CONNECTS Master Protocol for Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular Hyperinflammation, and Hypercoagulability and Renin-angiotensin-aldosterone System (RAAS) in Hospitalized Patients With COVID-19 (ACTIV-4 Host Tissue)

The overarching goal of the Master Protocol is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19. The primary analysis will include data from NCT05593770.

Start Date15 Jul 2021

Sponsor / Collaborator

Vanderbilt University Medical Center

[+2]

NCT04419610

/ CompletedEarly Phase 1IIT

Investigating the Relationship Between the Renin Angiotensin System and the Coagulopathy Associated With COVID-19

To determine whether the coagulopathy associated with COVID-19 infection is driven by overactivation of the renin angiotensin system (RAS)

Start Date09 Oct 2020

Sponsor / Collaborator

Imperial College London

EUCTR2013-002893-35-BG

/ Not yet recruitingPhase 2

A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure

Start Date15 Jan 2014

Sponsor / Collaborator

Trevena, Inc.

100 Clinical Results associated with TRV-120027

100 Translational Medicine associated with TRV-120027

100 Patents (Medical) associated with TRV-120027

Literatures (Medical) associated with TRV-120027

01 Dec 2024·Cellular Signalling

Implications of β-Arrestin biased signaling by angiotensin II type 1 receptor for cardiovascular drug discovery and therapeutics

Review

Author: Karnik, Sadashiva S ; Singh, Khuraijam Dhanachandra ; Karnik, Sadashiva S.

Angiotensin II receptors, Type 1 (AT1R) and Type 2 (AT2R) are 7TM receptors that play critical roles in both the physiological and pathophysiological regulation of the cardiovascular system. While AT1R blockers (ARBs) have proven beneficial in managing cardiac, vascular and renal maladies they cannot completely halt and reverse the progression of pathologies. Numerous experimental and animal studies have demonstrated that β-arrestin biased AT1R-ligands (such as SII-AngII, S1I8, TRV023, and TRV027) offer cardiovascular benefits by blocking the G protein signaling while retaining the β-arrestin signaling. However, these ligands failed to show improvement in heart-failure outcome over the placebo in a phase IIb clinical trial. One major limitation of current β-arrestin biased AT1R-ligands is that they are peptides with short half-lives, limiting their long-term efficacy in patients. Additionally, β-arrestin biased AT1R-ligand peptides, may inadvertently block AT2R, a promiscuous receptor, potentially negating its beneficial effects in post-myocardial infarction (MI) patients. Therefore, developing a small molecule β-arrestin biased AT1R-ligand with a longer half-life and specificity to AT1R could be more effective in treating heart failure. This approach has the potential to revolutionize the treatment of cardiovascular diseases by offering more sustained and targeted therapeutic effects.

28 Nov 2024·Journal of Medicinal Chemistry

Synthesis and Pharmacological Characterization of Fluorescent Ligands Targeting the Angiotensin II Receptors Derived from Agonists, β-Arrestin-Biased Agonists, and Antagonists

Article

Author: Acherar, Samir ; Colin, Mélissa ; Delaitre, Céline ; Humbert, Nicolas ; Dias, André ; Robin, Philippe ; Martinez, Karen L. ; Lecat, Sandra ; Kleinclauss, Alexandra ; Dupuis, François ; Gilles, Nicolas ; Chmeis, Khawla ; Nguyen, Trung Minh ; Boisbrun, Michel ; Achard, Mathilde

Angiotensin II (AngII) regulates cerebral circulation and binds with a similar affinity to AT₁ and AT₂ receptors. Biased AT₁ agonists, such as TRV027, which are able to selectively activate β-arrestin while blocking the G_q pathway, appear promising as new therapeutics. New pharmacological tools are needed to further explore the impact of biased AT₁ agonists on cells or tissues, such as the cerebral vessels. We designed and synthesized new fluorescent derivatives based on AngII, TRV027, or the AT₁ antagonist losartan. We conducted pharmacological characterization to determine their selectivity, potency, and ability to activate or not specific AT₁ transduction pathways in cells and cerebral arteries. We report the first highly AT₁-selective fluorescent ligand, based on losartan, that retains its antagonist activity with high affinity. Fluorescent derivatives of TRV027 become AT₂-selective and lose their AT₁ β-arrestin bias. These new ligands can be applied to trace AT₁ or AT₂ receptors in vitro and ex vivo.

