Bempedoic Acid / Ezetimibe Fixed Dose Combination

Esperion is also pursuing development of a once-daily, oral, LDL-C–lowering, fixed-dose, combination pill of 180 mg of bempedoic acid and 10 mg of ezetimibe. This non-statin, combination oral therapy is Esperion’s lead product in development, to be used in combination with other lipid-lowering therapies for patients with primary hyperlipidemia who need additional LDL-C lowering.

Bempedoic acid plus ezetimibe fixed-dose combination is designed to have complementary mechanisms of action.

  • Bempedoic acid inhibits cholesterol synthesis via ACL inhibition, primarily in the liver.
  • Ezetimibe blocks gastrointestinal cholesterol absorption via NPC1L1 (Niemann-Pick C1-Like 1) inhibition, reducing cholesterol delivery to the liver.

These complementary mechanisms are designed to result in LDL receptor upregulation and increased LDL-C clearance from the bloodstream.

Based on feedback received from the FDA, Esperion initiated a single, pivotal, Phase 3 bridging study (1002-053) evaluating bempedoic acid plus ezetimibe fixed-dose combination 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 is intended to support approval for an LDL-C–lowering indication in both the U.S. and Europe.

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