Global Dyslipidemia Disease Analysis 2020-2027 - New Launches and CVOT Data will Drive Growth in the Dyslipidemia Market

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Mar 24, 2021, 15:00 ET

DUBLIN, March 24, 2021 /PRNewswire/ -- The "Disease Analysis: Dyslipidemia" report has been added to ResearchAndMarkets.com's offering.

The report estimates that in 2018, there were approximately 1.5 billion prevalent cases of dyslipidemia in adults aged 20 years and older worldwide, and forecasts that number to increase to 1.7 billion prevalent cases by 2027.

The dyslipidemia market is well established, and the branded segment has seen declining sales due to generics. However, the market is poised to resume steady growth due to the introduction of novel agents, improved access with price competition, and new CV outcomes data with label expansions.

In the hypercholesterolemia segment, the injectable PCSK9 inhibitors from Amgen and Regeneron have struggled due to payer restrictions. While declining net pricing in the US has improved access and growth somewhat, combined sales may only reach $1.3bn in 2020 despite a large potential market, hindered by prior authorization, even though only physician attestation may be needed.

The siRNA inclisiran, injected every six months, is slated to be approved in late 2020 and is likely to dominate the segment. Novartis plans to use inclisiran's more convenient maintenance dosing to pursue administration in healthcare provider offices, with medical rather than pharmacy benefit coverage, including Medicare Part B.

Success will depend on whether the drug can avoid prior authorization, how comfortable physicians feel about such prolonged dosing, and to what extent physicians are willing to adopt the buy-and-bill approach, which may be more suited to larger integrated delivery networks. Inclisiran's cardiovascular outcomes trial (CVOT) is also designed to show a numerically stronger top-line benefit, though the drug may well gain popularity prior to these results. The company is also open to innovative collaborations with healthcare systems outside the US, and has initiated one in the UK.

Esperion's oral Nexletol (bempedoic acid), approved in February 2020 and April 2020 in the US and Europe, respectively, has had only meager uptake so far. However, it is still early in the launch, and it is unclear how much of that is due to its relatively modest LDL-C lowering, particularly on top of statins, versus launch issues and physician inaction due to the COVID-19 crisis or lack of CVOT results, which are expected in H2 2022.

Its fixed-dose combination (FDC) with ezetimibe, Nexlizet, approved a few days after, has better efficacy and could be quite helpful in high-need statin-intolerant patients. More real-world data are needed, though, on the efficacy of the FDC in patients on higher-dose statins, due to issues in its pivotal trial. The oral route of these drugs could lead them to be preferred initially in patients failing statins +/- ezetimibe, especially those who are not too far from goal, and among primary care physicians, depending on the risk of the patient and whether the particular physician feels that reaching certain LDL-C targets is acceptable rather than driving it as low as possible.

In the US, however, both drugs' initial approvals, pending CVOT results, are in patients with atherosclerotic CV disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH). There is a large potential target market of hypercholesterolemia patients not meeting goal, either with or without statin intolerance, but much could depend on details of how Nexletol performs in its CVOT.

Novartis is also testing a monthly antisense inhibitor of lipoprotein A [Lp(a)], pelacarsen, in a pivotal CVOT. While Lp(a) contributes to the cholesterol in LDL-C measurements, it is an independent risk factor that is not reduced by statins, and the treatment could provide an important option to lower residual risk, though there is uncertainty in the outcome, as the mechanism is previously untested. Little data have been released on potential Phase II RNAi competitor AMG 890, but if it is similar to other Arrowhead drugs, it could have substantially longer dosing.

In the hypertriglyceridemia segment (including mixed dyslipidemia), a CV label expansion in the US for Amarin's omega-3 fatty acid (FA) Vascepa, a formulation of EPA, has been driving substantial growth. However, with a loss on an appeal of a US patent case in September 2020, generics are likely to enter the US soon, depending on further developments in the case. Amarin officials have claimed, though, that manufacturing issues will keep this from being a typical generic market.

On the positive side for the drug, with the failure of Epanova, a mixture of DHA and EPA, physicians may believe that pure EPA is required to reduce CV risk, which should help Vascepa against DHA/EPA generics, though details from Epanova's trial are still needed to see if there are other explanations. Vascepa's success has to some extent revived interest in triglycerides as a broader target, though its CV benefit may involve a number of other effects as well.

While fibrates have mixed CVOT data and failed to show a benefit in combination with statins in ACCORD, if the PROMINENT trial of pemafibrate is positive, it could bolster subgroup analyses of ACCORD, suggesting a benefit in patients with high triglycerides and low HDL-C. If the data are strong, it could take substantial share from Vascepa, though this could be hampered by Vascepa generics.

A number of injectable triglyceride-lowering drugs targeting ANGPTL3 and ApoC-III are being developed for a variety of indications. Drugs targeting ANGPTL3 may not lower triglycerides quite as much, but they also moderately lower LDL-C, likely through an impact on VLDL precursors and without the need for LDL receptors, as required for currently approved hypercholesterolemia agents.

Hence, Regeneron's anti-ANGPTL3 monoclonal antibody evinacumab has initially been submitted for homozygous familial hypercholesterolemia (HoFH), where it is expected to take share from oral Juxtapid due to safety and tolerability issues with the latter. However, it will still face some competition from the lower-priced PCSK9 inhibitors in patients with residual LDL receptor activity, assuming evinacumab has orphan pricing. Evinacumab's HoFH trial also involved inconvenient IV dosing, but SC dosing is being studied in a Phase II trial in patients with persistent hypercholesterolemia despite treatment even with PCSK9 inhibitors.

