IMPDH inhibitors(Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors), RNAP inhibitors(Bacterial DNA-directed RNA polymerase inhibitors), mRNA guanylyltransferase inhibitors

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Compensated cirrhosisHepatitis CHepatitis C, Chronic+ [1]

Inactive Indication

Acute hepatitisAnemiaChronic hepatitis C genotype 1+ [16]

Originator Organization

Bausch Health Cos., Inc.

Active Organization

Chengdu First Pharmaceutical Co. Ltd.

Merck Sharp & Dohme Corp.

Chugai Pharmaceutical Co., Ltd.

+ [1]

Inactive Organization

AbbVie, Inc.Hoffmann-La Roche, Inc.Biopartners GmbH

+ [8]

Drug Highest PhaseApproved

First Approval Date

US (31 Dec 1985),

Respiratory Syncytial Virus Infections

RegulationOrphan Drug (US)

Structure

Molecular FormulaC8H12N4O5

InChIKeyIWUCXVSUMQZMFG-AFCXAGJDSA-N

CAS Registry36791-04-5

917

Clinical Trials associated with Ribavirin

NCT06212336 / Not yet recruitingPhase 2/3IIT

Efficacy, Tolerability and Safety of New or Repurposed Drugs Against Lassa Fever in West African Countries

Lassa fever (LF) is a viral haemorrhagic fever responsible of 5000 deaths per year in West Africa, with in-hospital mortality at 12%. Transmission to humans occurs mainly via direct or indirect exposure to excreta from the rodent reservoir, mainly made up of Mastomys natalensis . Less frequently, LASV may also be transmitted from human to human and cause nosocomial outbreaks. Ribavirin is the only treatment available with worrying toxicity, questionable efficacy and low access because of its high cost. Consequently, there is an urgent need for new drugs to treat LF patients. The Research and Development (R&D) Blueprint of the World Health Organization (WHO) has included LF in the list of priority diseases for urgent research and development.
The INTEGRATE consortium is an unprecedented international collaboration on Lassa fever of 15 partners from 10 countries across West Africa, Europe and North America and across several disciplines (epidemiological researchers, social scientists, medical health facility professionals, humanitarian actors, etc.).

Start Date01 Jul 2024

Sponsor / Collaborator

Bernhard-Nocht-Institut für Tropenmedizin

[+6]

NCT06488300 / Not yet recruitingPhase 2IIT

Assessment of Respiratory SYNcytial Virus antivirALs: A Phase 2 Multi-centre Adaptive Randomised Platform Trial For the Assessment of Antiviral Pharmacodynamics in aCute Symptomatic RSV Infection (ARSYNAL-FC)

This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated Respiratory Syncytial Virus (RSV), to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential adaptive platform trial, we will assess and compare the performance of currently licensed interventions (including repurposed drugs) with activity against RSV, and those with potential activity demonstrated in pre-clinical and early clinical studies relative to each-other, and the control (no antiviral treatment).
ARSYNAL-FC study is funded by Wellcome Trust Grant ref: 226933/Z/23/Z through the COVID-19 Therapeutics Accelerator

Start Date01 Jul 2024

Sponsor / Collaborator

University of Oxford

ChiCTR2400082642 / RecruitingEarly Phase 1IIT

A randomized controlled study on the safety and efficacy of a ribavirin spray for the treatment of allergic rhinitis

Start Date02 Apr 2024

Sponsor / Collaborator-

100 Clinical Results associated with Ribavirin

100 Translational Medicine associated with Ribavirin

100 Patents (Medical) associated with Ribavirin

15,568

Literatures (Medical) associated with Ribavirin

01 Jan 2025·BRAIN BEHAVIOR AND IMMUNITY

Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study

Article

Author: Harrison, Neil A. ; Periche-Tomas, Eva ; Tibble, Jeremy ; Pariante, Carmine ; Cattaneo, Annamaria ; Bullmore, Edward T. ; Bone, Claudia ; Bullmore, Edward T ; Cattane, Nadia ; Harrison, Neil A