22 Dec 2023·Clinical Science

β-Arrestin pathway activation by selective ATR1 agonism promotes calcium influx in podocytes, leading to glomerular damage

Article

Author: Ilatovskaya, Daria V ; Klemens, Christine A ; Solanki, Ashish K ; Cherezova, Alena ; Palygin, Oleg ; Hall, Gentzon ; Stefanenko, Mariia ; Marshall, Brendan ; Semenikhina, Marharyta ; Levchenko, Vladislav ; Staruschenko, Alexander ; Lipschutz, Joshua H ; Fedoriuk, Mykhailo

AbstractAngiotensin receptor blockers (ARBs) are the first-line treatment for hypertension; they act by inhibiting signaling through the angiotensin 1 receptor (AT1R). Recently, a novel biased AT1R agonist, TRV120027 (TRV), which selectively activates the β-arrestin cascade and blocks the G-protein-coupled receptor pathway has been proposed as a potential blood pressure medication. Here, we explored the effects of TRV and associated β-arrestin signaling in podocytes, essential cells of the kidney filter. We used human podocyte cell lines to determine β-arrestin’s involvement in calcium signaling and cytoskeletal reorganization and Dahl SS rats to investigate the chronic effects of TRV administration on glomerular health. Our experiments indicate that the TRV-activated β-arrestin pathway promotes the rapid elevation of intracellular Ca2+ in a dose-dependent manner. Interestingly, the amplitude of β-arrestin-mediated Ca2+ influx was significantly higher than the response to similar Ang II concentrations. Single-channel analyses show rapid activation of transient receptor potential canonical (TRPC) channels following acute TRV application. Furthermore, the pharmacological blockade of TRPC6 significantly attenuated the β-arrestin-mediated Ca2+ influx. Additionally, prolonged activation of the β-arrestin pathway in podocytes resulted in pathological actin cytoskeleton rearrangements, higher apoptotic cell markers, and augmented glomerular damage. TRV-activated β-arrestin signaling in podocytes may promote TRPC6 channel-mediated Ca2+ influx, foot process effacement, and apoptosis, possibly leading to severe defects in glomerular filtration barrier integrity and kidney health. Under these circumstances, the potential therapeutic application of TRV for hypertension treatment requires further investigation to assess the balance of the benefits versus possible deleterious effects and off-target damage.

News (Medical) associated with TRV-120027

30 Mar 2023

·www.prnewswire.com

Extremely Robust Acute Respiratory Distress Syndrome Pipeline Featuring 100+ Companies Expected to Change the Pace of the ARDS Treatment | DelveInsight

