Vupanorsen

- Study met its primary endpoint, achieving statistically significant reduction in non-high density lipoprotein cholesterol (non-HDL-C) compared to placebo at all doses tested - Key secondary endpoints were met including statistically significant reductions in triglycerides and angiopoietin-like-3 (ANGPTL3) at all doses tested - Pfizer is continuing to review the findings to determine next steps regarding future development [24-November-2021] CARLSBAD, Calif., Nov. 24, 2021 /PRNewswire/ -- Ionis Pharmaceuticals, Inc., (NASDAQ: IONS) today announced that Pfizer has provided an update on the Phase 2b study of vupanorsen, formerly IONIS-ANGPTL3-LRx. Vupanorsen is an investigational antisense therapy being developed for indications in cardiovascular (CV) risk reduction and severe hypertriglyceridemia (SHTG). In the dose-ranging study in subjects with elevated non-HDL-C and triglycerides (TG), the study met its primary endpoint, achieving a statistically significant reduction in non-HDL-C at all doses tested at 24 weeks, compared to placebo. In addition, subjects treated with vupanorsen achieved statistically significant reductions in TG and ANGPTL3 at all dose levels at 24 weeks, compared to placebo. "We were pleased to see statistically significant reductions in the primary endpoint, non-HDL-cholesterol, and in the secondary endpoint of triglycerides at all doses tested. The topline results of the Phase 2b study also showed that vupanorsen dose-dependently lowered its target, angiopoietin-like 3. Pfizer is continuing to review the findings to determine next steps regarding future development. We look forward to the full data set being presented at a medical meeting next year," said Sotirios "Sam" Tsimikas, M.D., vice president of global cardiovascular development and cardiovascular franchise lead at Ionis. The most common adverse events were injection site reactions, which occurred most often in the highest vupanorsen dose group. The most common laboratory abnormalities were increases in liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and were seen primarily at the higher doses. There were no Hy's Law cases in vupanorsen-treated subjects, and no meaningful changes in bilirubin. Certain doses of vupanorsen were associated with increases from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton density fat fraction at Week 24, compared to placebo. No subject had a confirmed platelet count abnormality or a confirmed reduction in the estimated glomerular filtration rate. There were no serious adverse events (SAEs) related to treatment. The incidence of SAEs was similar between active and placebo groups. The global multicenter, double-blind, placebo-controlled, dose-ranging Phase 2b study TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70) enrolled 286 participants (≥ 40 years old) with dyslipidemia, defined in this study as participants with elevated non-HDL-C (≥ 100 mg/dL) and TG (150-500 mg/dL), who are receiving a stable dose of a statin. Participants received either 80 mg, 120 mg or 160 mg every 4 weeks, or 60 mg, 80 mg, 120 mg or 160 mg every two weeks via subcutaneous injection. The study was designed to assess the efficacy, safety, tolerability and pharmacokinetics of vupanorsen, and the primary endpoint was percent change from baseline in non-HDL-C at week 24. About vupanorsen Vupanorsen is an investigational antisense therapy discovered by Ionis and being developed by Pfizer for potential indications in CV risk reduction and SHTG. Vupanorsen is designed to reduce the production of ANGPTL3 protein, a key regulator of triglyceride and cholesterol metabolism, in the liver. This antisense therapy was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery that people with a genetic deficiency in ANGPTL3 have reduced levels of LDL-C and TG, and a decreased risk of diabetes and CV disease.i In a Phase 1 study, subjects treated with vupanorsen achieved robust, dose-dependent reductions in ANGPTL3, TG, LDL-C, non-HDL-C and total cholesterol with a favorable safety and tolerability profile.ii In a Phase 2a study, vupanorsen met the primary endpoint of significant reductions in TG levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability profile.iii In November 2019, Pfizer licensed vupanorsen from Ionis in a worldwide exclusive agreement. About Ionis Pharmaceuticals, Inc. For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing the standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry leading neurological and cardiometabolic franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming one of the most successful biotechnology companies. To learn more about Ionis visit or follow us on Twitter @ionispharma. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, and the therapeutic and commercial potential of vupanorsen and Ionis' technologies and products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2020, and the most recent Form 10-Q quarterly filing, which are on the SEC. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. References i JAMA Cardiol. 2018 Oct 1;3(10):957-966. ii N Engl J Med. 2017 Jul 20;377(3):222-232. iii Eur Heart J. 2020 Oct 21;41(40):3936-3945. Company Codes: NASDAQ-NMS:IONS

