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    Home > Biochemistry News > Biotechnology News > Up to 75% reduction in triglyceride levels 4 innovative therapies announce the latest clinical results.

    Up to 75% reduction in triglyceride levels 4 innovative therapies announce the latest clinical results.

    • Last Update: 2020-10-01
    • Source: Internet
    • Author: User
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    Arrowhead Pharmaceuticals Arrowhead announced the results of two RNAi candidate therapies in Phase 1/2 clinical trials at the ESC Annual Meeting.
    ARO-APOC3 is an RNAi therapy that targets the mRNA of lipoprotein C3 (apolipoprotein C3, APOC3).
    APOC3 protein plays an important role in regulating lipid metabolism by inhibiting liver cells from removing lipoprotein particles rich in triglycerides, leading to elevated levels of triglycerides (TGs) and very low-density lipoproteins (VLDLs) in the blood, while hdl-lipoprotein cholesterol (HDL-C, "good" cholesterol) levels decrease.
    ARO-APOC3 is designed to improve HDL levels while lowering the levels of TG and VLDL by lowering the expression levels of the APOC3 protein.
    ARO-APOC3 (Photo: Arrowhead) Arrowhead reported on the performance of blood lipids after receiving two doses of ARO-APOC3 injected with two doses of ARO-APOC3 in phase 1/2 clinical trials at the ESC Annual Meeting.
    test results found that two doses of ARO-APOC3 injections at intervals of 4 weeks reduced the volunteers' APOC3 protein levels by up to 94% (50 mg dose) and that the effect lasted for 16 weeks.
    50 mg dose, two doses of ARO-APOC3 reduced triglyceride levels in volunteers by 75% and lasted up to 16 weeks.
    ARO-APOC3 significantly reduces triglyceride (TG) levels in healthy volunteers (Photo: Arrowhead)) while ARO-APOC3 can reduce low-density lipoprotein cholesterol (LDL-C) in volunteers by 25% and increase HDL-C levels by 75%.
    the company's other RNAi therapy, ARO-ANG3, targets mRNA that encodes angiogen-like protein 3 (ANGPTL3).
    ANGPTL3 is an emerging target in the field of blood lipid reduction.
    human genetics studies have shown that mutations in the inorcability ANNGPTL3 gene cause lower levels of LCL-C, VLDL-C, HDL-C, and TG, and reduce the risk of cardiovascular disease in people who carry these gene mutations.
    , Regeneron's single-resistance therapy evinacumab, which targets ANNGPTL3, has been approved as a priority review by the FDA for patients with pure hetero-family hyperlipidemia (HoFH).
    in phase 1/2 clinical trials, the levels of ANGPTL3 protein in healthy volunteers treated with two doses of ARO-ANG3 decreased by up to 96% (300 mg dose) at intervals of 4 weeks.
    , the group's triglyceride levels dropped by as much as 67 percent and LDL-C levels by 50 percent.
    ARO-ANG3 significantly reduced triglyceride levels in healthy volunteers (Photo: Arrowhead)Ionis/Akcea for the same APOC3 and ANGPTL3 targets, and Ionis' Akcea Therapeutics company also announced the clinical results of phase 2 of two ASO therapies at the ESC Annual Meeting.
    ASO therapy is similar to RNAi therapy in that they both target the mRNA that causes the disease, except that ASO therapy relies on RNase H to degrade the complex produced by combining ASO with mRNA to inhibit the production of pathogenic proteins.
    Ionis Antonytherapy Illustration (Photo: Ionis official website) Ionis and Akcea developed vupanorsen using Ionis' Liss Lission Antisumin (LICA) technology platform to target ASO therapies that lower levels of ANGPTL3 protein in the liver.
    In a randomized double-blind, placebo-controlled dose-increment Phase 2 clinical trial, a total of 105 patients with hyperlipidemia, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) received different doses of vupanorsen, or placebo.
    trial results showed a significant decrease in dose dependence on the level of triglycerides on an empty stomach, with an average decrease of 44 per cent compared to placebo in patients treated at vupanorsen at a dose of 80 mg (once every four weeks).
    in this group, VLDL levels decreased by 38%, total cholesterol levels decreased by 19%, and non-HDL cholesterol levels decreased by 18%, all of which were statistically significant.
    Pfizer has been awarded the development rights to the in-research therapy and will be responsible for the next step in clinical development.
    the company is expected to be treated with statins, but phase 2b clinical trials will be conducted in patients with non-HDL-C levels and triglyceride levels that remain high.
    developed jointly by Ionis and Akcea, AKCEA-APOCIII-L (Rx), an antonymical oligonucleotide therapy targeting APOC3, also reached major and critical secondary clinical endpoints in Phase 2 clinical trials.
    In this randomized double-blind, placebo-controlled dose-increment Phase 2 clinical study, patients diagnosed with cardiovascular disease or high-risk hyperlipidemia with cardiovascular disease were treated with AKCEA-APOCIII-L (Rx) or placebo.
    trial results showed that the patient group receiving the highest dose of treatment had a 62 percent lower level of triglycerides on an empty stomach than the placebo group, and 91 percent had a lower triglyceride level than 150 mg/dL after 6 months of treatment.
    , these patients had a 60 percent lower level of VLDL cholesterol and a 42 percent increase in HDL cholesterol.
    , cardiovascular disease remains one of the leading causes of death worldwide.
    the risk of cardiovascular disease, it is important not only to control LDL cholesterol, but also to reduce triglycerides and other harmful lipoprotein indicators.
    the results presented at the ESC Annual Meeting by Arrowhead and Ionis/Akcea show that RNAi and ASO therapies, as innovative treatment models, can effectively target innovative targets for regulating lipid metabolism.
    , one potential advantage of RNAi and ASO therapies is that one treatment may provide long-term efficacy, and patients may only need one injection every 4-6 months to effectively control blood lipid levels.
    this simple treatment model has been validated in several Phase 3 clinical trials targeting PCSK9's RNAi therapy inclisiran.
    is also expected to become the first FDA-approved RNAi therapy to reduce LDL-C levels in patients this year.
    ASO and RNAi therapies as innovative treatment models, most of the diseases initially approved for treatment are rare.
    , however, with advances in the development of ASO and RNAi therapies, the types of diseases currently being treated are beginning to develop towards a large number of popular diseases.
    clinical trial results, presented at the EASL International Liver Congress and ESC Annual Meeting, further demonstrate the potential of oligonucleotide therapy, which targets RNA, to treat diseases in the general public.
    it is true that these in-study therapies still require Phase 3 clinical trials to further test their efficacy and safety, and we wish them a smooth development process for the benefit of more patients at an early date."
    : s1. Arrowhead Presents Positive New Phase 1/2 Clinical Data on Cardiometabolic Candidates ARO-APOC3 and ARO-ANG3 at European Society of Cardiology Congress 2020. Retrieved August 31, 2020, from .2 Positive Phase 2 Clinical Data of Vupanorsen (AKCEA-ANGPTL3-L(Rx)) Presented at ESC Congress 2020. Retrieved August 31, 2020, from #assets_43_177-3:28 (3) Positive Phase 2 Clinical Data of AKCEA-APOCIII-L (Rx) Presented at ESC Congress 2020. Retrieved August 31, 2020, from.
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