INTRODUCTION:

Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis-C virus (HCV) infection. Though clinically effective, IFN-α frequently induces functionally impairing mood and motivation symptoms, particularly fatigue. Unlike mood impairment, which typically emerges after weeks of treatment, fatigue tends to emerge and evolve rapidly, typically within hours of the first IFN-α injection. Despite being a major source of functional impairment during IFN-α and other immune-based therapies, the biological mechanisms underlying fatigue remain poorly understood. Here, we aimed to identify acute immune-response signatures to IFN-α that could predict the later development of fatigue.

METHODS:

In this exploratory study, we analyzed whole blood transcriptomics in a longitudinal sample of 27 HCV patients initiating IFN-α and Ribavirin therapy. Blood samples were obtained at baseline and 4½ hours after the first IFN-α dose and transcriptomic data was obtained using Affymetrix Human Gene 1.1 ST Array Strips. Gene expression data visualization and quality control were assessed using Partek Genomics Suite V6.6 and protein-protein interaction networks using STRING and Ingenuity Pathway Analysis (IPA). A Fatigue Visual Analogue Scale (fVAS) was utilized to record fatigue symptoms at baseline, 4½ hours and 4 weeks after initiation of treatment.

RESULTS:

IFN-α was associated with an upregulation of 526 transcripts and a downregulation of 228 genes, indicating a rapid transcriptomic response in whole blood within 4½ hours of injection. 93 genes were significantly positively correlated with changes in fatigue, with gene expression changes measured from baseline to 4.5 h and increases in fatigue assessed from baseline to week 4 on the fVAS. We identified a novel network of predominantly cytosolic ribosomal units and ubiquitin proteins implicated in modulating mTOR signaling that was associated with the development of fatigue 4 weeks after initiation of IFN-α treatment (p = 0.0078).

CONCLUSION:

Our findings suggest that acute activation of this anabolic/catabolic network by IFN-α may predispose to the experience of fatigue similar to evidence found in cancer-related fatigue. Further investigation is warranted to confirm the exploratory nature of these observations.

31 Dec 2024·Emerging Microbes & Infections

A novel BSL-2 Lassa virus reverse genetics system modelling the complete viral life cycle

Article

Author: Zhong, Jin ; Bai, Xu ; Xing, Yifan ; Hu, Xiaoyou ; Tian, Fangling ; Tong, Yimin ; Shi, Yi

Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.

01 Dec 2024·Biomedical Reports

Prolonged use of pentoxifylline increases the life expectancy of patients with compensated cirrhosis: A 20‑year retrospective study.

Article

Author: Villaseñor-García, Martha ; Jiménez-Luévano, Miguel Ángel ; Bravo-Hernández, Alejandro ; Gutiérrez-Ortíz, Jesús Alejandro ; Orozco-Alonso, Eduardo ; Bravo-Cuellar, Alejandro ; Jiménez-Partida, Ana Emilia ; Hernández-Flores, Georgina ; Sierra-Díaz, Erick

