- |||||||||| Review, Journal: Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia. (Pubmed Central) - Jan 12, 2025
These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3)...Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia and other ANGPTL3 inhibitors may prove be useful to reduce triglycerides in T2D.
- |||||||||| Review, Journal: An up-to-date review of emerging biologic therapies for hypercholesterolemia. (Pubmed Central) - Jan 3, 2025
The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Trial completion: ARCHES-2: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (clinicaltrials.gov) - Nov 7, 2024
P2, N=204, Completed,
Advances in antisense oligonucleotide technology, especially the GalNAc delivery platform, show promise for personalized lipid management, though challenges such as cost and safety concerns remain. Active, not recruiting --> Completed
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Journal: Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia. (Pubmed Central) - Sep 11, 2024
P2
In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks. (Funded by Arrowhead Pharmaceuticals; ARCHES-2 ClinicalTrials.gov number, NCT04832971.).
- |||||||||| Review, Journal: RNA interference therapy in cardiology: will new targets improve therapeutic goals? (Pubmed Central) - Aug 27, 2024
Zilebesiran, which targets hepatic angiotensinogen mRNA, has demonstrated a dose-related reduction in serum angiotensinogen levels, thereby lowering blood pressure in patients with systemic arterial hypertension...In the future, larger studies will provide insights into improvements in cardiovascular outcomes, long-term safety and broader applications in the general population. This review highlights the historical timeline of the development of siRNA-based drugs, their clinical indications, potential side-effects and future perspectives.
- |||||||||| Review, Journal: Advances in Dyslipidaemia Treatments: Focusing on ApoC3 and ANGPTL3 Inhibitors. (Pubmed Central) - Feb 1, 2024
The antisense oligonucleotide (ASO) vupanorsen targeting ANGPTL3 was less effective in reducing LDL-C in patients with moderate hypertriglyceridaemia and its development has been discontinued but the small interfering RNA (siRNA) ARO-ANG3 is being investigated in Phase 2 studies...Olezarsen is an N-acetylgalactosamine-conjugated ASO targeting apoC3 which appears as effective as volanesorsen without the risk of thrombocytopaenia and is undergoing Phase 3 trials. ARO-APOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Phase classification: ARCHES-2: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (clinicaltrials.gov) - Jan 16, 2024
P2, N=204, Active, not recruiting,
ARO-APOC3 is an siRNA targeting apoC3 that is currently being investigated in Phase 3 studies. Phase classification: P2b --> P2
- |||||||||| ARO-ANG3 / Arrowhead, vupanorsen (AKCEA-ANGPTL3-LRx) / Ionis, Pfizer
Journal: Angiopoietin-like 3 inhibition and the liver: less is more? (Pubmed Central) - Nov 3, 2023
An alternative explanation may relate to off-target effects of vupanorsen, which have a molecule- and/or platform-specific origin. For intrahepatic strategies, highly potent ANGPTL3 inhibition will for now require special attention for liver safety.
- |||||||||| Review, Journal: Updates in Small Interfering RNA for the Treatment of Dyslipidemias. (Pubmed Central) - Oct 4, 2023
Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.
- |||||||||| Review, Journal: Updates in Drug Treatment of Severe Hypertriglyceridemia. (Pubmed Central) - Aug 29, 2023
siRNA targeting APOC3 and ANGPTL3, namely ARO-APOC3 and ARO-ANG3, are also promising for the treatment of sHTG. However, the ultimate clinical goal of any sHTG treatment, the decrease in the risk of AP, has not been definitively achieved till now by any pharmacotherapy, either approved or in development.
- |||||||||| Review, Journal: Recent Advances in Gene Therapy for Familial Hypercholesterolemia: An Update Review. (Pubmed Central) - Nov 27, 2022
With gene editing technologies, such as CRISPR-Cas 9 and meganuclease, completing animal experiments in mice or cynomolgus monkeys and demonstrating lasting lipid-lowering effects, patients with FH are expected to reach a permanent cure in the future. (4) Gene therapy is being widely used for the lipid-lowering treatment of FH patients and has shown excellent therapeutic promise, but the current delivery efficiency, economic burden, immunogenicity and the precision of gene therapy can be further optimized.