Los Angeles, USA, June 09, 2021 (GLOBE NEWSWIRE) -- Lipodystrophy Pipeline | A Clinical Trials Analysis Report | DelveInsight The companies with their Lipodystrophy drug candidates in the most advanced stage (Phase III stage) include Ionis Pharmaceuticals, soon drifting the Lipodystrophy Pipeline landscape. DelveInsight's "Lipodystrophy Pipeline Insight" report provides comprehensive insights about 10+ companies and 10+ pipeline drugs in the Lipodystrophy pipeline landscapes. It comprises Lipodystrophy pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Lipodystrophy therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Lipodystrophy pipeline products. Some of the key takeaways from the Lipodystrophy Pipeline Report Get an overview of pipeline landscape @ Lipodystrophy Clinical Trials Analysis Lipodystrophy is a medical problem where there is an abnormal distribution of fat in the body. The condition is also characterised by a lack of circulating leptin, which may lead to osteosclerosis. Currently, there is no specific treatment, which will permanently replace adipose tissue. The Lipodystrophy treatment is focused on managing metabolic abnormalities to prevent complications and cosmetic appearance. Lipodystrophy Emerging Drugs IONIS-APOCIII-LRx, formerly known as AKCEA-APOCIII-LRx, is a ligand-conjugated (LICA) investigational antisense medicine designed to prohibit the production of apoC-III for patients who are at risk of condition due to increased triglyceride levels. ApoC-III is a protein produced in the liver that maintains triglyceride metabolism in the blood. The drug is currently being investigated in the Phase III stage of development to treat patients with Hyperlipoproteinaemia and Lipodystrophy. The U.S. FDA and European Medicines Agency have also granted the drug with the Orphan drug designation. Vupanorsen is an investigational antisense therapy founded by Ionis Pharmaceuticals and co-developed by Ionis and its subsidiary Akcea Therapeutics. Vupanorsen has been created using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform to prohibit the production of angiopoietin-like 3 (ANGPTL3) protein, which a vital regulator of triglyceride and cholesterol metabolism in the liver. Pfizer has started a Phase 2b study of vupanorsen in statin-treated patients with elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs). REGN4461 is a leptin receptor (LEPR) agonist for lipodystrophy and obesity which is being developed by Regeneron Pharmaceuticals. It is currently in the Phase II stage of development. It is administered intravenously or subcutaneously. CGT2 was licensed from Lipigon Pharmaceuticals 2019; CombiGene expanded its scope to include metabolic diseases. The project's initial goal is to develop a gene therapy treatment for partial lipodystrophy, a very rare disease that today completely lacks adequate treatment. CGT2 is currently in the Preclinical stage of development. For further information, refer to the detailed report @ Lipodystrophy Pipeline Therapeutics Scope of Lipodystrophy Pipeline Drug Insight Key Questions regarding Current Lipodystrophy Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customised pipeline report @ Lipodystrophy Drugs Pipeline Report Related Reports DelveInsight's Lipodystrophy - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. DelveInsight' s HIV-associated Lipodystrophy - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. Lipodystrophy Market Research Report deliver an in-depth understanding of the Lipodystrophy Market Size, Share, Trends, Pipeline Therapies, Key Companies, and Epidemiology Forecast in the 7MM. DelveInsight's Lipodystrophy - Epidemiology Forecast 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology of Lipodystrophy in the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan. DelveInsight's Liposarcoma Market Insights, Epidemiology and Market Forecast - 2030 report provides a depth understanding of historical and forecasted epidemiology. DelveInsight's Necrobiosis Lipoidica (NL) - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. About DelveInsightDelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. It also provides Healthcare Consulting services comprising credible market analysis that will help accelerate the business growth and overcome challenges with a practical approach.