Rosiglitazone Maleate

Researchers have discovered the biochemical workings of an old-fashioned diabetes drug, and it's helping them develop new, safer alternatives. Thiazolidinediones (TZDs) are a class of drug that can be used to treat type 2 diabetes by reversing insulin resistance, one of the main hallmarks of the disease. While TZDs were extremely popular in the 1990's and early 2000's, they have fallen out of use among physicians in recent decades because they were discovered to cause unwanted side effects, including weight gain and excess fluid accumulation in body tissues. Now, researchers at University of California San Diego School of Medicine are exploring how to isolate the positive effects of these drugs, which could help yield new treatments that don't come with the old side effects. In a new study published in Nature Metabolism, the researchers discovered how one of the most well-known TZD drugs works at the molecular level and were able to replicate its positive effects in mice without giving them the drug itself. "For decades, TZDs have been the only drugs we have that can reverse insulin resistance, but we seldom use them anymore because of their side effects profile," said Jerrold Olefsky, M.D., a professor of medicine and assistant vice chancellor for integrative research at UC San Diego Health Sciences. "Impaired insulin sensitivity is the root cause of type 2 diabetes, so any treatment we can develop to safely restore this would be a major step forward for patients." The main driver of insulin resistance in type 2 diabetes is obesity, which currently affects more than 40 percent of Americans and in 2021 bore an annual medical cost of nearly $173 billion. In addition to causing adipose tissue (fat) to expand, obesity also causes low levels of inflammation. This inflammation causes immune cells, called macrophages, to accumulate in adipose tissue, where they can comprise up to 40 percent of the total number of cells in the tissue. When adipose tissue is inflamed, these macrophages release tiny nanoparticles containing instructions for surrounding cells in the form of microRNAs, small fragments of genetic material that help regulate gene expression. These microRNA-containing capsules, called exosomes, are released into the circulation and can travel through the bloodstream to be absorbed by other tissues, such as the liver and muscles. This can then lead to the varied metabolic changes associated with obesity, including insulin resistance. For the current study, the researchers wanted to understand how TZD drugs, which restore insulin resistance, affect this exosome system. The researchers treated a group of obese mice with rosiglitazone, a type of TZD drug. Those mice became more sensitive to insulin, but they also gained weight and retained excess fluid, known side effects of rosiglitazone. However, by isolating exosomes from the adipose tissue macrophages of the mice who had received the drug and injecting them into another group of obese mice that had not received it, the researchers were able to deliver the positive effects of rosiglitazone without transferring the negative effects. "The exosomes were just as effective in reversing insulin resistance as the drug itself but without the same side effects," said Olefsky. "This indicates that exosomes can ultimately link obesity-related inflammation and insulin resistance to diabetes. It also tells us that we may be able to leverage this system to boost insulin sensitivity." The researchers were also able to identify the specific microRNA within the exosomes that was responsible for the beneficial metabolic effects of rosiglitazone. This molecule, called miR-690, could eventually be leveraged into new therapies for type 2 diabetes. "It's likely not practical to develop exosomes themselves as a treatment because it would be difficult to produce and administer them, but learning what drives the beneficial effects of exosomes at the molecular level makes it possible to develop drugs that can mimic these effects," said Olefsky. "There's also plenty of precedent for using microRNAs themselves as drugs, so that's the possibility we're most excited about exploring for miR-690 going forward."

Company will also host a virtual analyst and investor event on November 13, 2023 PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it will present new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran (ARO-APOC3) and the ARCHES-2 study of zodasiran (ARO-ANG3) at the American Heart Association (AHA) Scientific Sessions 2023, being held in Philadelphia on November 11-13, 2023. The company will also host a virtual analyst and investor event on November 13, 2023, at 4:30 pm ET featuring key opinion leaders who will discuss these data and their relevance as potential treatments for severe hypertriglyceridemia and mixed dyslipidemia in patients with atherosclerotic cardiovascular disease (ASCVD). To register for the event, please visit: . Details about the AHA presentations are listed below. American Heart Association (AHA) Scientific Sessions 2023 – November 11-13, 2023 Title: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Triglycerides to Near Normal Levels in Patients With Severe Hypertriglyceridemia: SHASTA-2 Study Results Date/Time: November 13, 2023, 9:45 a.m. EST Presenter: Daniel Gaudet Session: Lipid Lowering via Novel Pathways Title: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Atherosclerosis-Associated Lipoproteins in Patients With Mixed Dyslipidemia: MUIR Study Results Date/Time: November 13, 2023, 1:30 p.m. EST Presenter: Christie M Ballantyne Session: Emerging Approaches to Lipid Lowering Title: ARO-ANG3, an Investigational RNAi Therapeutic, Silences the Expression of ANGPTL3 and Decreases Atherogenic Lipoproteins in Patients With Mixed Dyslipidemia: ARCHES-2 Study Results Date/Time: November 13, 2023, 1:30 p.m. EST Presenter: Robert S Rosenson Session: Emerging Approaches to Lipid Lowering The analyst and investor event will feature presentations from Arrowhead management and three experts in the treatment and management of lipid and lipoprotein disorders: Daniel Gaudet, MD, PhD, Professor of Medicine at Université de Montréal, who will discuss plozasiran in the context of the current treatment landscape for severe hypertriglyceridemia Børge Nordestgaard, MD, Professor & Chief Physician, Copenhagen