Real-world Effectiveness and Safety of Treatment With Direct Antiviral Agents (DAAs) in Patients With Chronic Hepatitis C and Cirrhosis in Southern Area of China

This is a multi-center, open-label clinical study. This study was aimed to assess the real-world effectiveness and safety of treatment with listed DAAs in patients with CHC and cirrhosis in Southern area of China.

Start Date30 Mar 2019

Sponsor / Collaborator

The Third Affiliated Hospital, Sun Yat-Sen University

EUCTR2018-002251-14-GB / Not yet recruitingPhase 4IIT

Localized on site testing and treatment of hepatitis C in homeless persons in London: a pilot non-randomised phase 4 interventional clinical trial of grazoprevir and elbasvir ± ribavirin in participants with genotype 1a, 1b or 4 to measure efficacy and adherence to treatment in a homeless population - ATTIC - Access To Treat in the Community

Start Date02 Jan 2019

Sponsor / Collaborator

King's College Hospital NHS Foundation Trust

NCT03706222 / CompletedNot ApplicableIIT

The Real World Analysis of Drug-Drug Interactions of Grazoprevir/Elbasvir in Treatment of Chronic Hepatitis C Patients in Taiwan

Co-morbid diseases often present in a substantial proportion of patients with chronic hepatitis C (CHC) and require drugs to treat and control. Grazoprevir/elbavir is metabolized by cytochrome P-450 enzyme of liver. Drug-drug interactions (DDIs) are important issue before commencing direct acting antiviral agents (DAA) treatment for CHC patients. Few studies from Western countries reported that the percentages of DDIs of grazoprevir/elbasvir are limited.In Asia, real-world analysis of DDIs of grazoprevir/elbasvir is lacking and needs to be clarified.

Start Date22 Oct 2018

Sponsor / Collaborator

National Cheng Kung University Hospital

[+1]

100 Clinical Results associated with Grazoprevir Hydrate

100 Translational Medicine associated with Grazoprevir Hydrate

100 Patents (Medical) associated with Grazoprevir Hydrate

366

Literatures (Medical) associated with Grazoprevir Hydrate

21 Dec 2023·Journal of biomolecular structure & dynamics

Molecular insights into the in silico discovery of corilagin from Terminalia chebula as a potential dual inhibitor of SARS-CoV-2 structural proteins

Article

Author: Kollur, Shiva Prasad ; Shirahatti, Prithvi S ; Frau, Juan ; Pradeep, Sushma ; Dharmashekara, Chandan ; Mandal, Subhankar P ; Reddy, Pruthvish ; Jain, Anisha ; Srinivasa, Chandrashekar ; Glossman-Mitnik, Daniel ; Ortega-Castro, Joaqúın ; Shivamallu, Chandan ; Flores-Holgúın, Norma ; Patil, Shashank M ; Patil, Sharanagouda S ; Ramu, Ramith

The spike (S) glycoprotein and nucleocapsid (N) proteins are the crucial pathogenic proteins of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus during its interaction with the host. Even FDA-approved drugs like dexamethasone and grazoprevir are not able to curb the viral progression inside the host and are reported with adverse effects on body metabolism. In this context, we aim to report corilagin a novel, potential dual inhibitor of S and N proteins from Terminalia chebula. The bioactive compounds of T. chebula were subjected to a series of computational investigations including molecular docking simulations, molecular dynamics (MD) simulations, binding free energy calculations, and PASS pharmacological analysis. The results obtained from these studies revealed that corilagin was highly interactive with the S (-8.9 kcal/mol) and N (-9.2 kcal/mol) proteins, thereby showing dual inhibition activity. It was also found to be stable enough to induce biological activity inside the inhibitor binding pocket of the target enzymes throughout the dynamics simulation run for 100 ns. This is also confirmed by the changes in the protein conformations, evaluated using free energy landscapes. Outcomes from this investigation identify corilagin as the lead potential dual inhibitor of S and N proteins of SARS-CoV-2, which could be taken for biological studies in near future.Communicated by Ramaswamy H. Sarma.

