Targeting Unmet Patient Needs
Lowering elevated LDL-C, a leading risk factor for cardiovascular disease, remains a significant unmet need
Cardiovascular disease (CVD), which results in heart attacks, strokes and other cardiovascular events, represents the number one cause of death and disability in western societies. According to American Heart Association estimates:
- 800,000 deaths in the U.S. were caused by CVD in 2013. (1)
- CVD expenses in the U.S. were $317 billion in 2011-2012; including the cost of healthcare services, medications and lost productivity. (1)
Elevated LDL-cholesterol (LDL-C or “bad cholesterol”) is a significant risk factor for cardiovascular disease. The CDC (Centers for Disease Control) through NHANES (National Health & Nutrition Examination Survey) estimates that 78 million(2) U.S. adults have elevated levels of LDL-C (also known as hypercholesterolemia). In the U.S., increasing attention has been placed on aggressive LDL-C lowering. This has led to the combination of statins with other treatments to reach LDL-C goals.
Statin therapy is effective but side effects can limit use for some patients
Statins are the cornerstone of lipid treatment today and are highly effective at lowering LDL-C. This class of drugs includes atorvastatin calcium (Lipitor®), the most prescribed LDL-C lowering drug in the world and the best-selling pharmaceutical in history:
The benefits of using statins to effectively lower LDL-C levels and improve cardiovascular outcomes are well documented. However, a significant subset of patients is unable to tolerate statins due to side effects, including:
- Muscle pain or weakness
- Increased glucose levels
- In rare and extreme cases, muscle breakdown, kidney failure and death
Current treatment options are inadequate for many patients
In 2012, the FDA warned that statins can cause hyperglycemia (an increase in blood sugar levels) and increased the risk of worsening of glycemic control and of new onset diabetes.
- Approximately 38 million U.S. adults with elevated LDL-C levels are not on an LDL-C lowering therapy.
- As many as 50% of patients stop taking statins within one year of initiating treatment. Poor statin adherence is associated with worse cardiovascular outcomes.
- Muscle pain or weakness is the most common side effect experienced by statin users and the most common cause for discontinuing therapy.
- Statins are the current standard of care for LDL-C lowering for approximately 35 million patients in the United States. However, it is estimated that approximately 10% of these patients are intolerant of statin therapy due to muscle pain or weakness associated with their use.
Additionally, patients with Heterozygous Familial Hypercholesterolemia (HeFH) or Atherosclerotic Cardiovascular Disease (ASCVD) that require additional LDL-C lowering on top of maximally tolerated statin therapy represent a high-risk patient population with an important unmet medical need. Approximately 9 million(3) patients with HeFH or ASCVD in the U.S are currently on maximally tolerated statin therapy but are unable to achieve their LDL-C treatment goal. They remain at risk for cardiovascular disease and while a number of therapeutic alternatives for HeFH and ASCVD patients are currently available or in clinical development, we believe that patients, clinicians and payors will continue to first seek once-daily, oral small molecule therapies to combine with maximally tolerated statin therapy.
Pursuing novel LDL-C lowering therapies for “statin intolerant” and residual risk individuals
Despite the success of statins for many patients, Esperion believes there is a need for a novel, safe, efficacious, oral, once-daily, small molecule LDL-C lowering therapy. To that end, we are initially pursuing the clinical development of bempedoic acid (ETC-1002) as a treatment for patients with elevated LDL-C who are not adequately controlled with current lipid-modifying therapies. Some patients with elevated LDL-C are only able to tolerate less than the lowest approved daily starting dose of a statin and can be considered “statin intolerant”. Also in development is a fixed dose combination of bempedoic acid and ezetimibe. In the first half or 2017 we plan to announce clinical and regulatory plans for development of the fixed dose combination.
(1) Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Després J-P, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jiménez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER III, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133:000-000.
(2) Mercado C, DeSimone A, Odom E et al., Prevalance of Cholesterol Treatment Eligibility and Medication Us Among Adults – United States, 2005 – 2012. MMWR Morb Mortal Wkly Rep 2015; 64:1305:1311.
(3) Esperion analysis, NHANES 2008-2012.