University Hospital, University of Copenhagen, Denmark, who will discuss remnant cholesterol and its role in cardiovascular disease Steven Nissen, MD, Chief Academic Officer for the Heart and Vascular Institute at the Cleveland Clinic, who will discuss the potential of a cardiovascular outcomes study of plozasiran Expert Bios Daniel Gaudet, MD, PhD, is Professor of Medicine at Université de Montréal (UdeM) and leads the UdeM Community Genetic Medicine Center and its Clinical Lipidology and Rare Lipid Disorders Unit. He is currently president and scientific director of ECOGENE-21, a non-for profit organization devoted to access to innovation in precision medicine. His main clinical and academic activities aim at investigating rare or severe dyslipidemias and translating new knowledge issued from extreme phenotypes to more common forms of diseases. Over the years, he has coordinated more than 200 clinical studies involving the development of screening tools, technologies or emerging therapies for severe dyslipidemias or related disorders, in collaboration with biotechs, pharmas, or academic partners. He authored more than 320 scientific publications in peer-reviewed journals, including several tens in very highly rated Journals (NEJM, Nature Medicine, Eur Heart J, Lancet, Nature Genetics) as well as >500 scientific communications or book chapters. Børge G. Nordestgaard, MD, DMSc, is Professor & Chief Physician, Copenhagen University Hospital, University of Copenhagen, Denmark, and President-Elect European Atherosclerosis Society. Prof Nordestgaard studied and worked in Copenhagen, New York, and London. He has for more than 30 years continued his interest in the pathogenesis, diagnosis and treatment of familial hypercholesterolemia, hyperlipidemia, lipoprotein(a), atherosclerosis, diabetes and cardiovascular disease, and has written extensively on these conditions. He is chairing the Copenhagen General Population Study and is a steering committee member of the Copenhagen City Heart Study and five phase 3 cardiovascular intervention trials. Prof. Nordestgaard has supervised 74 Ph.D. students and 34 postdoctoral fellows, and has published 920 original articles and 140 reviews, book chapters, consensus statements, & editorials. His H-index is 152 in Web of Science and he is listed among the top 0.1% researchers worldwide with the most highly cited papers. Original articles include publications in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Nature, Science, Nature Genetics, British Medical Journal, Lancet Diabetes Endocrinology, Circulation, European Heart Journal, Journal of the American College of Cardiology and JAMA cardiology. Steven E. Nissen MD is Chief Academic Officer for the Heart and Vascular Institute at the Cleveland Clinic, the Lewis and Patricia Dickey Chair in Cardiovascular Medicine and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. From 2006 to 2019, he served as Chair of the Department of Cardiovascular Medicine at the Cleveland Clinic. In 2006-2007 he served as President of the American College of Cardiology (ACC), the professional society representing American cardiologists. His initial research focused on application of intravascular ultrasound (IVUS) imaging to the assessment of progression and regression of coronary atherosclerosis, conducting more than a dozen randomized controlled trials, most published in the NEJM or JAMA. More recently, he has served as Study Chairman for large global cardiovascular outcomes trials, most studying lipid modifying therapies. His contributions to scientific literature include more than 600 journal articles and 60 book chapters. He is co-author of a book for patients with heart disease, Heart411 released by Crown Books on January 31, 2012. Dr. Nissen works closely with pharmaceutical companies on the development of new therapies for cardiovascular disease, but maintains a longstanding policy of requiring companies to donate all related honoraria directly to charity so that he receives neither income, nor a tax deduction. He has also written extensively on the subject of drug safety. In 2001, he co-authored the first manuscript (JAMA) that raised concerns about the cardiovascular safety of rofecoxib (Vioxx™), which was withdrawn from the market 3 years later. In 2007, he authored a NEJM manuscript that demonstrated that the widely used diabetes drug rosiglitazone (Avandia™) raised the risk of myocardial infarction, eventually leading in 2010 to withdrawal of the drug in Europe and severe restrictions in the US. Dr. Nissen served as a member of the CardioRenal Advisory Panel of Food and Drug Administration (FDA) for 5 years, and Chairman the final year of his membership. He continues to serve as Advisor to several FDA committees as a “Special Government Employee”. In July 2008, while serving as guest member of the Endocrine and Metabolism Advisory Panel, he recommended a new approach for approval of diabetes drugs, which was ultimately adopted by the Agency in December 2008. Dr. Nissen is also known for his role in public policy discussions. He has testified in both the Senate (Health Education and Labor Committee) and House of Representatives (Energy and Commerce Committee) on Food and Drug Administration (FDA) policy. He was actively involved in discussions with Congress on the FDA Amendments Act of 2007 that added additional regulatory authority for the Agency. In 2007, Time Magazine selected Dr. Nissen as one of the world’s 100 most influential people. Beginning in 2015, he was named by Thompson-Reuters as one of the world’s most highly cited physician-scientists. A copy of the presentation materials and a webcast link for the analyst and investor event will be available on the Events and Presentations page under the Investors section of the Arrowhead website. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. 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We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc. View source version on businesswire.com: Contacts Arrowhead Pharmaceuticals, Inc. Vince Anzalone, CFA 626-304-3400 ir@arrowheadpharma.com Investors: LifeSci Advisors, LLC Brian Ritchie 212-915-2578 britchie@lifesciadvisors.com Media: LifeSci Communications, LLC Jason Braco, Ph.D. 646-751-4361 jbraco@lifescicomms.com Source: Arrowhead Pharmaceuticals, Inc. View this news release online at: