Disease Analysis: Dyslipidemia
|出版日期||內容資訊||英文 103 Pages
|疾病分析:血脂異常症 Disease Analysis: Dyslipidemia|
|出版日期: 2019年11月29日||內容資訊: 英文 103 Pages||
2018年時，推測全球整體有15億名血脂異常症患者 (20歲以上) ，2027年其數將增加到17億人。
本報告提供全球血脂異常症治療藥臨床實驗形勢與市場趨勢預測相關分析，疾病概要和流行病學的預測，目前主要治療藥 (已上市/開發中產品) 和臨床實驗的進展，目前未滿足需求和未來的市場機會，臨床實驗/市場將來相關專家的見解等資訊彙整，為您概述為以下內容。
Datamonitor Healthcare 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 cardiovascular outcomes data with label expansions.
In the hypercholesterolemia segment, the injectable PCSK9 inhibitors have struggled due to payer restrictions, but declining net pricing in the US is hoped to improve access and spur growth, though this will depend on the extent to which payers retain prior authorization. Price competition may increase with the introduction of siRNA inclisiran, but Novartis also plans to use inclisiran's more convenient maintenance dosing of every six months to pursue administration in healthcare provider offices, with medical rather than pharmacy benefit coverage, including Medicare Part B, to improve access. Inclisiran's cardiovascular outcomes trial (CVOT) is also designed to show a numerically stronger topline benefit.
Oral bempedoic acid will be limited by modest low-density lipoprotein cholesterol (LDL-C) lowering, particularly on top of statins, but good efficacy with its fixed-dose combination with ezetimibe in statin-intolerant patients will be an important addition to that high-need segment. In addition, its oral route could lead it to be preferred initially in patients failing statins +/- ezetimibe who are not too far from goal, 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. Given the large number of hypercholesterolemia patients not meeting goal, either with or without statin intolerance, if bempedoic acid's CVOT is positive, it should still be fairly successful despite its modest efficacy.
In the hypertriglyceridemia segment (including mixed dyslipidemia), positive CVOT data for the omega-3 fatty acid (FA) Vascepa, a formulation of EPA, has already started to drive substantial growth, but while the FDA is sure to grant it a label expansion for secondary prevention, it is unclear what type of primary prevention patients the FDA will include in the indication. The drug's prospects also largely depend on whether Epanova, a mixture of DHA and EPA, likewise has a positive CVOT. Epanova is likely to lag behind Vascepa if results are numerically not as strong, though it could benefit from AstraZeneca's stronger primary care presence. Depending on the details, Epanova's CVOT could also give physicians more confidence in generics of DHA/EPA when used in a high enough dose, though sponsors of other branded formulations, like CaPre, are hoping that would lead some to prefer their own formulations for other features. Vascepa's success could revive 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. This would increase competition for omega-3 FAs.
In the orphan drug segment, anti-ANGPTL3 monoclonal antibody evinacumab is expected to take share from oral Juxtapid in homozygous familial hypercholesterolemia (HoFH), due to safety and tolerability issues with the latter, but will still be limited by competition with lower-priced PCSK9 inhibitors in eligible patients, assuming evinacumab has orphan pricing. Evinacumab's HoFH trial also involved inconvenient IV dosing, but subcutaneous dosing is being studied in a Phase II trial in patients with persistent hypercholesterolemia, despite treatment even with PCSK9 inhibitors, and the drug additionally lowers triglycerides, so it could expand to other orphan dyslipidemia indications as well. The antisense drug Waylivra, which targets ApoC-III, may not be approved in the US for familial chylomicronemia syndrome due to safety issues. However, other earlier-stage antisense and RNAi drugs targeting ANGPTL3, ApoC-III, and Apo(a) may avoid these safety issues and have gained large pharma interest, including plans for a CVOT for a broader indication.
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 different dyslipidemia guidelines with varying approaches to lipid targets.
The overall likelihood of approval of a Phase I dyslipidemia asset is 10.4%, and the average probability a drug advances from Phase III is 65.4%. Dyslipidemia drugs, on average, take 8.1 years from Phase I to approval, compared to 9.8 years in the overall cardiovascular space.
There have been 15 licensing and asset acquisition deals involving dyslipidemia drugs during 2014-19. A $1,550m licensing agreement signed in 2019 between Pfizer and Akcea for AKCEA-ANGPTL3-LRx was the largest deal, though only $250m was upfront.
8 Latest key takeaways
10 Patient segmentation
11 Treatment guidelines vary across regions
11 Treatment recommendations focus on risk groups
12 Recommendations on specific classes
35 Amarin Seeks EU Fast-Track For Potential Cardiovascular Blockbuster
35 YouTube Video Suggesting Livalo Is Safer Than Other Statins Is Dinged By US FDA
37 Novartis To Pay $9.7bn For The Medicines Company
38 Pfizer Reaffirms CV Disease Commitment With Deal For Akcea's ANGPTL3 Drug
38 Deal Watch: Novartis Opts In On Lipoprotein A Candidate From Akcea
38 Asia Deal Watch: Boost For Esperion's Cholesterol Candidate As Daiichi Brought On Board
39 Novo Carves Deeper Niche Into CV Market With Staten Dyslipidemia Investment
41 Sponsors by status
42 Sponsors by phase
43 Recent events
45 Cholesterol-lowering drugs
47 Triglyceride-lowering drugs
47 Lipid-lowering and CVOT efficacy data
59 New launches and CVOT data will drive growth in the dyslipidemia market over the forecast period
59 Competition among the PCSK9 inhibitors will need to lower net prices more for the class to succeed
60 Price pressures and affordability will continue to be major factors limiting growth
64 Inclisiran for Dyslipidemia (November 16 & 18, 2019)
67 Vascepa for Dyslipidemia (November 18, 2019)
69 Vascepa for Dyslipidemia (November 14, 2019)
71 Vascepa for Dyslipidemia (November 12, 2019)
73 ARO-ANG3 for Dyslipidemia and ARO-APOC3 for Lipoprotein Lipase Deficiency (September 16, 2019)
76 Inclisiran for Dyslipidemia (September 2, 2019)
78 ETC-1002/Ezetimibe FDC for Dyslipidemia (August 29, 2019)
80 Inclisiran for Dyslipidemia (August 26, 2019)
82 Evinacumab for Dyslipidemia (August 14, 2019)
83 Vascepa for Dyslipidemia (August 8, 2019)
85 Inclisiran for Dyslipidemia (May 18, 2019)
87 ETC-1002 for Dyslipidemia (May 5, 2019)
88 ETC-1002 for Dyslipidemia (March 13, 2019)
89 CER-001 for Dyslipidemia (December 5, 2018)
90 Vascepa for Dyslipidemia (November 10, 2018)
97 Interviews with physicians at the ADA conference regarding Vascepa
97 Interview regarding PCSK9 reimbursement with a KOL from a large US payer
99 Improved options for statin-intolerant patients
99 A well-tolerated oral drug with LDL-C lowering as good as the current injectable PCSK9 inhibitors when added to a statin
99 Addressing the residual risk remaining in higher-risk patients despite well-controlled LDL-C levels
99 A way to motivate patients to stick with treatment if their lipid levels are elevated
101 Prescription information