Angiopoietin-like protein 3 (ANGPTL3) Inhibitor - Target Population, Competitive Landscape, and Market Forecast - 2034

Key Highlights:

• Currently, only one ANGPTL3 inhibitor has received approval: Regeneron's EVKEEZA, approved in 2021 for the treatment of patients with the ultra-rare inherited form of high cholesterol, homozygous familial hypercholesterolemia (HoFH).
• ANGPTL3 inhibitors hold significant potential in cardiology and may serve as effective treatment options for various cardiac indications, including HoFH, mixed dyslipidemia (Dyslipidemias/Hyperlipidemias/Hyperlipoproteinemias), atherosclerotic cardiovascular disease (ASCVD), severe hypertriglyceridemia, and others.
• Several emerging therapies, including ALN-ANG3, Zodasiran, VERV-201, Solbinsiran, and others are in the development for cardiovascular diseases.
• Arrowhead Pharmaceuticals is expecting to begin a Phase III study in HoFH in second quarter of 2025 with Zodasiran based on availability of large amount of clinical data and an attractive dosing schedule in this population.
• Verve Therapeutics developing VERV-201 for patients with refractory hypercholesterolemia and HoFH is expecting to provide an update on the ANGPTL3 program in the second half of 2025.
• In May 2024, Arrowhead Pharmaceuticals announced the results of the Phase IIb ARCHES-2 study of zodasiran in patients with mixed hyperlipidemia. Zodasiran was associated with robust and durable reductions in triglycerides, triglyceride-rich lipoprotein remnants, and total atherogenic lipoproteins, including LDL-C.
• Unlike Antisense-Oligonucleotide Therapy (ASO) therapy, siRNA therapy uses double-stranded RNA and enables prolonged ANGPTL3 mRNA inhibition and reduced hepatic ANGPTL3 production, which supports less frequent dosing.
• ANGPTL3 inhibitors may help lower residual ASCVD risk in a wide variety of dyslipidemic patients, including those with HoFH and refractory mixed dyslipidemia.
• Arrowhead Pharmaceuticals, Eli Lilly and Company, Verve Therapeutics, and Regeneron Pharmaceuticals are actively advancing drug development programs developing ANGPTL3 inhibitors, aiming to address conditions linked to lipid metabolism and cardiovascular diseases.

DelveInsight's "Angiopoietin-like protein 3 (ANGPTL3) Inhibitor - Target Population, Competitive Landscape, and Market Forecast - 2034" report delivers an in-depth understanding of the ANGPTL3 inhibitors, historical and competitive landscape as well as its market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The ANGPTL3 Inhibitor market report provide current treatment practices, emerging therapies, market share of individual therapies, and current and forecasted 7MM ANGPTL3 Inhibitor market size from 2021 to 2034. The report also covers unmet medical needs, cost analysis, reimbursement scenarios to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2021-2034

ANGPTL3 Inhibitor Understanding

ANGPTL3 Inhibitor Overview

ANGPTL3 (angiopoietin-like 3) is a key regulator of lipoprotein metabolism, primarily expressed in the liver. It plays a critical role in lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), which contributes to low levels of triglycerides and high-density lipoprotein cholesterol (HDL-C). Genetic studies show that loss-of-function (LOF) variants in ANGPTL3 are associated with low LDL cholesterol (LDL-C), low HDL-C, and triglycerides, as well as a reduced risk of cardiovascular diseases compared to non-carriers.

The therapeutic potential of ANGPTL3 inhibitors stems from their ability to mimic LOF mutations, offering an innovative approach to treat severe hypertriglyceridemia (including familial chylomicronaemia syndrome (FCS)) and dyslipidemia. Initially developed for FCS, ANGPTL3 inhibitors also show promise in lowering LDL-C and are being explored for use in HoFH, a condition where conventional treatments often fall short.

ANGPTL3's impact on lipid metabolism is significant due to its effects on lipolysis, secretion, and uptake of lipoproteins. Mendelian randomization studies have shown that LOF variants in ANGPTL3 are linked to improved lipid profiles and a reduced risk of coronary artery disease. This mechanism is independent of LDLR, making ANGPTL3 inhibition a potential strategy for a range of lipid-related conditions.