The rise in the incidence of ARDS stimulates the research and development of the drug, as it is likely to provide an appropriate environment for newer products to be profitable. Companies across the globe have shifted their focus toward the treatment of ARDS. The increase in the incidence will potentiate the treatment market for ARDS. Treatment goals, such as "permissive atelectasis", "permissive hypercapnia", and even "permissive hypoxemia", have been introduced as targets of ventilatory support. Together with the increased knowledge and understanding of how mechanical ventilation can harm the lungs, a major effort has been put into preventing or shortening the use of mechanical ventilation as much as possible and using settings that are considered to be "lung-protective." Several other supportive care options are available, but they all do not withstand the current needs of patients for this indication. LAS VEGAS, March 30, 2023 /PRNewswire/ -- DelveInsight's ' Acute Respiratory Distress Syndrome Pipeline Insight – 2023 ' report provides comprehensive global coverage of available, marketed, and pipeline acute respiratory distress syndrome therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the acute respiratory distress syndrome pipeline domain. Key Takeaways from the Acute Respiratory Distress Syndrome Pipeline Report DelveInsight's acute respiratory distress syndrome pipeline report depicts a robust space with 100+ active players working to develop 105+ pipeline therapies for acute respiratory distress syndrome treatment. Key acute respiratory distress syndrome companies such as Biocon, NRx Pharmaceuticals, Humanigen, Mesoblast, Sage Therapeutics, Evgen Pharma, Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Healthcare, Foresee Pharmaceuticals, BioMarck Pharmaceuticals, Boehringer Ingelheim, Biohaven Pharmaceuticals, Biophytis, NovImmune SA, Constant Therapeutics, Windtree Therapeutics, Acticor Biotech, Direct Biologics, F4 Pharma, Apeiron Biologics, Trevena, Synact Pharma, Pluristem Therapeutics, UCB Pharma, Chiesi Farmaceutici, and others are evaluating new acute respiratory distress syndrome drugs to improve the treatment landscape. Promising acute respiratory distress syndrome pipeline therapies in various stages of development include Itolizumab, ZYESAMI, Lenzilumab, Remestemcel-L, Brexanolone, SFX-01, DMX-200, Tradipitant, Siltuximab, VERU 111, BIO 11006, FP025, Alteplase, Sarconeos Zavegepant, EB 05, USB 002, Sinapultide, Glenzocimab, DB 001, FX06, APN01, TRV 027, AP1189, PLX PAD, Zilucoplan, CHF5633, and others. In March 2023, Tetra Bio-Pharma received up to $150,000 in funding from the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP) to support a research and development project to enable the development of its ARDS-003 oral formulation. Specifically, the funds will be used to optimize the formulation and perform animal non-GLP Pharmacokinetic Studies. In February 2021, Avid Bioservices and Humanigen announced that they had entered into a manufacturing services agreement to expand production capacity for lenzilumab. Under the terms of this Current Good Manufacturing Practice (cGMP) agreement, Avid would initiate technical transfer and analytical validation activities for lenzilumab with the goal of delivering cGMP drug substance batches to support Humanigen's regulatory and potential commercial activities. Request a sample and discover the recent advances in ARDS drug treatment @ Acute Respiratory Distress Syndrome Pipeline Report The acute respiratory distress syndrome pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage acute respiratory distress syndrome drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the acute respiratory distress syndrome clinical trial landscape. Acute Respiratory Distress Syndrome Overview Acute respiratory distress syndrome (ARDS) is a rapidly progressing condition that primarily affects the critically ill. The most serious complication of ARDS is fluid leaking into the lungs, making breathing difficult or impossible. The ARDS causes are classified as direct or indirect lung injuries. Direct lung injuries include pneumonia, aspiration, trauma, and others. Examples of indirect lung injuries include pancreatic inflammation, severe infection (also known as