For statin-intolerant patients, what's next?
Despite their blockbuster status and distinction as the world's most widely prescribed class of drugs, statins may not be the best option for all patients with elevated low density lipoprotein (LDL) cholesterol levels.
Esperion Therapeutics saw an opening for new LDL-lowering agents and is pouncing on the opportunity with its novel oral treatment bempedoic acid.
Though recent research suggests the benefits of statins outweigh side effects, clinicians still believe there is a subset of patients who cannot tolerate them, says Dr. Paul Thompson, director of cardiology at Hartford Hospital. The main side effect of statins is muscle pain, though incidents of liver damage, increased risk of type 2 diabetes, and neurological issues have been reported.
Bempedoic acid is a first-in-class ACL inhibitor that lowers elevated levels of LDL-C by up-regulating the LDL receptor. Esperion president and CEO Tim Mayleben says bempedoic acid sets itself apart from statins by working in only the liver and not all tissues, thereby reducing the potential for muscle-related side effects.
Mayleben is quick to sing the praises of statins, but notes they're not well-suited for everyone. “Almost 90% of patients can tolerate a statin without severe side effects. But due to hypercholesterolemia, a large underserved population remains,” he explains.
Phase I and II studies conducted in more than 700 patients showed bempedoic acid lowered LDL by 30% as monotherapy, about 50% in combination with ezetimibe, and an incremental 24% when added to stable statin therapy. Its Phase III LDL-C lowering clinical development program will include patients with hypercholesterolemia on any statin at any dose.
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According to Chung I. Choi, senior director, atherosclerosis at CardioVascular Resource Group, positive results from Phase III trials could mean better uptake for bempedoic acid over PCSK9 inhibitors due to its lower cost and oral administration. Even so, she predicts bempedoic acid settling into the third-in-line treatment spot behind statins and generic ezetimibe.
For all the excitement around bempedoic acid, some experts contend it faces a challenging path to market. As a result of an FDA policy snag, a potential 2018 approval may be pushed back to 2022. The agency has indicated changes in their view of LDL-C lowering as a surrogate endpoint and a possible shift in the standard-of-care for statin intolerant patients with elevated LDL-C levels has changed bempedoic acid's timeline.
In response, Esperion has initiated the CLEAR Outcomes trial to assess the effects of bempedoic acid in statin-intolerant patients at high risk of CV disease. However, Choi says the agent's efficacy is modest and running a CVOT study large enough to please the FDA may be beyond what Esperion can afford.