Liver cirrhosis is a pathology of varied etiology with a high prevalence and mortality, resulting in >1 million mortalities per year. Patients with liver cirrhosis typically have a survival time of 12 years following diagnosis. The treatment for this disease is directed at the complications of cirrhosis; however, to the best of our knowledge, the long-term management of patients with cirrhosis has been scarcely studied. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with rheological activity and antioxidant, anti-inflammatory and antifibrotic properties. PTX has been used in the treatment of peripheral arterial disease, inflammatory liver diseases and hepatocellular carcinoma with encouraging results. The aim of the present study was to evaluate the effect of PTX use on the survival of patients with compensated cirrhosis. For this purpose, a cross-sectional study was performed at the Gastroenterology and Hepatitis C Department of Dr. Valentín Gómez Farias Hospital (Institute for Security and Social Services for State Workers, Zapopan, Mexico) from June, 1996 to December, 2019. The follow-up time for these patients was 22.6 years (up to the end of the study period). In the present study, 326 patient files were analyzed and 118 patients with the disease were identified, 81 of whom (68.64%) died within 12 years after diagnosis. Of the included patients, 26 received PTX combined with PEG IFN-α-2a plus ribavirin, and 11 received PTX plus propranolol, with a median treatment duration of 20.6±0.8 years. Furthermore, 16 patients (43%) did not develop co-morbidities within this time, and the transition to decompensated cirrhosis was 16.6 years, with a survival time of 20 years. Therefore, the results of the present study suggest that PTX may improve the long-term survival of patients with compensated cirrhosis, rendering PTX a candidate for repurposing in the treatment of hepatic cirrhosis.

News (Medical) associated with Ribavirin

22 Oct 2024

·www.biospace.com

Gilead to Present Latest Research Across Key Liver Disease Indication at the American Association for the Study of Liver Disease (AASLD) Meeting 2024