01 Oct 2023·Clinical pharmacokinetics

Mechanisms and Clinical Significance of Pharmacokinetic Drug Interactions Mediated by FDA and EMA-approved Hepatitis C Direct-Acting Antiviral Agents.

Review

Author: Murray, Michael

The treatment of patients infected with the hepatitis C virus (HCV) has been revolutionised by the development of direct-acting antiviral agents (DAAs) that target specific HCV proteins involved in viral replication. The first DAAs were associated with clinical problems such as adverse drug reactions and pharmacokinetic drug-drug interactions (DDIs). Current FDA/EMA-approved treatments are combinations of DAAs that simultaneously target the HCV N5A-protein, the HCV N5B-polymerase and the HCV NS3/4A-protease. Adverse events and DDIs are less likely with these DAA combinations but several DDIs of potential clinical significance remain. Much of the available information on the interaction of DAAs with CYP drug-metabolising enzymes and influx and efflux transporters is contained in regulatory summaries and is focused on DDIs of likely clinical importance. Important DDIs perpetrated by current DAAs include increases in the pharmacokinetic exposure to statins and dabigatran. Some mechanistic information can be deduced. Although the free concentrations of DAAs in serum are very low, a number of these DDIs are likely mediated by the inhibition of systemic influx transporters, especially OATP1B1/1B3. Other DDIs may arise by DAA-mediated inhibition of intestinal efflux transporters, which increases the systemic concentrations of some coadministered drugs. Conversely, DAAs are victims of DDIs mediated by cyclosporin, ketoconazole, omeprazole and HIV antiretroviral drug combinations, especially when boosted by ritonavir and, to a lesser extent, cobicistat. In addition, concurrent administration of inducers, such as rifampicin, carbamazepine and efavirenz, decreases exposure to some DAAs. Drug-drug interactions that increase the accumulation of HCV N3/4A-protease inhibitors like grazoprevir may exacerbate hepatic injury in HCV patients.

01 Oct 2023·JHEP reports : innovation in hepatology

Glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection: The TARGET3D study.

Article

Author: Grebely, Jason ; Cooke, Graham ; Iser, David ; Tu, Elise ; Kulasegaram, Ranjababu ; Shaw, David ; Bhagani, Sanjay ; Gane, Edward ; Stedman, Catherine ; Martinello, Marianne ; Matthews, Gail V ; Ustianowski, Andrew ; Orkin, Chloe ; Nelson, Mark ; Dore, Gregory J

Background & Aims:

Short duration treatment may aid HCV elimination among key populations. This study evaluated the efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection.

Methods:

In this single-arm multicentre international trial, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300 mg-120 mg daily for 4 weeks. Primary infection was defined as a first positive anti-HCV antibody and/or HCV RNA measurement within 6 months of enrolment and either acute clinical hepatitis within 12 months (symptomatic illness or alanine aminotransferase >10x the upper limit of normal) or antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months and prior clearance (spontaneous or treatment). The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) and per-protocol (PP) populations.

Results:

Twenty-three participants (96% men, 70% HIV, 57% ever injected drugs) received treatment, of whom 74% had genotype 1a infection and 35% recent reinfection. At baseline, median duration of infection was 17 weeks (IQR 11-29) and HCV RNA was 5.8 log₁₀IU/ml (IQR 5.2-6.9). SVR12 was achieved by 78% (18/23; 95% CI 56-93%) and 82% (18/22; 95% CI 60-95%) of the ITT and PP populations, respectively, and in 100% (12/12; 95% CI 74-100%) of participants with baseline HCV RNA ≤6 log₁₀. There were four cases of virological failure (relapse); three received retreatment with 12 weeks sofosbuvir-velpatasvir or grazoprevir-elbasvir (SVR, n = 2; loss to follow-up, n = 1). No serious adverse events were reported.

Conclusion:

While most achieved SVR, the efficacy of a 4-week regimen of glecaprevir-pibrentasvir was lower than observed with longer treatment durations (≥6 weeks) among people with recent HCV.

Trial Registration:

Clinicaltrials.gov Identifier: NCT02634008.

