Developing IQVIA’s positions on key trends in the pharma and life sciences industries, with a focus on EMEA.
Learn moreDeveloping IQVIA’s positions on key trends in the pharma and life sciences industries, with a focus on EMEA.
Learn moreDeveloping IQVIA’s positions on key trends in the pharma and life sciences industries, with a focus on EMEA.
Learn moreDeveloping IQVIA’s positions on key trends in the pharma and life sciences industries, with a focus on EMEA.
Learn more"We strive to help improve outcomes and create a healthier, more sustainable world for people everywhere.
LEARN MOREReimagine clinical development by intelligently connecting data, technology, and analytics to optimize your trials. The result? Faster decision making and reduced risk so you can deliver life-changing therapies faster.
Research & Development OverviewGenerate and disseminate evidence that answers crucial clinical, regulatory and commercial questions, enabling you to drive smarter decisions and meet your stakeholder needs with confidence.
REAL WORLD EVIDENCE OVERVIEWElevate commercial models with precision and speed using AI-driven analytics and technology that illuminate hidden insights in data.
COMMERCIALIZATION OVERVIEWOrchestrate your success across the complete compliance lifecycle with best-in-class services and solutions for safety, regulatory, quality and medical information.
COMPLIANCE OVERVIEWWhen your destination is a healthier world, making intelligent connections between data, technology, and services is your roadmap.
TECHNOLOGIES OVERVIEWExplore our library of insights, thought leadership, and the latest topics & trends in healthcare.
DISCOVER INSIGHTSAn in-depth exploration of the global healthcare ecosystem with timely research, insightful analysis, and scientific expertise.
SEE LATEST REPORTSBy making intelligent connections between your needs, our capabilities, and the healthcare ecosystem, we can help you be more agile, accelerate results, and improve patient outcomes.
LEARN MOREBuilding on a rich history of developing AI for healthcare, IQVIA AI connects the right data, technology, and expertise to address the unique needs of healthcare. It's what we call Healthcare-grade AI.
LEARN MOREThe IQVIA Human Data Science Cloud is our unique capability designed to enable healthcare-grade analytics, tools, and data management solutions to deliver fit-for-purpose global data at scale.
LEARN MOREThe IQVIA Innovation Hub connects start-ups with the extensive IQVIA network of assets, resources, clients, and partners. Together, we can help lead the future of healthcare with the extensive IQVIA network of assets, resources, clients, and partners.
LEARN MOREIQVIA Decentralized Trials deliver purpose-built clinical services and technologies that engage the right patients wherever they are. Our hybrid and fully virtual solutions have been used more than any others.
LEARN MOREEmpowering patients to personalize their healthcare and connecting them to caregivers has the potential to change the care delivery paradigm.
LEARN MOREOur mission is to accelerate innovation for a healthier world. Together, we can solve customer challenges and improve patient lives.
LEARN MORECareers, culture and everything in between. Find out what’s going on right here, right now.
LEARN MORE"Improving human health requires brave thinkers who are willing to explore new ideas and build on successes. Unleash your potential with us.
SEARCH JOBSPrimary dyslipidemia is a genetic metabolic condition characterized by abnormalities of the lipid profile constituted by cholesterol, triglycerides (TG), and lipoprotein of five major classes: chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Dysregulation of lipoprotein and lipid metabolism is the greatest contributor of the development of atherosclerosis and coronary artery disease.
Some patients using standard statin therapy alone or in combination with other lipid lowering therapies are not able to achieve their LDL cholesterol (LDL-C) reduction goal, particularly patients with homozygous familial hypercholesterolemia. Hence, there is a need for alternative and adjunct therapeutic strategies for these patients and gene silencing approaches by antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) have proven to be effective treatment options.
Familial hypercholesterolemia is caused by mutations in the following three genes relevant to plasma LDL metabolism: low-density lipoprotein cholesterol receptor (LDLR), apolipoprotein B100 (ApoB-100) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Because gene silencing achieves inhibition of the production of selected proteins, specific therapies have been developed exploiting the target biology and knowledge of the lipid metabolism underlying the disorder. The targets investigated thus far, and the antisense therapies developed against these targets according to Pipeline Intelligence will be reviewed.
ApoB-100 is an essential protein for the production of pro-atherogenic lipoproteins, namely VLDL, LDL and lipoprotein A. High levels of ApoB-100, especially associated with the higher LDL levels, is a primary driver for cardiovascular disease.
Apolipoprotein (a) [Apo(a)] which is bound to ApoB-100 via a disulfide bond, leads to the formation of lipoprotein (a) [Lp(a)], a cholesterol-rich LDL-like particle. Lp(a) is a key driver for cardiovascular disease due to its association with an increased risk of coronary heart disease. Therefore, drugs that can lower Lp(a) levels by targeting Apo(a) are being developed.
Apolipoprotein CIII (ApoCIII) is a 79-amino acid glycoprotein synthesized in the liver that has a role in the regulation of TG levels. ApoCIII is present on TG rich lipoproteins, such as VLDL. ApoCIII impairs clearance of these particles by inhibition of the enzyme lipoprotein lipase (LPL). It is also known to delay clearance of TG-rich lipoproteins. ApoCIII may also play a role in the activity of hepatic lipase and assembly and secretion of TG-rich lipoproteins. Therefore, ApoCIII plays a key role directly and indirectly in the pathogenesis of atherosclerosis and is being explored as a therapeutic target for hypertriglyceridemia.
PCSK9 promotes the degradation of LDL receptors and consequently increases levels of LDL-C in serum and eventually premature cardiovascular disease. Conversely, loss-of-function mutations are accompanied by decreased levels of LDL-C and a decreased risk of cardiovascular disease.
Angiopoietin-like 3 protein (ANGPTL3) is a liver synthesized inhibitor of lipoprotein lipase and endothelial lipase. ANGPTL3 inhibition has been shown to lower serum LDL, serum and liver TG levels.
The landscape of antisense therapies for lipid disorders according to Pipeline Intelligence is presented in Figure 1.
Despite the use of first-line statin therapy, many patients with familial hypercholesterolemia fail to achieve optimal reductions of LDL-C levels or are unable to tolerate statins. ASOs and siRNAs have proven to be effective as adjunct or alternate therapies in these patients.
Register to the INNsight Newsletter for regular patent, pipeline and conference updates.