- |||||||||| Journal: Safety and efficacy of therapies for chylomicronemia. (Pubmed Central) - Aug 11, 2022
Potential utility of antagonists of angiopoietin-like protein 3 (ANGPTL3) such as evinacumab and the siRNA ARO-ANG3 in subtypes of chylomicronemia remains to be defined...However, these treatments are still investigational. Further study of their efficacy and safety in patients with both rare FCS and more common multifactorial chylomicronemia is needed.
- |||||||||| Review, Journal: The promising novel therapies for familial hypercholesterolemia. (Pubmed Central) - Jul 17, 2022
Further study of their efficacy and safety in patients with both rare FCS and more common multifactorial chylomicronemia is needed. While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Enrollment closed, Trial completion date, Trial primary completion date: ARCHES-2: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (clinicaltrials.gov) - Jul 1, 2022
P2b, N=204, Active, not recruiting,
While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine. Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Nov 2024 | Trial primary completion date: Oct 2022 --> Aug 2022
- |||||||||| Journal: Advances in the care of lipodystrophies. (Pubmed Central) - Apr 26, 2022
However, these treatments are not yet approved for use in lipodystrophy. Further study of their efficacy and safety in this patient population is needed.
- |||||||||| Evkeeza (evinacumab) / Regeneron, Ultragenyx, ARO-ANG3 / Arrowhead
Journal: Inhibition of angiopoietin-like 3 for the management of severe hypercholesterolemia. (Pubmed Central) - Feb 24, 2022
Not yet recruiting --> Recruiting With the promise of these emerging novel therapeutics directed against ANGPTL3 on the horizon, achieving acceptable target LDL-C levels in HoFH without the need for lipoprotein apheresis may finally be a realistic goal and we can anticipate a decrease in cardiovascular morbidity and mortality in these difficult to treat patients.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Trial completion: Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients (clinicaltrials.gov) - Sep 21, 2021
P1, N=93, Completed,
With the promise of these emerging novel therapeutics directed against ANGPTL3 on the horizon, achieving acceptable target LDL-C levels in HoFH without the need for lipoprotein apheresis may finally be a realistic goal and we can anticipate a decrease in cardiovascular morbidity and mortality in these difficult to treat patients. Active, not recruiting --> Completed
- |||||||||| Review, Journal: ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets. (Pubmed Central) - Sep 10, 2021
ANGPTL3 and Apo C-III targeting agents have demonstrated striking lipid-lowering effects in recent clinical trials; however, more thorough safety and efficacy data are required. Here, we evaluate the role of ANGPLT3 and Apo C-III in lipid metabolism, present the latest clinical advances targeting those molecules, and outline the remaining scientific challenges on residual lipid-associated cardiovascular risk.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Enrollment open: ARCHES-2: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (clinicaltrials.gov) - May 27, 2021
P2b, N=180, Recruiting,
Here, we evaluate the role of ANGPLT3 and Apo C-III in lipid metabolism, present the latest clinical advances targeting those molecules, and outline the remaining scientific challenges on residual lipid-associated cardiovascular risk. Not yet recruiting --> Recruiting
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Enrollment closed, Trial completion date, Trial primary completion date: Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients (clinicaltrials.gov) - Dec 10, 2020
P1, N=94, Active, not recruiting,
Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting | Trial completion date: May 2020 --> May 2021 | Trial primary completion date: May 2020 --> May 2021
- |||||||||| Waylivra (volanesorsen) / Novartis, evinacumab (REGN1500) / Regeneron, ARO-ANG3 / Arrowhead
Review, Journal: Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia. (Pubmed Central) - Aug 18, 2020
Multiple ANGPLT3 inhibitors (evinacumab, IONIS-ANGPTL3-L, ARO-ANG3) effectuate TG reductions up to 70% with concomitant potent reduction in all other apoB containing lipoprotein fractions. We expect these therapeutics to become players in the treatment for (especially) severe HTG in the near future.
- |||||||||| zodasiran (ARO-ANG3) / Arrowhead
Trial completion date, Trial primary completion date: Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients (clinicaltrials.gov) - Sep 12, 2019
P1, N=94, Recruiting,
ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Trial completion date: Dec 2019 --> May 2020 | Trial primary completion date: Dec 2019 --> May 2020
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