Impact and implications:

Short duration treatment may aid HCV elimination among key populations. This investigator-initiated single-arm multicentre international pilot trial demonstrated that efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection was sub-optimal (SVR12 78% ITT, 82% PP). Baseline HCV RNA appeared to impact response, with higher efficacy among participants with lower baseline HCV RNA (≤6 log₁₀; SVR12 100% ITT, 12/12). While most achieved SVR, the efficacy of 4 weeks of glecaprevir-pibrentasvir was below that seen with longer treatment durations (≥6 weeks).

News (Medical) associated with Grazoprevir Hydrate

10 Nov 2022

·www.biospace.com

Senti Bio Reports Third Quarter Financial Results and Pipeline Updates

- SENTI-202 on track for IND filing in 2023; clinical plans for SENTI-202 expand beyond AML to CD33 and/or FLT3 expressing hematologic malignancies including MDS - - Selected development candidate for program to treat GPC3-expressing solid tumors including HCC, SENTI-301A; expected IND filing in 2023 - - Preclinical data from two solid tumor CAR-NK programs highlighted at SITC - - Cash position of $114.9 million as of September 30, 2022; maintain expectation of cash runway into 2024 - SOUTH SAN FRANCISCO, Calif., Nov. 10, 2022 (GLOBE NEWSWIRE) -- Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio”), a biotechnology company innovating next-generation cell and gene therapies using its proprietary gene circuit platform, today reported financial results for the third quarter ended September 30, 2022, and highlighted recent pipeline advances, including an outline for its proposed Phase 1 clinical trial plans for SENTI-202, to include patients with CD33 and/or FLT3 expressing hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Senti Bio also selected SENTI-301A as the development candidate from its GPC3 targeting solid tumor program. SENTI-301A is a Multi-Armed off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy candidate designed for the treatment of GPC3 expressing tumors including hepatocellular carcinoma (HCC), the most common form of liver cancer in adults. In addition, Senti Bio’s data presentation at the Society for Immunotherapy of Cancer (SITC) Annual Meeting outlined continued progress with the solid tumor CAR-NK product candidate SENTI-301A and the SENTI-401 program. Both programs use Senti Bio’s proprietary gene circuit technology to potentially enhance activity against solid tumors by incorporating potent activating CARs and multifunctional cytokines to influence the tumor milieu as well as support enhanced CAR-NK activity. Specifically, SENTI-401 targets carcinoembryonic antigen (CEA) cell adhesion molecule 5 expressing solid tumors, including colorectal cancer (CRC), and also includes a NOT Logic Gate gene circuit to protect CEA expressing healthy cells from potential “on target, off tumor” killing. This Logic Gating strategy is designed to enable selective cytotoxicity of CAR-NK cells against tumor cells while protecting healthy cells. “I am proud of our continued progress toward the clinic with our CAR-NK cell therapy oncology programs for both hematologic malignancies and solid tumors. With SENTI-202, we believe that we have generated compelling preclinical data demonstrating the killing of primary AML and MDS tumor cells, while maintaining protection of healthy hematopoietic stem cells, to support a clinical trial aimed at both cancer types, and we remain on track to IND in 2023,” said Timothy Lu, MD, PhD, Chief Executive Officer and Co-Founder of Senti Bio. “In addition, we recently selected our development candidate, SENTI-301A, which is designed to treat GPC3 positive tumors including HCC, and are on track to IND in 2023.” Lu added, “Our scientists continue to generate exciting data across our pipeline; data from SENTI-301A and SENTI-401 are being highlighted today at the SITC Annual Meeting, and we are extremely excited to preview new data on SENTI-202 at the American Society of Hematology meeting next month. We remain steadfast in our vision of developing smarter medicines based on truly innovative advancements with our gene circuit technology platform.” RECENT PIPELINE HIGHLIGHTS