ANGPTL3 Inhibitor Market Overview

ANGPTL3 inhibitors hold significant potential in cardiology, offering treatment options for conditions like HoFH, mixed dyslipidemia, ASCVD, and severe hypertriglyceridemia. In 2021, EVKEEZA became the first approved ANGPTL3 inhibitor, specifically for treating HoFH. Several companies, including Regeneron, Arrowhead Pharmaceuticals (Zodasiran), Verve Therapeutics (VERV-201), and Eli Lilly (Solbinsiran), are actively developing ANGPTL3 inhibitors.

Back in 2022, Vupanorsen was being developed by Pfizer and Ionis Pharmaceuticals in collaboration, but the development was withdrawn due to lack of available patients meeting the entry criteria. Moreover, the company did not provide any updates around the therapies future development plan post this event in 2022.

ANGPTL3 inhibition offers a promising approach for treating atherogenic dyslipidemia. However, the widespread use of anti-ANGPTL3 antibodies, ASOs, or siRNAs is hindered by the high costs associated with long-term therapy. For example, EVKEEZA's USD 450,000 annual cost is whooping amount for patients eventually limiting its widespread usage and accessibility.

Moreover, since there are limited treatment option for severe hypertriglyceridemia and often the patients do not respond adequately to statins, PCSK9 inhibitors, or conventional lipid-lowering therapies, ANGPTL3 inhibitors is expected to have a broader opportunity in this patient segment.

Angiopoietin-like protein 3 (ANGPTL3) Inhibitor Epidemiology

The epidemiology chapter of ANGPTL3 inhibitor in the report provides historical as well as forecasted epidemiology segmented as total cases of selected indications for ANGPTL3 inhibitor, total eligible patient pool of selected indications for ANGPTL3 inhibitor, and total treated cases of selected indications for ANGPTL3 inhibitor in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), and the United Kingdom, and Japan from 2020 to 2034.

Drug Chapters

This segment of the ANGPTL3 inhibitor report encloses a detailed profile of approved ANGPTL3 inhibitor, and all emerging inhibitors including late-stage, mid-stage and early stage development. It helps understand the clinical trial activity, inclusion criteria, primary outcome measure, pharmacological action, company agreements and collaborations, anticipated launch timeline, patent details, analyst views, and the latest news and press releases.

Marketed Therapies

EVKEEZA (Evinacumab): Regeneron Pharmaceuticals

EVKEEZA is a fully-human monoclonal antibody that binds to and blocks the function of ANGPTL3. Regeneron scientists discovered the angiopoietin gene family more than two decades ago. Human genetics research published in NEJM in 2017 by scientists from the Regeneron Genetics Center found that patients whose ANGPTL3 gene did not function properly (called a "loss-of function mutation") have significantly lower levels of key blood lipids, including LDL-C, and this is associated with a significantly lower risk of coronary artery disease. EVKEEZA was invented using Regeneron's VelocImmune technology that utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies.

In March 2023, EVKEEZA received extended approval from the US Food and Drug Administration (FDA) as an adjunct to other lipid-lowering therapies for the treatment of children aged 5 to 11 years with HoFH.

Note: Detailed current therapy profile will be provided in the ANGPTL3 Inhibitor report

Emerging Therapies

Zodasiran (ARO-ANG3): Arrowhead Pharmaceuticals

Zodasiran, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of angiopoietin-like protein (ANGPTL3), which is a hepatocyte expressed regulator of lipid and lipoprotein metabolism with multiple potential modes of action, including inhibition of lipoprotein lipase (LPL) and endothelial lipase.

Currently, there are two ongoing clinical trials evaluating zodasiran. The first trial is titled "Study of ARO-ANG3 in Adults with Mixed Dyslipidemia (ARCHES-2)", which is a double-blind, placebo-controlled Phase IIb study designed to assess the efficacy and safety of ARO-ANG3 in adults with mixed dyslipidemia. The study can be found on ClinicalTrials.gov under the identifier NCT04832971. The second trial is focused on HoFH and is titled "Study of ARO-ANG3 in Participants with HoFH (GATEWAY)". This Phase II study aims to evaluate the safety and efficacy of ARO-ANG3 in subjects with HoFH and is registered under the ClinicalTrials.gov identifier NCT05217667.