- Key Insights from Viral Hepatitis, PBC, and MASH/Fibrosis Studies Highlight Gilead’s Ongoing Commitment to Advancing Life-Changing Liver Disease Research - FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced new research to be presented at The Liver Meeting ® 2024, hosted by the American Association for the Study of Liver Diseases (AASLD) from November 15-19 in San Diego, Calif. More than 40 abstracts will be presented with key data, including 11 abstracts reporting new data on primary biliary cholangitis (PBC). The data will include findings from the RESPONSE trial that demonstrate the efficacy and safety pro Livdelzi ® (seladelpar) in people living with PBC and compensated cirrhosis. Additionally, data will be presented on the effects of Livdelzi on pruritus (chronic itching), a symptom that has significant impact on the quality of life of people living with PBC, along with interim long-term efficacy and safety results from the ongoing ASSURE study. Beyond PBC, Gilead will be presenting an interim analysis of the Phase 3 MYR301 study, which is evaluating people living with hepatitis Delta virus (HDV) who received bulevirtide monotherapy (2 mg for 144 weeks; 10 mg for 144 weeks; or 10 mg for 96 weeks) for chronic HDV and have been off treatment for 48 weeks. The study is evaluating whether or not patients treated with bulevirtide monotherapy for 2-3 years maintained virological and biochemical responses one year after stopping treatment. An additional 144-week analysis of patient-reported outcomes for individuals treated with bulevirtide 2 mg will also be presented, adding to the wealth of long-term data for the treatment for chronic HDV. “We’re excited to share our latest research at The Liver Meeting, as we push the boundaries of what’s possible in liver disease treatment. The breadth of this research reflects Gilead’s unwavering dedication to advancing life-changing science and shaping healthier futures for people living with liver disease,” said Anu Osinusi, Vice President of Clinical Development for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “The depth and range of our data, spanning both viral and inflammatory liver diseases, underscores our commitment to making a meaningful impact at every stage of a person’s journey in liver disease. Our goals go far beyond treatment alone—our work spans awareness, education, screening, diagnosis, and long-term care, all intending to address unmet needs and enhance treatment outcomes.” Gilead will also present hepatitis C virus (HCV) data which will include safety and tolerability outcomes for Epclusa ® (velpatasvir/sofosbuvir) in pregnant individuals with chronic HCV (the STORC study). As a special population that is often excluded from clinical research, these results may help clinicians better support pregnant people living with HCV, which in turn may reduce the risk of transmission to infants. Furthermore, real-world findings from the SVR10K study on HCV will be showcased, demonstrating the effects of direct-acting antivirals against all HCV genotypes across diverse regions. Late-breaking data from a Phase 2a open-label study assessing the safety and efficacy of novel combination therapies for chronic hepatitis B virus (HBV) will also be presented by Gilead. Key Abstracts at AASLD 2024: ID Abstract Title PBC 164 Efficacy and Safety of Seladelpar in Patients with PBC and Compensated Cirrhosis in the Phase 3 Placebo-controlled RESPONSE Trial 167 Attenuation, Near Resolution, and Prevention of Pruritis in Patients with PBC Treated with Seladelpar: A Secondary Analysis of Patterns of Pruritis Change in the RESPONSE Trial 4339 Alkaline Phosphatase Changes with Seladelpar Across Subgroups of Primary Biliary Cholangitis Patients in the RESPONSE Trial 4342 Seladelpar and Reductions in Lipids in Patients with Primary Biliary Cholangitis with and without Statin use in the Phase 3 Placebo-controlled RESPONSE Study 4341 Long-term Safety of Seladelpar 10 mg with up to 5 Years of Treatment in Patients with Primary Biliary Cholangitis Primary sclerosing cholangitis (PSC) 151 Associations Between Biomarkers and Magnetic Resonance Imaging-derived ANALI Score in Patients with Primary Sclerosing Cholangitis: Analysis from the Phase 3 PRIMIS Study HDV 1147 Efficacy and Safety of BLV Monotherapy for Chronic Hepatitis Delta: Post Treatment Results through 48 Weeks after the End of Treatment from an Interim Analysis of a Randomized Phase 3 Study MYR301 1193 Patient-reported Outcomes among Patients with Chronic Hepatitis Delta Treated with Bulevirtide 2 mg: A Long-term Analysis of the Phase 3 MYR301 Trial at 144 Weeks 139 Long-term Bulevirtide Monotherapy in Patients with HDV-related Compensated Cirrhosis: Effectiveness, Safety and Clinical Outcomes from the Retrospective Multicenter European Study (SAVE-D) HCV 222 Safety, Tolerability, and Outcomes of Velpatasvir/Sofosbuvir in Treatment of Chronic Hepatitis C Virus during Pregnancy (STORC) 1455 The SVR10K Study: A Real-world Data with Pangenotypic Direct-acting Antivirals across Multiple Diverse Regions 1476 Hepatitis C Treatment Uptake Differs by Gender among a Commercially Insured Population in the United States HBV 1380 Results from a Phase 2a, Open-label Study to Evaluate the Safety and Efficacy of Novel Combination Therapies Containing VIR-2218, Selgantolimod, and Nivolumab for the Treatment of Chronic Hepatitis B 1252 Effectiveness and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients with Suboptimal Response to Antiviral Therapy 1337 Characterization of Changes in Noninvasive Fibrosis Markers over 8 Years of Tenofovir-based Treatment in Chronic Hepatitis B Patients Enrolled in Two Phase 3 Trials Nonalcoholic steatohepatitis (NASH)/Fibrosis 1520 Prospective Validation of the Mediterranean Diet Adherence Screener (MEDAS) for Point-of-care Assessment of Diet Quality in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease For more information, including a complete list of abstract titles being presented at the meeting, please visit the AASLD website . In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for bulevirtide 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023 and a full MA was granted in Switzerland and Australia in 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide. Bulevirtide 10 mg is an investigational product and has not been approved anywhere. Cilofexor and selgantolimod are investigational compounds and are not approved by the FDA or any other regulatory authority; their safety and efficacy have not been established. Please see below for the U.S. Indications and Important Safety Information, including BOXED WARNINGS, for Epclusa and Livdelzi. U.S. Important Safety Information And Indication for EPCLUSA BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4 : Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations. Adverse Reactions The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug. Drug Interactions Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan. Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir. Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments. Indication EPCLUSA is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis. U.S. Important Safety Information for LIVDELZI Warnings and Precautions Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Adverse Reactions The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Drug Interactions OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI. Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure. CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions. Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. Pregnancy and Lactation Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235. Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI. Indication LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). About HDV HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within 5 years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV-positive individuals for HDV. About PBC PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with PBC. But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Epclusa, Hepcludex (bulevirtide), Livdelzi (seladelpar), cilofexor and selgantolimod (such as the ASSURE, RESPONSE, MYR301, STORC and SVR10K studies); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve bulevirtide for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of investigational programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Epclusa, Hepcludex, Livdelzi, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com