CAR-NK Cell Oncology Pipeline and Gene Circuit Platform Highlights: SENTI-202: A Logic Gated off-the-shelf CAR-NK cell therapy development candidate designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies, such as AML and MDS, while sparing the healthy bone marrow. Announced the acceptance of an abstract for presentation at the American Society of Hematology (ASH) meeting in December 2022; preclinical data to highlight the use of Logic Gating gene circuits to target and eliminate AML cells while sparing healthy hematopoietic stem cells. Outlined plans for a proposed Phase 1 clinical trial, including a dose-finding phase in patients with relapsed and/or refractory CD33 and/or FLT3 expressing hematologic malignancies. Disease-specific expansion cohorts would include relapsed and/or refractory AML. Multiple doses of SENTI-202 administration following standard fludarabine/cyclophosphamide (Flu/Cy) lymphodepleting chemotherapy is planned along with a potential to receive multiple cycles. Clinical trial endpoints would evaluate safety and identification of a recommended Phase 2 dose of SENTI-202, as well as efficacy using standard disease-specific response criteria. Manufacturing efforts and GMP facility buildout remain on track towards enabling flexible clinical manufacturing of CAR-NK cells in 2023. An IND application for SENTI-202 is expected to be submitted to the U.S. Food and Drug Administration (FDA) in 2023. SENTI-301A: A Multi-Armed off-the-shelf CAR-NK cell therapy development candidate designed for the treatment of GPC3 expressing tumors, including HCC. Selected a development candidate, SENTI-301A, based on extensive optimization using Senti Bio’s proprietary screening platform for off-the-shelf CAR-NK cells with potent anti-tumor activity. SENTI-301A uses the following components: Engineered NK cells that target glypican 3 (GPC3), which is highly expressed in 70% to 90% of HCCs and has low or no expression on normal adult tissues. Calibrated release interleukin-15 (crIL-15), a multi-functional immuno-stimulatory payload designed to simultaneously stimulate surrounding immune cells and promote CAR-NK cell expansion, persistence and tumor killing. Preclinical data presented today at the SITC Annual Meeting demonstrates the use of gene circuits to improve the cytotoxicity and persistence of GPC3 targeting CAR-NK cells in treating HCC. Senti Bio’s novel GPC3 targeting activating CAR combined with crIL-15 technology provide the CAR-NK cells multi-arming to enhance persistence and killing activity of the NK cells, and to leverage the endogenous immune system for increased anti-tumor activity. The data presents evidence of robust in vitro and in vivo killing of relevant tumor cells with SENTI-301A. An IND application for SENTI-301A is expected to be submitted to the FDA in 2023 The presentation at the SITC Annual Meeting also includes data from ongoing development of Regulator Dial gene circuits that control expression of crIL-12 in response to FDA-approved small molecules. These data indicate that the Company’s Regulatory Dial gene circuits may be used with an expanded number of FDA-approved drugs to modulate crIL-12 expression, including tamoxifen and grazoprevir, among others. These data give the Regulator Dial the potential for broader applicability beyond GPC3 expressing cancers and thus, the Company is actively exploring the continued development of this gene circuit for product opportunities across a wide range of additional solid tumors. SENTI-401: A Logic Gated, Multi-Armed off-the-shelf selective CAR-NK cell therapy development program designed to precisely target CEA positive solid tumors (e.g., colorectal, pancreatic and lung cancers) while sparing healthy cells using the NOT Logic Gate. Presented preclinical proof-of-concept data at the SITC Annual Meeting that demonstrates the robust anti-cancer functionality of Logic Gated, Multi-Armed CAR-NK cells against a variety of colorectal cancer models: Evaluated ways to enhance NK cell persistence and function using a combination of crIL-15 and IL-21, a previously undisclosed Multi-Arming combination, resulting in significantly enhanced and durable killing of CEA positive target