On the other hand, after completing a Phase IIb trial, Pfizer/Ionis's vupanorsen, an antisense targeting ANGPTL3, is planned to be studied in a pivotal CVOT in a broader mixed dyslipidemia population, where it is hoped that its impact on non-HDL-C, which includes cholesterol in triglyceride-rich particles like VLDL, as well as LDL, will improve residual risk.

Vupanorsen is also planned to reach the market earlier with a severe hypertriglyceridemia indication, including a trial against Vascepa. If vupanorsen is priced lower for a broader population and does have substantial LDL-C lowering in HoFH, it could displace evinacumab. While vupanorsen may have stronger triglyceride and LDL-C lowering, as an injectable, it could still face competition from oral pemafibrate, though the latter has a disadvantage of twice-daily dosing.

In terms of drugs targeting ApoC-III, the antisense drug Waylivra may not be approved in the US for familial chylomicronemia syndrome due to safety issues. However, Ionis's earlier-stage AKCEA-APOCIII-LRx is hoped to avoid these issues, as is vupanorsen, though it remains to be seen if they avoid them completely. Drugs targeting ApoC-III may lower triglycerides somewhat more than those targeting ANGPTL3, especially when levels are extremely high, though that remains to be proven with these next-generation drugs. However, depending on the magnitude of the difference, if vupanorsen is priced lower for a broad population, it could be used first in certain patients.

Arrowhead's ARO-APOC3 and ARO-ANG3 have numerically greater reductions in triglycerides in the most recent data than those from Ionis, but this may be due to variability in their earlier-stage, uncontrolled, smaller studies. However, they may also have the advantage of quarterly or semi-annual dosing rather than monthly, though Ionis argues that some physicians may be hesitant about such prolonged dosing in case there are safety issues. Nevertheless, this could change as more experience is gained with such drugs.

Given limited budgets for many patients, there will be indirect competition between drugs targeting LDL-C and those targeting triglycerides, if patients are eligible for both, as well as with diabetes drugs that have CV and renal benefits.

In the US, different specialties and primary care physicians may use dyslipidemia guidelines with varying approaches to lipid targets.

The overall likelihood of approval of a Phase I dyslipidemia asset is 8.9%, and the average probability a drug advances from Phase III is 62.1%. Dyslipidemia drugs, on average, take 7.6 years from Phase I to approval, compared to 10.0 years in the overall CV space.

Key Topics Covered:

OVERVIEW

Latest key takeaways

DISEASE BACKGROUND

Definition
Patient segmentation

TREATMENT

Treatment guidelines vary across regions
Treatment recommendations focus on risk groups
Recommendations on specific classes

EPIDEMIOLOGY

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS

Daiichi Sankyo Enters Europe's Cholesterol Market
Amarin Seeks EU Fast-Track For Potential Cardiovascular Blockbuster
YouTube Video Suggesting Livalo Is Safer Than Other Statins Is Dinged By US FDA

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS

Deal Watch: NewAmsterdam To Take On Amgen's Stalled CETP Inhibitor
Alnylam Secures $2bn Financing From Blackstone By Monetizing Inclisiran Royalties
Novartis To Pay $9.7bn For The Medicines Company
Pfizer Reaffirms CV Disease Commitment With Deal For Akcea's ANGPTL3 Drug

CLINICAL TRIAL LANDSCAPE

Sponsors by status
Published on 06 November 2020
Sponsors by phase
Recent events

DRUG ASSESSMENT MODEL

Cholesterol-lowering drugs
Triglyceride-lowering drugs
Lp(a)-lowering drugs
HDL-increasing drugs

MARKET DYNAMICS

FUTURE TRENDS

New launches and CVOT data will drive growth in the dyslipidemia market over the forecast period
Novel reimbursement strategy for inclisiran could salvage the PCSK9 segment
Price pressures and affordability will continue to be major factors limiting growth

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION

CaPre for Dyslipidemia (August 31, 2020)
Multiple Drugs for Dyslipidemia (August 31, 2020 and August 29, 2020)
Nexletol for Dyslipidemia (June 14, 2020)
Vupanorsen for Dyslipidemia (January 28, 2020)
Dalcetrapib for Dyslipidemia (January 27, 2020)
CaPre for Dyslipidemia (January 13, 2020)
Inclisiran for Dyslipidemia (November 16, 2019 and November 18, 2019)
Vascepa for Dyslipidemia (November 18, 2019)
Vascepa for Dyslipidemia (November 14, 2019)
Vascepa for Dyslipidemia (November 12, 2019)
ARO-ANG3 for Dyslipidemia and ARO-APOC3 for Lipoprotein Lipase Deficiency (September 16, 2019)
Inclisiran for Dyslipidemia (September 2, 2019)

KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

Interviews with physicians at the ADA conference regarding Vascepa
Interview regarding PCSK9 reimbursement with a KOL from a large US payer

UNMET NEEDS

Improved options for statin-intolerant patients
A well-tolerated oral drug with LDL-C lowering as good as the current injectable PCSK9 inhibitors when added to a statin
Addressing the residual risk remaining in higher-risk patients despite well-controlled LDL-C levels
A way to motivate patients to stick with treatment if their lipid levels are elevated

BIBLIOGRAPHY

For more information about this report visit https://www.researchandmarkets.com/r/wvso0p

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