Phase 2Clinical ResultDrug ApprovalPhase 3

10 Jun 2024

·www.sciencedaily.com

How human derived RNA fragments help the Hepatitis E virus

Why does Hepatitis E become chronic in some patients, and why do medications not work? To find out, an international research team led by scientists from Bochum observed a patient with chronic Hepatitis E infection over a year. Repeated sequencing of the virus RNA showed that the virus incorporated various parts of the host's messenger RNA into its genome. This resulted in a replication advantage, which may have contributed to the infection becoming chronic. Why does Hepatitis E become chronic in some patients, and why do medications not work? To find out, an international research team led by scientists from Bochum observed a patient with chronic Hepatitis E infection over a year. Repeated sequencing of the virus RNA showed that the virus incorporated various parts of the host's messenger RNA into its genome. This resulted in a replication advantage, which may have contributed to the infection becoming chronic. "The so-called insertion of host RNA can possibly predict the transition of an acute infection to a chronic condition," says Dr Daniel Todt, head of the Computational Virology research group in the Department of Medical and Molecular Virology at Ruhr University Bochum, Germany. The researchers report in the journal Nature Communications on June 6, 2024. Sequencing of the virus population Around 20 million people worldwide contract Hepatitis E every year. Normally, the infection heals without consequences, but it can be life-threatening for pregnant women or people with suppressed immune systems. In some cases, it becomes chronic. There are no specific effective medications. The broad-spectrum antiviral drug Ribavirin is also used against Hepatitis E, but it does not always work. How can the virus evade the immune system? Why does the infection become chronic and not heal? The researchers wanted to find out and analyzed for the first time all virus populations of a chronically infected patient over a period of more than a year. They examined more than 180 individual sequences from blood samples in detail. Replication in Cell Culture Benefits from Host RNA "The Hepatitis E virus has a so-called hypervariable region in its genetic information, into which it can incorporate various RNA sequences from host cells," describes Daniel Todt. His team was able to show that the composition of this region changed massively during the observation period. Additionally, many different compositions occurred simultaneously. In cell culture experiments, it was shown that incorporating host RNA provided a replication advantage: The altered viruses could replicate better than others. "We assume that this is partly responsible for the infection becoming chronic and the therapy failing," says Daniel Todt. The researchers examined the composition of the host RNA incorporated into the virus to determine if there were any common features characterizing the gene segments. "However, we could not detect any meaningful similarities," says Todt. The incorporated gene sequences are predominantly those that are very common in host cells, indicating a random selection. "Possibly, during Hepatitis E infection, a race between the virus and the immune system occurs in the body," speculates Daniel Todt. If the virus manages to incorporate host RNA before the immune system successfully combats the infection, it may lead to a chronic course. "Host RNA in the viral genome could, in any case, serve as a biomarker in the acute phase of an infection, indicating early on that it is likely to become chronic." The researchers plan to expand their studies to larger cohorts of patients.

siRNA

04 Jun 2024

·www.biospace.com

The Sustained, Slow Declining, Blood Concentration Profile of NV-387 Enables Infrequent Dosing for Strong Antiviral Effect