cells in vitro and in vivo. Long-term anti-tumor responses: a single dose of CEA targeting CAR-NK cells armed with crIL-15+IL-21 resulted in durable anti-tumor activity in human CRC xenograft models that express CEA, including complete tumor regressions. CAR-NK cells equipped with an optimized inhibitory CAR (iCAR) suppressed activating CAR (aCAR)-mediated killing of healthy cells that co-expressed VSIG2-and CEA without diminishing aCAR-mediated anti-tumor activity of CEA expressing tumor cells. THIRD QUARTER 2022 FINANCIAL RESULTS Cash and Cash Equivalents: As of September 30, 2022, Senti Bio held cash and cash equivalents of $114.9 million, which the Company believes is sufficient to fund operations into 2024. R&D Expenses: Research & development expenses were $8.1 million for the quarter ended September 30, 2022, compared to $5.4 million for the same period in 2021. The increase includes an additional $0.5 million in non-cash stock-based compensation expense. G&A Expenses: General and administrative expenses were $10.8 million for the quarter ended September 30, 2022, compared to $7.1 million for the same period in 2021. The increase includes an additional $1.2 million in non-cash stock-based compensation expense. Net Loss: Net loss was $16.6 million, or $0.38 per basic and diluted share, for the quarter ended September 30, 2022. CapEx: Capital expenditures were $14.2 million for the quarter ended September 30, 2022, primarily driven by the GMP manufacturing facility buildout and related equipment purchases. About Senti Bio Our mission is to create a new generation of smarter medicines that outmaneuver complex diseases using novel and unprecedented approaches. To accomplish this, we are building a synthetic biology platform that may enable us to program next-generation cell and gene therapies with what we refer to as Gene Circuits. These novel and proprietary Gene Circuits are designed to reprogram cells with biological logic to sense inputs, compute decisions and respond to their cellular environments. We aim to design Gene Circuits to improve the intelligence of cell and gene therapies in order to enhance their therapeutic effectiveness, precision, and durability against a broad range of diseases that conventional medicines do not readily address. Our synthetic biology platform utilizes off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cells, outfitted with Gene Circuit technologies, to target particularly challenging liquid and solid tumor oncology indications. Our lead product candidate is SENTI-202 for the treatment of CD33 and/or FLT3 expressing hematologic malignancies, such as AML and MDS. We are developing an additional CAR-NK product candidate, SENTI-301A, for the treatment of hepatocellular carcinoma (HCC) and other GPC3 positive cancers. We also have a CAR-NK program for the treatment of colorectal cancer (CRC) and other CEA positive cancers, SENTI-401. We have also demonstrated the breadth of our Gene Circuits in other modalities and diseases outside of oncology and have executed partnerships with Spark Therapeutics and BlueRock Therapeutics to advance these capabilities. Forward-Looking Statements This document contains certain statements that are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally are identified by the words “believe,” “could,” “predict,” “continue,” “ongoing,” “project,” “expect,” “anticipate,” “explore,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” “will be,” “will continue,” “will likely result,” “forecast,” “seek,” “target” and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations of Senti Bio’s management and assumptions, whether or not identified in this document, and, as a result, are subject to risks and uncertainties. Forward-looking statements include, but are not limited to, statements regarding estimates and forecasts of financial and cash runway and the sufficiency of such cash runway, Senti Bio’s ability to continue to advance its pipeline of preclinical programs and product candidates, Senti Bio’s research and development activities, the generation and release of additional preclinical data, commencement of IND-enabling studies and the timing of submission of IND filings, plans for a Phase 1 clinical trial, and GMP manufacturing start up activities, as well as statements about the potential attributes and benefits of Senti Bio’s product candidates and platform technology. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by any investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Senti Bio. Many factors could cause actual future events to differ materially from the forward-looking statements in this document, including but not limited to: (i) changes in domestic and foreign business, market, financial, political and legal conditions, (ii) changes in the competitive and highly regulated industries in which Senti Bio operates, variations in operating performance across competitors, changes in laws and regulations affecting Senti Bio’s business, (iii) the ability to implement business plans, forecasts and other expectations, (iv) the risk of downturns and a changing regulatory landscape in Senti Bio’s highly competitive industry, (v) risks relating to the uncertainty of any projected financial information with respect to Senti Bio, (vi) risks related to uncertainty in the timing or results of Senti Bio’s preclinical studies, IND filings, and GMP manufacturing startup activities, (vii) Senti Bio’s dependence on third parties in connection with preclinical and IND-enabling studies, IND filings, and GMP manufacturing buildout and startup activities, (viii) risks related to delays and other impacts from the COVID-19 pandemic, and (ix) the success of any future research and development efforts by Senti Bio. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of Senti Bio’s registration statement on Form S-1 (File No. 333-267390), and other documents filed by Senti Bio from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements in this document. There may be additional risks that Senti Bio does not presently know, or that Senti Bio currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements in this document. Forward-looking statements speak only as of the date they are made. Senti Bio anticipates that subsequent events and developments may cause Senti Bio’s assessments to change. Except as required by law, Senti Bio assumes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. Availability of Other Information About Senti Bio For more information, please visit the Senti Bio website at or follow Senti Bio on Twitter (@SentiBio) and LinkedIn (Senti Biosciences). Investors and others should note that we communicate with our investors and the public using our company website ( ), including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on Twitter and LinkedIn. The information that we post on our website or on Twitter or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Find more information at sentibio.com Follow us on Linkedin: Senti Biosciences Follow us on Twitter: @SentiBio Senti Biosciences, Inc. Unaudited Selected Consolidated Balance Sheet Data (in thousands) September 30, December 31, 2022 2021 Cash and cash equivalents $ 114,940 $ 56,034 Restricted cash 3,295 3,257 Property and equipment, net 47,259 12,368 Operating lease right-of-use assets 18,883 20,708 Total assets 189,441 96,702 Total liabilities 49,098 36,326 Redeemable convertible preferred stock — 171,833 Total stockholders’ equity (deficit) 140,343 (111,457 ) Senti Biosciences, Inc. Unaudited Consolidated Statements of Operations (in thousands, except share and per share data) Three Months Ended Nine Months Ended September 30, September 30, 2022 2021 2022 2021 Total revenue $ 1,766 $ 1,103 $ 4,227 $ 1,968 Operating expenses: Research and development 8,056 5,410 24,904 15,548 General and administrative 10,795 7,116 29,936 15,981 Total operating expenses 18,851 12,526 54,840 31,529 Loss from operations (17,085 ) (11,423 ) (50,613 ) (29,561 ) Total other income (expense), net 445 17 10,613 (14,854 ) Net loss $ (16,640 ) $ (11,406 ) $ (40,000 ) $ (44,415 ) Net loss per share, basic and diluted $ (0.38 ) $ (3.90 ) $ (1.99 ) $ (15.33 ) Weighted-average shares outstanding, basic and diluted 43,424,172 2,925,957 20,150,459 2,897,850 Senti Bio Contacts: Investors: investors@sentibio.com Media: Kelli Perkins kelli@redhousecomms.com