sepsis), blood transfusions, burns, and pharmaceutical responses. ARDS symptoms include shortness of breath, coughing, and fever; in some cases, high heart rates and rapid breathing have also been observed. Patients with ARDS may experience chest pain, especially during inhalation, and some may develop blue nails and lips due to drastically reduced oxygen levels in the blood. Mechanical ventilation, stress ulcer and venous thromboembolism prevention, nutritional support, and underlying damage therapy are all part of the acute respiratory distress syndrome treatment. Find out more about drugs for ARDS @ New Acute Respiratory Distress Syndrome Drugs A snapshot of the Acute Respiratory Distress Syndrome Pipeline Drugs mentioned in the report: Learn more about the emerging acute respiratory distress syndrome pipeline therapies @ ARDS Clinical Trials Acute Respiratory Distress Syndrome Therapeutics Assessment The acute respiratory distress syndrome pipeline report proffers an integral view of acute respiratory distress syndrome emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Acute Respiratory Distress Syndrome Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor antagonists, Hedgehog protein modulators, Histone deacetylase inhibitors, NF E2 related factor 2 stimulants, Wnt signalling pathway modulators, Cell replacements, Toll-like receptor 4 antagonists, Fibrinolytic agents, Plasminogen activator stimulants, Plasminogen activators, Myristoylated alanine-rich C kinase substrate inhibitors, Cell membrane permeability enhancers, Sodium channel agonists Key Acute Respiratory Distress Syndrome Companies: Biocon, NRx Pharmaceuticals, Humanigen, Mesoblast, Sage Therapeutics, Evgen Pharma, Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Healthcare, Foresee Pharmaceuticals, BioMarck Pharmaceuticals, Boehringer Ingelheim, Biohaven Pharmaceuticals, Biophytis, NovImmune SA, Constant Therapeutics, Windtree Therapeutics, Acticor Biotech, Direct Biologics, F4 Pharma, Apeiron Biologics, Trevena, Synact Pharma, Pluristem Therapeutics, UCB Pharma, Chiesi Farmaceutici, and others. Key Acute Respiratory Distress Syndrome Pipeline Therapies: Itolizumab, ZYESAMI, Lenzilumab, Remestemcel-L, Brexanolone, SFX-01, DMX-200, Tradipitant, Siltuximab, VERU 111, BIO 11006, FP025, Alteplase, Sarconeos Zavegepant, EB 05, USB 002, Sinapultide, Glenzocimab, DB 001, FX06, APN01, TRV 027, AP1189, PLX PAD, Zilucoplan, CHF5633, and others. Dive deep into rich insights for new drugs for ARDS treatment; visit @ Acute Respiratory Distress Syndrome Medications Table of Contents For further information on the acute respiratory distress syndrome pipeline therapeutics, reach out @ Acute Respiratory Distress Syndrome Drug Treatment Related Reports Acute Respiratory Distress Syndrome Market Acute Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key acute respiratory distress syndrome companies, including Cellular Biomedicine Group, Baylx, Histocell, Cartesian Therapeutics, Cynata Therapeutics, Immunovative Therapies, Orbsen Therapeutics, Celularity, Bonus BioGroup, Diffusion Pharmaceuticals, among others. Respiratory Distress Syndrome Market Respiratory Distress Syndrome Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key respiratory distress syndrome companies, including Dimerix Bioscience, Vanda Pharmaceuticals, EUSA Pharma, Veru Inc., BioMarck Pharmaceuticals, CTI BioPharma, Athersys, Foresee Pharmaceuticals, Boehringer Ingelheim, among others. Chronic Obstructive Pulmonary Disease Market Chronic Obstructive Pulmonary Disease Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key chronic obstructive pulmonary disease companies, including Sanofi, Chiesi Farmaceutici S.p.A., United Therapeutics Corporation, Verona Pharma, among others. Asthma Pipeline Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key asthma companies, including GSK, AstraZeneca, Teva Pharmaceuticals, among others. Severe Asthma Pipeline Severe Asthma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key severe asthma companies, including AstraZeneca, Novartis, Sanofi, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Additionally, get in touch with our business executive to explore @ Healthcare Due Diligence Services Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

09 Nov 2022

·www.globenewswire.com

Trevena Announces Completion of Phase 1 Study for TRV045, Novel S1P Receptor Modulator

TRV045 demonstrated a favorable tolerability profile with no reported SAEs and no lymphopenia Nonclinical study showed anti-inflammatory signaling, suggesting a potential disease-modifying effect of TRV045 in the treatment of epilepsy, based on astrocyte cell culture study PK profile supports anticipated once daily dosing CHESTERBROOK, Pa., Nov. 09, 2022 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced positive clinical data for TRV045, its selective sphingosine-1-phosphate subtype 1 (S1P1) receptor modulator. The 3-part randomized, double-blind, placebo-controlled Phase 1 study evaluated safety, tolerability and PK in healthy volunteers. TRV045 is being developed as a potential treatment for diabetic neuropathic pain (DNP). Through a collaboration with the National Institutes of Health, the Company is also exploring TRV045 as a potential treatment for epilepsy. “We’re pleased to report positive Phase 1 data on our novel S1P1 receptor modulator, TRV045, which are consistent with its distinct mechanism of action,” said Carrie Bourdow, President and CEO of Trevena. “Planning is underway to initiate a targeted proof-of-concept study early next year, which would provide near-term data to further validate TRV045’s potential in CNS areas of interest, including epilepsy and non-opioid chronic pain.” Overview of the TRV045 Phase 1 Clinical Program This study was a three-part study design, examining the PK profile, safety and tolerability of orally administered TRV045 in healthy volunteers. Part 1 – Single Ascending Dose: This study phase investigated the PK profile, safety and tolerability of single ascending doses of TRV045 or placebo. Doses were administered to 53 healthy subjects in 6 separate study cohorts, with TRV045 dosed at 5, 15, 30, 90, and 200mg. Part 2 – Food Effect: This study phase investigated the PK profile, safety and tolerability of TRV045 administered with a high-fat meal in 3 study cohorts. The effect of food on the absorption and exposure to TRV045 was studied in 27 subjects at doses of 30, 200 and 300mg. Part 3 – Multiple Dosing: This study phase investigated the PK profile, safety and tolerability among a single cohort of subjects receiving multiple doses of TRV045 or placebo. A single cohort of 9 subjects were given 250mg of TRV045 daily for seven days. Topline results from the Phase 1 study are summarized below: Well Tolerated. TRV045 was well tolerated, with no serious adverse events. Among non-serious spontaneous adverse events, the only adverse event assessed by study investigators as probably or definitely related to drug was headache in 4 subjects across all three parts of the study.Attractive PK. The PK profile of TRV045 showed a half-life consistent with anticipated once-daily dosing.Suitable Target Exposure. Based on the PK exposure, the calculated free plasma concentrations of TRV045 exceeded the targeted efficacy range based on nonclinical measures of in vitro and in vivo pharmacodynamics.Differentiated From Currently Marketed S1P Drugs. A targeted set of laboratory measures were studied to characterize the tolerability of TRV045, including total lymphocyte counts, ECGs, and ophthalmologic examinations, as these adverse events have been associated with existing S1P-targeted compounds. No lymphopenia, cardiac, pulmonary or ophthalmologic adverse events were reported in the Phase 1 study for TRV045. Astrocyte Cell Culture Study Trevena conducted an additional nonclinical study that showed TRV045 has a potential anti-inflammatory effect on astrocytes. This suggests TRV045 may play a role as a disease-modifying treatment in epilepsy. In this study, primary astrocytes derived from mouse brains were isolated and studied in cell culture. Astrocytes are highly prevalent glial cells that are well recognized mediators of inflammation in the CNS. Concentrations of seventeen different cytokines and chemokines produced by astrocytes were studied. The results demonstrated that TRV045 modulated these cytokines and chemokines, with a statistically significant dampening of the inflammatory response of these cells. We believe these data are potentially significant because inflammatory signals from astrocytes and other brain cells appear to play an important role in development of seizures and the emergence of epilepsy. As a result, we believe TRV045 may have the potential to exert disease-modifying effects in the treatment of epilepsy in humans. About Epilepsy Epilepsy, one of the most common neurological diseases in the world, is a chronic disorder characterized by recurrent seizures. Epilepsy is defined as having two or more unprovoked seizures separated by at least 24 hours or after one seizure with a high risk of more. A seizure is a sudden surge of electrical activity in the brain caused by complex chemical changes that occur in nerve cells. Usually, there is a balance of cells that either encourage or stop other brain cells from sending messages. A seizure occurs when there may be too much or too little electrical activity in the brain causing an imbalance. Seizures are a symptom of many different disorders that can affect the brain. Nearly 50 million people suffer from epilepsy worldwide, including 3 million adults and 470,000 children in the U.S. 150,000 new cases of epilepsy are reported in the United States each year. According to the CDC, 56% of adults living with diagnosed epilepsy continue to have seizures. About Diabetic Neuropathic Pain Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes, with pain in the extremities being one of the main symptoms. Other symptoms may include numbness, tingling, allodynia and hyperalgesia. Diabetic neuropathic pain is usually characterized as moderate to severe in nature and can substantially affect patients’ quality of life as well as their social and psychological well-being. Approximately 25% of people with diabetes are affected by DNP, equaling over 5 million people in the U.S. During their lifetime, approximately 50% to 70% of diabetic patients may experience symptoms of DNP. About TRV045 TRV045 is a novel, selective sphingosine-1-phosphate subtype 1 (S1P1) receptor modulator being developed as a potential treatment for acute and chronic neuropathic pain secondary to diabetic peripheral neuropathy. Through a collaboration with the National Institutes of Health, Trevena is also exploring TRV045 as a potential treatment for epilepsy. S1P receptors are located throughout the body, including the central nervous system, where they are believed to play a role in modulating neurotransmission and membrane excitability. Trevena's discovery efforts have identified a family of compounds that are highly selective for the S1P1 receptor. TRV045 reversed thermal hyperalgesia, a measure of neuropathic pain, in nonclinical models of diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy. TRV045 was not associated with lymphopenia and produced no changes in blood pressure, heart rate, or respiratory function at or above pharmacologically active doses in nonclinical studies. TRV045 is an investigational drug and has not been approved by the FDA. About Trevena Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes four differentiated investigational drug candidates: TRV250 for the acute treatment of migraine, TRV734 for maintenance treatment of opioid use disorder, TRV045 for diabetic neuropathic pain and epilepsy, and TRV027 for acute respiratory distress syndrome and abnormal blood clotting in COVID-19 patients. For more information, please visit www.Trevena.com Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candidates, commercialization of approved drug products and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “objective,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” “ongoing,” or the negative of these terms or similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the commercialization of any approved drug product, the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of the discussions with the FDA or other regulatory agencies about any and all of its programs; uncertainties related to the commercialization of OLINVYK; available funding; uncertainties related to the Company’s intellectual property; uncertainties related to the ongoing COVID-19 pandemic, other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates; and other factors discussed in the Risk Factors set forth in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date hereof. The Company anticipates that subsequent events and developments may cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, except as may be required by law. For more information, please contact: Investor Contact: Dan FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com(617) 430-7576 PR & Media Contact: Sasha BennettAssociate Vice PresidentClyde GroupSasha.Bennett@clydegroup.com(239) 248-3409