A First-In-Class, Broad-Spectrum Antiviral Agent Intending To Revolutionize Treatment of Viral Infections Including RSV, COVID, Influenzas and More SHELTON, CT / ACCESSWIRE / June 4, 2024 / NanoViricides, Inc. (NYSE Amer.:NNVC) (the "Company"), a clinical-stage global leader in broad-spectrum antiviral nanomedicines, reports on the highly desirable blood concentration pro its lead clinical stage broad-spectrum antiviral agent NV-387 upon intravenous (I.V.) administration in a non-human primate (NHP) animal model. The Company has found that its lead nanoviricide broad-spectrum antiviral drug candidate NV-387, when given as a slow bolus intravenous infusion, resulted in a relatively flat plateau of blood concentration of the drug with very slow decline over a 24 hour period in a cynomolgus monkey model. The maximum concentration as well as the plateau concentration increased in a dose-dependent manner, as expected. This sustained drug level in the blood stream for a relatively long period of time enables infrequent dosing. It is the result of the unique polymeric design of NV-387. NV-387 is a "chemical nanomachine". It is made up of polymer with its size chosen to minimize loss by renal filtration. The observed pharmacokinetic pro NV-387 supports a once-daily or less frequent dosing regimen. The Company has already developed an injectable formulation of NV-387, namely NV-387 Solution for Injection, Infusion, and Inhalation. An injection of NV-387 would be useful for moderate to severe illness, especially because of the sustained blood pro requires infrequent dosing. An infusion would be suitable for severely ill hospitalized patients. Importantly, this NV-387 Solution can be readily delivered directly into the lungs of a patient using a simple handheld nebulizer over a period of a few minutes. Such delivery can enable direct attack on the virus where such attack is most needed in the cases of severe lung infection. The utility of NV-387 is extremely broad, reminiscent of the utility of antibiotics. We have found that NV-387 could cure lethal lung infection in RSV infected animals even with an oral dose. There is no approved drug for RSV treatment other than the toxic, last resort drug ribavirin, which was not very effective in this lethal study compared to NV-387. We have also found that NV-387 IV administration as well as PO (Oral) administration was substantially superior to each of the approved drugs Tamiflu, Rapivab and Xofluza in an Influenza A/H3N2 lethal lung infection model. We believe that NV-387 is expected to possess similar strong antiviral activity against Influenza A/H5N1 "Bird Flu" viruses as well. Our belief is based on the putative mechanism of NV-387. NV-387 is a host-mimetic, direct acting antiviral designed as decoy, to look like a cell decorated with sulfated proteoglycans, to which over 90% of human pathogenic viruses including H5N1 are known to bind. We have found that NV-387 has strong antiviral activity against all tested coronaviruses, including SARS-CoV-2 pseudovirions. NV-387 was substantially more effective than remdesivir in a lethal coronavirus infection animal study. We believe that NV-387 has a strong potential for the treatment of COVID as well as "Long COVID". COVID continues to cause substantially more fatalities annually than Influenza viruses. Long COVID has substantial personal as well as societal costs. Available drug, Paxlovid (Pfizer) has significant limitations for patient suitability. Thus a new drug against COVID and Long COVID is sorely needed. About NanoViricides NanoViricides, Inc. (the "Company") ( ) is a development stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide® class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. Additionally, nanoviricides mimick the host-side features that the viruses continue to require in spite of mutations, and therefore the viruses would be highly unlikely to escape the nanvoricide drugs. Our lead drug candidate is NV-387 (drug product NV-CoV-2) for the treatment of RSV, COVID-19, Long COVID, Influenza, Bird Flu H5N1, and other respiratory viral infections. NV-387 has successfully completed a Phase 1a/1b human clinical trial in healthy subjects with no reported adverse events even at the highest and repeated dosages. This trial was conducted by the drug sponsor, Karveer Meditech Pvt. Ltd., our licensee and collaborator in India. The Company is currently focused on advancing NV-387 into Phase II human clinical trials for treatment of RSV infection. Our other advanced candidate is NV-HHV-1 for the treatment of Shingles rash, HSV-1 "cold sores" and HSV-2 "genital ulcers". The Company cannot project an exact date for filing an IND for any of its drugs because of dependence on a number of external collaborators and consultants. The Company is also developing drugs against a number of viral diseases including oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus, Ebola/Marburg viruses, and certain Coronaviruses. The Company intends to obtain a license for poxviruses and/or enteroviruses if the initial research is successful. The Company's technology is based on broad, exclusive, sub-licensable, field licenses to drugs developed in these areas from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005. As is customary, the Company must state the risk factor that the path to typical drug development of any pharmaceutical product is extremely lengthy and requires substantial capital. As with any drug development efforts by any company, there can be no assurance at this time that any of the Company's pharmaceutical candidates would show sufficient effectiveness and safety for human clinical development. Further, there can be no assurance at this time that successful results against coronavirus in our lab will lead to successful clinical trials or a successful pharmaceutical product. This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc. are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products. The phrases "safety", "effectiveness" and equivalent phrases as used in this press release refer to research findings including clinical trials as the customary research usage and do not indicate evaluation of safety or effectiveness by the US FDA. "NOAEL" means "No-Observed-Adevrese-Event-Level", which is the maximum dosage employed at which there were no adverse events found in animal studies. "MTD" means "Maximum Tolerated Dose", which is the maximum dosage employed that does not compromise survival of the animals. FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. cGMP refers to current Good Manufacturing Practices. CMC refers to "Chemistry, Manufacture, and Controls". CHMP refers to the Committee for Medicinal Products for Human Use, which is the European Medicines Agency's (EMA) committee responsible for human medicines. API stands for "Active Pharmaceutical Ingredient". API means active pharmaceutical ingredient. Contact: NanoViricides, Inc. info@nanoviricides.com Public Relations Contact: MJ Clyburn, TraDigital IR clyburn@tradigitalir.com SOURCE: NanoViricides, Inc. View the original press release on accesswire.com