VERVE-201: Verve Therapeutics

VERVE-201 is a product candidate targeting the ANGPTL3 gene, a key regulator of cholesterol and triglyceride levels in the liver. Disrupting ANGPTL3 protein production has the potential to reduce LDL-C and remnant cholesterol levels through a mechanism distinct from that of PCSK9 inhibitors.

The therapy utilizes a proprietary GalNAc-LNP delivery system to introduce a base editor targeting the ANGPTL3 gene into the liver. In patients with HoFH, a rare genetic disorder characterized by extremely high LDL-C levels, delivering base editors via standard lipid nanoparticles (LNPs) to the liver is challenging due to the absence of low-density lipoprotein receptor (LDLR), which is crucial for LNP uptake. To address this challenge, proprietary LNPs with a GalNAc ligand have been developed, designed to bind to asialoglycoprotein receptors (ASGPR) in the liver, facilitating the uptake of the treatment in HoFH patients.

VERVE-201 is being developed to initially address two ASCVD indications with significant unmet medical needs: HoFH and refractory hypercholesterolemia. refractory hypercholesterolemia refers to patients with ASCVD who fail to achieve their medically recommended LDL-C goal despite being on maximally tolerated standard therapies.

The Pulse-1 Phase Ib clinical trial is currently underway to evaluate the safety and tolerability of VERVE-201 in adult patients with refractory hypercholesterolemia.

ANGPTL3 Inhibitor Market Outlook

The current treatment landscape for lipid disorders is dominated by well-established therapies such as statins, PCSK9 inhibitors, and fibrates. These treatments have proven effective in managing LDL cholesterol (LDL-C) and triglycerides, especially in patients with common dyslipidemia. However, there remains a significant unmet need for patients with severe forms of dyslipidemia such as HoFH and familial chylomicronaemia syndrome (FCS), conditions that often do not respond well to standard therapies.

ANGPTL3 inhibitors, emerging as a novel class of lipid-lowering agents, offer a distinct mechanism by targeting the ANGPTL3 protein, a key regulator of lipid metabolism. Unlike existing treatments, which primarily focus on modulating cholesterol or triglyceride levels through pathways like LDL receptors or lipoprotein lipase inhibition, ANGPTL3 inhibition provides an innovative approach by reducing LDL-C, triglycerides, and remnant cholesterol through a mechanism that bypasses conventional lipid pathways. Currently, EVKEEZA (evinacumab), approved by the FDA in 2021, is the first ANGPTL3 inhibitor approved for treating HoFH, and ongoing clinical trials for other ANGPTL3 inhibitors (such as Zodasiran) continue to show promise for broader applications, including refractory hypercholesterolemia. While these inhibitors hold great potential, challenges such as cost, long-term safety, and wider access to these novel treatments remain critical factors in shaping their broader adoption and market expansion. As the treatment landscape evolves, ANGPTL3 inhibitors are expected to play a vital role in addressing severe lipid disorders that current therapies cannot adequately treat.

Several key players, including Regeneron Therapeutics, Arrowhead Pharmaceuticals, Verve Therapeutics, Eli Lilly and Company, and others, are involved in developing therapies for ANGPTL3 inhibitors for various cardiology indications such as HoFH, severe hypertriglyceridemia, ASCVD, and others, respectively. Overall, this is an exciting new class of technology with great potential for development. The maturation of current studies over the next few years will lead to a better understanding of ANGPTL3 inhibitors and define their role in cardiology.

ANGPTL3 Inhibitor Therapies Uptake

This section focuses on the peak shares allotment, uptake rate of potential approved and emerging ANGPTL3 inhibitor based on a detailed conjoint analysis of safety, efficacy, order of entry and route of administration expected to be launched or already launched in the market during 2021-2034.

ANGPTL3 Inhibitor Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics.

The presence of numerous therapies under different stages is expected to generate immense opportunity for ANGPTL3 Inhibitor market growth over the forecasted period.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for ANGPTL3 inhibitor therapies.

KOL Views

To keep up with current and future market trends, we take Industry Experts' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on ANGPTL3 inhibitor evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, therapies uptake, along challenges related to accessibility.

DelveInsight's analysts connected with 20+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as Division of Cardiology, Department of Medicine, Montefiore Medical Center, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, and others.