27 Jan 2022

·www.biospace.com

Trevena Announces Submission of New Drug Application in China for OLINVYK® by its Partner Jiangsu Nhwa Pharmaceutical

Trevena, Inc., (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced that China’s National Medical Products Administration (NMPA) has accepted submission of a New Drug Application (NDA) for oliceridine injection. The NDA was submitted by Trevena’s partner, Jiangsu Nhwa Pharmaceutical, and follows completion by Nhwa of a Phase 3 bridging trial for OLINVYK (oliceridine) injection, a novel IV analgesic that has been approved in the United States by the Food and Drug Administration (FDA) for use in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. "We are pleased to see the data presented in Nhwa’s NDA submission are consistent with data from our registration studies in the US,” said Carrie Bourdow, President and CEO of Trevena. “We are confident that Nhwa is the right strategic partner to advance OLINVYK in China and believe that this collaboration has the potential to create significant value for our stakeholders over the years ahead.” Trevena executed an exclusive License Agreement in 2018 with Nhwa to develop, manufacture, and commercialize OLINVYK in China and is eligible to receive regulatory and commercial milestone payments as well a 10% royalty on net sales in China. Nhwa’s submission to the NMPA included data from two clinical bridging studies in Chinese patients, based on feedback from China’s NMPA: a dose-escalation, open-label, single-dose study to evaluate the pharmacokinetics and safety profile; and a randomized, double-blind, positive-controlled Phase 3 bridging study in subjects with moderate to severe acute pain after abdominal surgery to evaluate the analgesic efficacy and safety of OLINVYK compared with IV morphine. The results of the Phase 3 bridging study show that the safety and pharmacokinetic pro oliceridine in Chinese patients is consistent with the data from global studies and demonstrates safety and tolerability in Chinese populations. The launch of OLINVYK in China, if approved by the NMPA, will help to address the significant unmet need in acute pain management. About Trevena Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes four differentiated investigational drug candidates: TRV250 for the acute treatment of migraine, TRV734 for maintenance treatment of opioid use disorder, TRV045 for diabetic neuropathic pain and epilepsy, and TRV027 for acute respiratory distress syndrome and abnormal blood clotting in COVID-19 patients. About Jiangsu Nhwa Pharmaceuticals Jiangsu Nhwa Pharmaceutical Co., Ltd., is a Chinese pharmaceutical company committed to setting new standards in CNS healthcare. Nhwa endeavors to provide innovative, high quality medicines to CNS patients with serious unmet medical needs. Nhwa offers a growing portfolio of more than 100 marketed products covering more than 6000 hospitals throughout China, including antipsychotics, anesthetics and analgesics, and neurological products. For more than 60 years, Nhwa has focused on CNS medicine, and every member of Nhwa's approximately 3,000-strong workforce is dedicated to improving patient health and outcomes. About OLINVYK® (oliceridine) injection OLINVYK is a new chemical entity approved by the FDA in August 2020. OLINVYK contains oliceridine, a Schedule II controlled substance with a high potential for abuse similar to other opioids. It is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK is available in 1 mg/1 mL and 2 mg/2 mL single-dose vials, and a 30 mg/30 mL single-patient-use vial for patient-controlled analgesia (PCA). Approved PCA doses are 0.35 mg and 0.5 mg and doses greater than 3 mg should not be administered. The cumulative daily dose should not exceed 27 mg. Important Safety Information WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS ADDICTION, ABUSE, AND MISUSE – OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing OLINVYK, and monitor all patients regularly for the development of behaviors or conditions. LIFE-THREATENING RESPIRATORY DEPRESSION – Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK. Monitor for respiratory depression, especially during initiation of OLINVYK or following a dose increase. NEONATAL OPIOID WITHDRAWAL SYNDROME – Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. RISK FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS – Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

100 Deals associated with TRV-120027

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12199

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute decompensated heart failure	Phase 2	Canada	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Israel	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Russia	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Hungary	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Czechia	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Poland	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Argentina	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Slovakia	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Romania	Trevena, Inc.	01 Dec 2013
Acute decompensated heart failure	Phase 2	Germany	Trevena, Inc.	01 Dec 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04924660 (NECTAR, CTgov)	Phase 2/3	Thrombosis \| COVID-19 \| Thrombophilia	1,060	TXA127 (TXA127 (4/20/2022 Arm Closed to Accrual))	hyowpbqlpb(ituhpovwiw) = jgyxkximwo zhnsooqleu (lpnlkawpus, yywljzwhyx - gajfrlgmfd) View more	-	22 Jan 2025
				TRV027 (TRV027 (4/20/2022 Arm Closed to Accrual))	hyowpbqlpb(ituhpovwiw) = qvuzsnniri zhnsooqleu (lpnlkawpus, rwetxpxawg - cbbjjfpstc) View more
NCT04419610 (CTgov)	Early Phase 1	COVID-19 \| Blood Coagulation Disorders	28	TRV027 (Patients With Confirmed/Suspected C19 Given Intervention)	fwsyxlbhqc(qjuutinhrp) = qivbijhmiu qntlbtgbkn (rrihevhxru, eyskcsnhvk - ykdaftijim) View more	-	01 May 2024
				sodium chloride 0.9% (Patients With Confirmed/Suspected C19 Given no Intervention)	fwsyxlbhqc(qjuutinhrp) = zfnzkrhzff qntlbtgbkn (rrihevhxru, csnukcpfls - wwoqotrgey) View more
NCT04924660 (Pubmed \| JAMA)	Phase 2/3	COVID-19	-	TXA-127	swkcltfhfn(unxjbmhmzt) = xzoerfmljd kejvcryxus (jdqqpdfbrd )	-	11 Apr 2023
				TRV-027	swkcltfhfn(unxjbmhmzt) = wjpunwahkw kejvcryxus (jdqqpdfbrd )
NCT04419610 (GlobeNewswire) Manual	Phase 1	COVID-19	21	TRV027	kefoqlnlpr(ttbqfxxiln) = aotcbnxxjw zzhmbyroxk (czjgrisusi ) View more	Positive	30 Sep 2021
				Placebo	kefoqlnlpr(ttbqfxxiln) = xchurlpgxa zzhmbyroxk (czjgrisusi ) View more

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