License out/in

100 Deals associated with Ribavirin

External Link

KEGG	Wiki	ATC	Drug Bank
D00423	Ribavirin	J05AP01	DB00811

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Compensated cirrhosis	JP	Merck Sharp & Dohme Corp.	29 Jul 2015
Hepatitis C	JP	Chugai Pharmaceutical Co., Ltd.	26 Jan 2007
Hepatitis C, Chronic	US	Merck Sharp & Dohme Corp.	03 Jun 1998
Respiratory Syncytial Virus Infections	US	Bausch Health US LLC	31 Dec 1985

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatocellular Carcinoma	Phase 3	-	AbbVie, Inc.	01 Jul 2015
Decompensated cirrhosis of liver	Phase 3	-	AbbVie, Inc.	24 Nov 2014
Kidney Failure, Chronic	Phase 3	-	AbbVie, Inc.	23 Sep 2014
Chronic hepatitis C genotype 1b	Phase 3	-	AbbVie, Inc.	01 Aug 2012
Anemia	Phase 3	-	Merck Sharp & Dohme Corp.	07 Dec 2009
Fibrosis, Liver	Phase 3	BE	Merck Sharp & Dohme Corp.	01 May 2006
Fibrosis, Liver	Phase 3	FR	Merck Sharp & Dohme Corp.	01 May 2006
Chronic hepatitis C genotype 3	Phase 3	DE	Hoffmann-La Roche, Inc.	01 Nov 2005
Chronic hepatitis C genotype 1	Phase 3	-	Merck Sharp & Dohme Corp.	01 Jul 2005
HIV Infections	Phase 3	CA	Hoffmann-La Roche, Inc.	01 Jul 2005

