralization. (Pubmed Central) - Jan 12, 2021
This is consistent with the growing body of results showing that varespladib may be an effective treatment for a wide range of toxicity caused by PLA toxins from many different snake species. Varespladib is a particularly attractive candidate to help alleviate the burden of snakebite because it is an approved drug that possesses several logistical advantages over antivenom including temperature stability and oral availability.
- | varespladib (A-002) / Anthera
Preclinical, Journal: A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. (Pubmed Central) - Jan 5, 2021
Furthermore, using murine in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents murine lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings support the translation of combinations of repurposed small molecule-based toxin inhibitors as broad-spectrum therapeutics for snakebite.
- varespladib (A-002) / Anthera Pharma, Ophirex
Trial termination: IMPACTS-2: A Study of Varespladib Infusion in Subjects With Sickle Cell Disease. (clinicaltrials.gov) - Mar 20, 2012
P2, N=2, Terminated, Sponsor: Anthera Pharmaceuticals
Our findings support the translation of combinations of repurposed small molecule-based toxin inhibitors as broad-spectrum therapeutics for snakebite. Not yet recruiting --> Terminated; change in company plans
- varespladib (A-002) / Anthera Pharma, Ophirex
Enrollment change: IMPACTS-2: A Study of Varespladib Infusion in Subjects With Sickle Cell Disease. (clinicaltrials.gov) - Mar 20, 2012
P2, N=2, Terminated, Sponsor: Anthera Pharmaceuticals
Not yet recruiting --> Terminated; change in company plans N=150 --> 2
- varespladib (A-002) / Anthera Pharma, Ophirex
Trial termination: A Study of the Pharmacokinetics and Safety of Varespladib in Subjects With Normal or Impaired Renal Function (clinicaltrials.gov) - Mar 18, 2012
P1, N=28, Terminated, Sponsor: Anthera Pharmaceuticals
N=150 --> 2 Recruiting --> Terminated; Lack of efficacy
- | varespladib (A-002) / Anthera Pharma, Ophirex
Trial termination: VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome (clinicaltrials.gov) - Mar 18, 2012
P3, N=5189, Terminated, Sponsor: Anthera Pharmaceuticals
Recruiting --> Terminated; Lack of efficacy Recruiting --> Terminated; Lack of efficacy
- varespladib (A-002) / Anthera Pharma, Ophirex
Enrollment change: A Study of the Pharmacokinetics and Safety of Varespladib in Subjects With Normal or Impaired Renal Function (clinicaltrials.gov) - Mar 18, 2012
P1, N=28, Terminated, Sponsor: Anthera Pharmaceuticals
Recruiting --> Terminated; Lack of efficacy N=36 --> 28
- | varespladib (A-002) / Anthera Pharma, Ophirex
Enrollment change: VISTA-16 Trial: Evaluation of Safety and Efficacy of Short-term A-002 Treatment in Subjects With Acute Coronary Syndrome (clinicaltrials.gov) - Mar 18, 2012
P3, N=5189, Terminated, Sponsor: Anthera Pharmaceuticals
N=36 --> 28 N=6500 --> 5189
- varespladib (A-002) / Anthera Pharma, Ophirex
New P2 trial: IMPACTS-2: A Study of Varespladib Infusion in Subjects With Sickle Cell Disease. (clinicaltrials.gov) - Jan 29, 2012
P2, N=2, Terminated, Sponsor: Anthera Pharmaceuticals
- | varespladib (A-002) / Anthera Pharma, Ophirex
Enrollment change: IMPACTS Trial: Investigation of the Modulation of Phospholipase in Acute Chest Syndrome (clinicaltrials.gov) - Jan 17, 2012
P2, N=30, Completed, Sponsor: Anthera Pharmaceuticals
N=6500 --> 5189 N=60 --> 30
- varespladib (A-002) / Anthera Pharma, Ophirex
Trial completion: Study to Assess the Metabolism and Elimination of [14C]-Labeled Varespladib Methyl in Healthy Male Subjects (clinicaltrials.gov) - Oct 18, 2011
P1, N=6, Completed, Sponsor: Anthera Pharmaceuticals
N=60 --> 30 Active, not recruiting --> Completed