Esperion Therapeutics (ESPR) shares plunged more than 30% in pre-market trading on Tuesday after the company provided an update on the clinical development and regulatory path for lead product candidate bempedoic acid, its candidate for lowering "bad" cholesterol in patients intolerant of statins. Investors have been mainly disappointed with the news that the FDA has refused to clarify a regulatory pathway for the LDL-C indication citing potential changes in their view of LDL-C lowering as a surrogate endpoint and the possibility of a shift in the future standard-of-care for statin-intolerant patients with elevated LDL-C. ESPR noted that if lowering LDL-C is no longer a surrogate endpoint for approval, it will still submit a New Drug Application (NDA) for a CV disease risk reduction claim by 2022. This means a significant delay in potential approval in the U.S. However, there some positive news as well. ESPR said that a global pivotal Phase 3 trial to evaluate the safety and efficacy is expected to start in the fourth quarter. A cardiovascular outcomes study is also expected to commence in the fourth quarter. The company believes that the study timelines will support a MAA in Europe in 2019 for patients with elevated LDL-C.