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AASLD2023	Not Applicable	Hepatitis C	452	Sofosbuvir/Velpatasvir	sowvsldlru(yjwgkgamym) = showed a significant decrease from baseline to SVR12(-2.91 vs. -3.11 P < 0.001) ijldbacvkf (ruhmxkmfbv ) View more	-	10 Nov 2023
				Sofosbuvir/Velpatasvir with Ribavirin
AASLD2023	Not Applicable	-	-	Standard 12-week ribavirin regimen	jzznuvgukh(tpqbadyuoi) = ctpqzamaun bqdthbnscp (nfpwjoywpf )	-	10 Nov 2023
				Response-guided ribavirin regimen	jzznuvgukh(tpqbadyuoi) = gzcvlrsblu bqdthbnscp (nfpwjoywpf )
AASLD2023	Not Applicable	Hepatitis C, Chronic	65	Sofosbuvir/Velpatasvir with Ribavirin	ypgntgfqsi(wnlfvkchzv) = brldcfjhuj ejwrxzrxto (nshzokmouw ) View more	-	10 Nov 2023
				Sofosbuvir/Velpatasvir without Ribavirin	ypgntgfqsi(wnlfvkchzv) = tnswprhvzw ejwrxzrxto (nshzokmouw ) View more
NCT01268579 (CTgov)	Not Applicable	Head and Neck Neoplasms	9	ribavirin	ivicignqgk(xxmyozcggq) = zstvrqeqyb dnoqdecxpu (vkfalpbhqi, uiwbxdmrkp - lklutxkurd) View more	-	02 Oct 2023
NCT02308241 (CTgov)	Not Applicable	Human Papillomavirus-Related Oropharyngeal Neoplasms	12	Ribavirin	ofomvdeblx(axelkchlpn) = rajuqszsnp ibiooifhms (euzflrepgm, uahjyznwjv - wdbgjvfquk) View more	-	05 Jan 2023
NCT04551768 (Pubmed) Manual	Phase 1	COVID-19 \| Respiratory Distress Syndrome	51	Kanamycin Sulfate	yzuaafbbqf(yccwittvfy) = Improvement of ≥1 level in clinical status severity was observed in 31.4% (16/51) and 78.4% (40/51) of patients at end-of-treatment and day 30, respectively. ktrbkdazjd (tbpswshvkd )	Positive	03 Nov 2022
NCT04605588 (CTgov)	Phase 2	COVID-19	7	Hydroxychloroquine+Nitazoxanide+ribavirin (Active Study Drug)	kpwvnwznxo(qwapzvhooo) = cjhqdqqxaq itjjypbmpx (rqublapjoa, ybsqqzprct - jhvvxxfeek) View more	-	05 May 2022
				Placebo Hydroxychloroquine (Placebo)	kpwvnwznxo(qwapzvhooo) = upvojjgjgf itjjypbmpx (rqublapjoa, xygkxzvksl - gmanfvdmlr) View more
NCT02939989 (MAGELLAN-3, CTgov)	Phase 3	Hepatitis C, Chronic	33	Sofosbuvir+Glecaprevir/Pibrentasvir+Ribavirin (Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks)	hpbjurwtwo(rikukizhfp) = nzoeeumhvj zeylvkjecn (gsjahvqmcr, qjxmquusrr - qfovhspaoi) View more	-	04 May 2022
				Sofosbuvir+Glecaprevir/Pibrentasvir+Ribavirin (Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks)	hpbjurwtwo(rikukizhfp) = agxqskgqnt zeylvkjecn (gsjahvqmcr, avfnvivaoa - vvtivaqvcn) View more
Pubmed Manual	Not Applicable	Hepatitis C	299	Sofosbuvir+Velpatasvir+Kanamycin Sulfate	tjsyyyopqi(chwcuuumgx) = jfcqnmoiyw mqrbpnldfl (jgwcgwxsqx, 95.4 - 99.3) View more	Positive	20 Apr 2022
NCT02308241 \| NCT01268579 (Pubmed \| Oral Oncol)	Not Applicable	HPV-related carcinoma	12	Ribavirin	wtwhwwmwxt(ahnjhlhayv) = All patients had anemia (grades 1-3), with 33% having at least 1 dose reduction. obnllqokif (dvivcylvpq ) View more	Negative	22 Mar 2022

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis