Bempedoic Acid / Ezetimibe Fixed Dose Combination

Esperion is also pursuing development of a complementary, convenient, consistent, once-daily, oral LDL-C lowering fixed dose combination pill of 180 mg of bempedoic acid and 10 mg of ezetimibe. This highly effective non-statin combination pill is the Company’s lead product in development to significantly reduce elevated levels of LDL-C in patients who are not adequately treated with current lipid-modifying therapies, including those patients considered statin intolerant.

Through the complementary mechanisms of action of inhibition of cholesterol synthesis (bempedoic acid) and inhibition of cholesterol absorption (ezetimibe), the bempedoic acid / ezetimibe combination pill is our lead, non-statin, orally available, once-daily, LDL-C lowering therapy. Inhibition of ATP Citrate Lyase (ACL) by bempedoic acid reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. Inhibition of Niemann-Pick C1-Like 1 (NPC1L1) by ezetimibe results in reduced absorption of cholesterol from the gastrointestinal tract, thereby reducing delivery of cholesterol to the liver, which in turn upregulates the LDL receptors.

Based on feedback received from the FDA, Esperion initiated a single pivotal Phase 3 bridging study (1002-053) evaluating the bempedoic acid / ezetimibe combination pill in 382 patients with ASCVD, or at high risk for ASCVD, taking maximally-tolerated statin therapy. Top-line results were reported in August 2018. The Phase 3 bridging study will support approval for an LDL-C lowering indication in both the U.S. and Europe.

Esperion announced positive topline results of 1002-053 in August 2018. The combination pill of bempedoic acid and ezetimibe provided an additional 35 percent LDL-C lowering and a 34 percent hsCRP reduction. In patients considered statin intolerant (not taking any statin background therapy), the combination pill lowered LDL-C by an additional 43%. In this study, the combo pill appeared to be as safe and well-tolerated as ezetimibe alone.

In tandem with the NDA submission for bempedoic acid, the company plans to submit a NDA for an LDL-C lowering indication for the bempedoic acid / ezetimibe combination pill through the abbreviated 505(b)(2) pathway by the first quarter of 2019. The company also expects to submit a Marketing Authorization Application (MAA) for an LDL-C lowering indication for the bempedoic acid / ezetimibe combination pill, consistent with the European Medicines Agency’s “Guideline on Clinical Development of Fixed Combination Medicinal Products”.