Financial StatementCell TherapyImmunotherapySmall molecular drug

30 Apr 2021

·www.biospace.com

Research Roundup: Underlying Conditions, COVID-19 Severity and More

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. More Data on Underlying Conditions and COVID-19 Severity A study out of RCSI University of Medicine and Health Sciences and the HSE Health Protection Surveillance Centre (HPSC) in Ireland has further defined the association between comorbidities and poor outcomes with COVID-19. The study took place between March and July 2020 and collected national data in Ireland from both hospital and community settings. It collected data for almost 20,000 confirmed cases of COVID-19. The results were published in The Lancet Regional Health – Europe. Of the patients studied, there were 1,476 deaths, 2,811 hospitalizations, and 438 ICU admissions. The conditions that carried the most risk were chronic heart disease, a chronic neurological condition, chronic kidney disease and cancer. Morbid obesity was also identified as being associated with severe outcomes. “Previous studies conducted have suggested that specific underlying conditions influence adverse health outcomes among those with a confirmed diagnosis of COVID-19,” said Kathleen Bennett, associate professor in Biostatistics, RCSI. “However, the majority of these studies have focused on hospital-based or local populations only. This study is the first population-based research to capture data across all settings in Ireland, including both community and hospital settings and so it gives us a better picture of the impact of the disease on patients at the population level.” Gilead’s Remdesivir Plus Hep C Drugs Effective Against COVID-19 Researchers with Mount Sinai Hospital and Mount Sinai School of Medicine tested a combination of Gilead’s remdesivir, an antiviral drug, with repurposed drugs for hepatitis C virus (HCV). The combinations, they found, were 10-times more effective at inhibiting SARS-CoV-2, the virus behind COVID-19. Four HCV drugs in combination with remdesivir improved the efficacy of remdesivir. They were simeprevir, vaniprevir, paritaprevir, and grazoprevir. The research group tested 10 HCV drugs, some already approved by the U.S. Food and Drug Administration (FDA). They utilized a supercomputer to model how drugs bind to viral proteins and predicted that those 10 would bind tightly to the SARS-CoV-2 Main protease (Mpro). They also found that seven of the drugs inhibited the SARS-CoV-2 protease. They then tested the seven drugs in monkey and human cells in culture. Four of the HCV drugs inhibited a different SARS-CoV-2 protease called PLpro. It was the four drugs that targeted PLpro that increased the efficacy of remdesivir by as much as 10-fold. While remdesivir must be dosed intravenously, the four HCV drugs are oral. Type 2 Diabetes Associated with Muscle Gene Researchers at Lund University found that in type 2 diabetes, a specific gene related to muscle cells is less active than it is in other people. The gene, VPS39, is important for when muscle cells absorb sugar from blood and build new muscle. In type 2 diabetes, the body’s ability to generate insulin is impaired, resulting in chronically increased blood sugar. The muscles are generally worse at absorbing sugar from food, and this muscle function and strength are typically impaired in type 2 diabetic patients. Their study, which was on muscle stem cells in type 2 diabetes patients compared to healthy controls, found that there were more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not appear to function in the same way in cells from people with type 2 diabetes did. How Brain Cells in Alzheimer’s Patients Lose Their Identity Investigators with the Salk Institute grew neurons that resemble better than ever before the brain cells in older patients. It appears to have given them insight into how the brain cells go off-track in Alzheimer’s patients, losing their cellular identity. The brain cells were characterized by markers of stress in addition to changes where the cells become less specialized. This is similar to what has been observed in cancer cells. The researchers collected skin cells from 13 sporadic, age-related Alzheimer’s patients, as well as cells from three people with the rarer, inherited form of Alzheimer’s. Their controls were skin cells from 19 people age-matched but without Alzheimer’s. Using fibroblasts, they induced neurons, then compared the molecular differences in the cells. They found that the cells from people with Alzheimer’s had specific characteristics different from the healthy control cells. The Alzheimer’s cells lacked synaptic structures, which are vital to sending signals to each other. There were also changes in signaling pathways, which control cell function, an indication the cells were under stress. They also found that the induced Alzheimer’s neurons had similar molecular signatures to immature nerve cells found in the developing brain. What this was interpreted to mean was the Alzheimer’s-based cells had lost their mature identity. A New Anti-Aging Compound Scientists at Washington University School of Medicine found a natural compound, nicotinamide mononucleotide (NMN), that in earlier studies seemed to counteract aging and improved metabolic health in mice, also had positive clinical effects in people. They conducted a clinical trial of postmenopausal women with prediabetes. They demonstrated that NMN improved the ability of insulin to increase glucose uptake in skeletal muscle. This ability is often abnormal in obese, prediabetic or type 2 diabetics. NMN improved expression of genes involved in muscle structure are remodeling. However, it did not lower blood sugar levels, blood pressure, improve blood lipids, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as was observed in mice. “Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said Samuel Klein, senior investigator and the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvement in other markers of metabolic health, which we did not detect in our study participants.”

100 Deals associated with Grazoprevir Hydrate

External Link

KEGG	Wiki	ATC	Drug Bank
-	Grazoprevir Hydrate	J05AP11	DB11575

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis C	JP	Merck Sharp & Dohme Corp.	28 Sep 2016

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C, Chronic	Phase 2	-	Merck Sharp & Dohme Corp.	23 May 2014

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03379506 (5172-079 \| MK-5172-079, CTgov)	Phase 2	Hepatitis C	57	GZR (Age Cohort 1: 12 to <18 Years: Mini and Expanded)	xtvlbgfszr(vbvagqcimc) = fslxtoxgwl ebxlfpjlny (qfmlegvvut, rsfdfestgw - vebyrnieaf) View more	-	17 Aug 2020
NCT03379506 (5172-079 \| MK-5172-079, CTgov)	Phase 2	Hepatitis C	57	GZR (Age Cohort 2: 7 to <12 Years: Mini and Expanded)	xtvlbgfszr(vbvagqcimc) = qfjhmgpxom ebxlfpjlny (qfmlegvvut, clplhazite - mbpzneirwb) View more	-	17 Aug 2020
NCT01716156 (P039 \| 5172-039, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	26	Grazoprevir 100 mg + Ribavirin 12 weeks	nsfswcpxtx(slfrrxxecy) = zhcgownsdq oiwqiszcpg (bndvnnzlpj )	-	01 Oct 2016
NCT01716156 (P039 \| 5172-039, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	26	Grazoprevir 100 mg + Ribavirin 24 weeks	nsfswcpxtx(slfrrxxecy) = gzarppfqhu oiwqiszcpg (bndvnnzlpj )	-	01 Oct 2016
NCT02092350 (C-SURFER \| 5172-052, CTgov)	Phase 2/3	Hepatitis C, Chronic \| Chronic Kidney Diseases	237	Placebo to Grazoprevir+Grazoprevir	aqbaywnkac(pbjumdkosh) = uhpoflejst sakyplzdrc (comoxjdbeb, wtjumitnhj - qnzbjlwlap) View more	-	12 Apr 2016
NCT01537900 (5172-010, CTgov)	Phase 1	Hepatitis C	4	Grazoprevir	uobtcrkywa(cincfdwpxo) = lyvioimcdf niwdusifjz (kmusyocmuh, xlrvxpngmt - hknagmujsm) View more	-	04 Mar 2016
NCT01390428 (5172-013, CTgov)	Phase 1	Hepatitis C	50	Grazoprevir (Part 1-Healthy Matched to Mild HI)	jhyubpqifx(xhhuichqpk) = lbglcdrbzn nlbsojbtez (bktrwqnaum, pbaghrgszq - fvwroilbqk) View more	-	04 Mar 2016
NCT01390428 (5172-013, CTgov)	Phase 1	Hepatitis C	50	Grazoprevir (Part 2-Moderate HI)	jhyubpqifx(xhhuichqpk) = ggholvnanf nlbsojbtez (bktrwqnaum, txvtagwvim - sowiajqeuq) View more	-	04 Mar 2016
NCT01440595 (5172-012, CTgov)	Phase 2	Chronic hepatitis C genotype 2 \| Chronic hepatitis C genotype 3	5	Grazoprevir+Peginterferon alfa-2b (Peg-IFN)+ribavirin (RBV) (Grazoprevir 400 mg + Peg-IFN + RBV)	xozgedwchs(fopigavpga) = aippuomtlg lzfmfqwmgn (adghhcwzid, esianpyrhp - blebnpeops) View more	-	04 Mar 2016
NCT01440595 (5172-012, CTgov)	Phase 2		5	Placebo to Grazoprevir+Peginterferon alfa-2b (Peg-IFN)+ribavirin (RBV) (Placebo + Peg-IFN + RBV)	xozgedwchs(fopigavpga) = dzblkrxjyc lzfmfqwmgn (adghhcwzid, enarnrafha - bibvncdfpv) View more	-	04 Mar 2016
NCT02105454 (5172-048, CTgov)	Phase 2	Hepatitis C, Chronic	79	Grazoprevir (GZR)+Elbasvir (EBR)+ribavirin (RBV)	gsougquild(hxcvvggvze) = mwjuoltuzl sdlldcqiiu (vfycymahtn, yweosvuqqm - mfqwsctzuq) View more	-	04 Mar 2016
NCT02105454 (5172-048 \| C-SALVAGE, Pubmed \| J Hepatol) Manual	Phase 2	Hepatitis C, Chronic	79	Grazoprevir and elbasvir+ribavirin	nhllpgtyay(bchzrbwcio) = kdobksozzh weopqzqpux (elfugelsdn )	Positive	01 Sep 2015
NCT02105662 (C-EDGE CO-INFECTION, Pubmed \| Lancet HIV) Manual	Phase 3	HIV Infections \| Hepatitis C	218	grazoprevir and elbasvir	omipyoyzmo(cnbenjmnot) = fatigue (29; 13%), headache (27; 12%), and nausea (20; 9%) lhxxhyembb (waaqyaghxl )	Positive	01 Aug 2015

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