Topline results for Phase III bempedoic acid / ezetimibe combination pill study (1002-053).

Esperion announced positive top-line results from the pivotal Phase III bempedoic acid / ezetimibe combination pill study (1002-053). This trial was a randomized, double-blind, parallel group study conducted to evaluate the efficacy and safety of the bempedoic acid 180 mg / ezetimibe 10 mg combination pill compared to bempedoic acid, ezetimibe or placebo in patients treated with maximally tolerated statins.

This pivotal Phase III, four-arm study design including a primary endpoint of LDL-C lowering, study statistics and an abbreviated 505(b)(2) regulatory pathway were discussed and agreed to with the FDA in 2017. The study included 382 high-risk patients taking maximally tolerated statins who required additional LDL-C lowering and met its key efficacy endpoints, including: On-treatment analysis LDL-C lowering of 35 percent for the combination pill at 12 weeks (p<0.001) compared to 3 percent for placebo, 24 percent for ezetimibe 10 mg (eze) and 20 percent for bempedoic acid 180 mg (ba); in the intent to treat analysis, ldl-c lowering was 32 percent for the combination pill compared to 3 percent for placebo (p><0.001), 21 percent for eze (p><0.001) and 18 percent for ba (p><0.001); reduction of 34 percent for the fdc in high-sensitivity c-reactive protein (hscrp), an important marker of the underlying inflammation associated with cardiovascular disease, compared with an increase in placebo of 4 percent and reductions of 20 percent for ba and 9 percent for eze.>

In a post-hoc analysis of patients considered statin intolerant, the combination pill LDL-C lowering was 43 percent in the on-treatment analysis compared to a one percent increase for placebo;Safety and Tolerability of Combination Pill Over 12 Weeks- In this 12-week study, the bempedoic acid / ezetimibe combo pill was observed to be safe and well-tolerated. The results showed no clinical differences between the FDC, BA, EZE and placebo patient groups in the occurrence of: Serious adverse events (SAEs) with 8 percent, 6 percent, 9 percent and 2 percent, respectively. No SAEs were considered to be related to study medication; Discontinuations due to AEs with 7 percent, 8 percent, 9 percent, and 4 percent, respectively; No elevations in liver function tests (ALT/AST) of greater than three times the upper limit of normal, repeated and confirmed were observed.

Comment: Topline data from Study 2 (1002-047) are now expected in October 2018 (prior guidance end-of-September 2018). NDAs will be submitted during the first quarter of 2019.