Their opinion helps understand and validate current and emerging therapy treatment patterns or ANGPTL3 Inhibitor market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

"ANGPTL3 inhibitors represent a promising advancement in lipid management, particularly for patients with severe genetic lipid disorders like HoFH and refractory hypercholesterolemia. These therapies offer a novel approach to lowering LDL-C, triglycerides, and remnant cholesterol in ways that current treatments cannot. While early clinical data is promising, long-term safety and accessibility will be critical to their broader adoption in clinical practice."

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and conjoint analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Market Access and Reimbursement

Reimbursement may be referred to as the negotiation of a price between a manufacturer and payer that allows the manufacturer access to the market. It is provided to reduce the high costs and make the essential therapies affordable. Health Technology Assessment (HTA) plays an important role in reimbursement decision-making and recommending the use of a therapies. These recommendations vary widely throughout the seven major markets, even for the same therapies.

In the US healthcare system, both Public and Private health insurance coverage are included. Also, Medicare and Medicaid are the largest government-funded programs in the US. The major healthcare programs including Medicare, Continuing Medical Education (CME) program, the Children's Health Insurance Program (CHIP), and the state and federal health insurance marketplaces are overseen by the Centers for Medicare & Medicaid Services (CMS). Other than these, Pharmacy Benefit Managers (PBMs), and third party organizations that provide services, and educational programs to aid patients are also present.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Key Updates on Angiopoietin-like protein 3 (ANGPTL3) Inhibitor

• In February 2025, Arrowhead Pharmaceuticals announced in conference call that company is planning to begin a Phase III study in HoFH next quarter with zodasiran.
• In November 2024, Verve Therapeutics announced that the first participant was dosed with VERVE-201 in its Pulse-1 open-label Phase Ib clinical trial. The Pulse-1 clinical trial is designed to evaluate the safety and tolerability of VERVE-201 administration in adult patients with refractory hypercholesterolemia who require additional lowering of LDL-C despite treatment with maximally tolerated standard of care therapies, potentially including PCSK9 inhibitors.
• In May 2024, Arrowhead Pharmaceuticals presented new phase II data of zodasiran in patients with mixed hyperlipidemia at European Atherosclerosis Society 92nd Congress and simultaneously published in the New England Journal of Medicine.

This list is not exhaustive, will be provided in the final report

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of the ANGPTL3 inhibitor, explaining its mechanism, and therapies (current and emerging).
• Comprehensive insight into the competitive landscape, and forecasts, the future growth potential of treatment rate, and therapies uptake, have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late, mid-stage and early stage therapies will impact the current landscape.
• A detailed review of the ANGPTL3 inhibitor therapies in the cardiology market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM therapies outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis, conjoint analysis, expert insights/KOL views, and treatment preferences that help shape and drive the 7MM ANGPTL3 Inhibitor market.

ANGPTL3 Inhibitor Report Insights

• ANGPTL3 Inhibitor Targeted Patient Pool
• Therapeutic Approaches
• ANGPTL3 Inhibitor Pipeline Analysis
• ANGPTL3 Inhibitor Market Size and Trends
• Existing and future Market Opportunities
• Cost Assumptions and Analogue assessment

ANGPTL3 Inhibitor Report Key Strengths

• 10 years Forecast
• The 7MM Coverage
• Key Cross Competition
• Therapies Uptake and Key Market Forecast Assumptions
• Pricing trends

ANGPTL3 Inhibitor Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT and Conjoint analysis)

Key Questions:

• What was the total market size of ANGPTL3 inhibitor, the market size by therapies, market share (%) distribution, and what would it look like in 2034? What are the contributing factors for this growth?
• Which drug is going to be the largest contributor in 2034?
• Which is the most lucrative market for ANGPTL3 inhibitor?
• What are the pricing variations among different geographies for approved therapy?
• How the reimbursement landscape for ANGPTL3 inhibitor evolved since the first one was approved? Do patients have any access issues that are driven by reimbursement decisions?
• What are the risks, burdens, and unmet needs of treatment with ANGPTL3 inhibitor?
• What are the key factors hampering the growth of the ANGPTL3 inhibitor market?
• What key designations have been granted to ANGPTL3 inhibitors?
• What are the country-specific accessibility issues of expensive, recently approved therapy?

Reasons to buy:

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the ANGPTL3 inhibitor market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis, and ranking of indication-wise current and emerging therapies under the conjoint analysis section to provide visibility around leading indications.
• Highlights of access and reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.