Esperion Announces Positive Top-Line Results from Pivotal Phase 3 Bempedoic Acid / Ezetimibe Combination Pill Study
— Bempedoic Acid / Ezetimibe Combo Pill Achieved an Additional 35%
LDL-C Lowering in Patients on Maximally Tolerated Statins —
— 35% LDL-C Lowering Provides Potential for More Than 6 Million U.S. Patients to Reach
LDL-C Levels of 70 mg/dL —
— Bempedoic Acid / Ezetimibe Combo Pill Appeared to be as Safe and Well-Tolerated as Ezetimibe Alone —
— Provided an Additional 34% hsCRP Reduction —
— Bempedoic Acid / Ezetimibe Combo Pill Achieved an Additional 43% LDL-C lowering in Patients Considered Statin Intolerant (post-hoc analysis) —
— Conference Call and Webcast on
This pivotal Phase 3, 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
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;
“I’m pleased to see the positive safety and tolerability profile of the bempedoic acid / ezetimibe fixed-dose combination pill which was similar to that of ezetimibe alone,” said
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.
“These pivotal study results of the bempedoic acid / ezetimibe combination pill are highly compelling. As Lipid Management experts, we know that 35 percent LDL-C lowering could help more than six million ASCVD and/or HeFH patients on maximally tolerated statins achieve LDL-C levels of 70mg/dL or less, an elusive LDL-C target for most patients today. With a reduction in hsCRP as a key marker for CV risk reduction based on CANTOS, our 34 percent hsCRP reduction is truly exceptional,” said
Topline data from Study 2 (1002-047) are now expected in
Design of Pivotal Phase 3 Study 3 (1002-053)
The 12-week, pivotal Phase 3 randomized, double-blind, parallel group, multicenter study to evaluate the efficacy and safety of bempedoic acid 180 mg / ezetimibe 10 mg combination pill compared to bempedoic acid, ezetimibe or placebo in high-risk patients with ASCVD and/or heterozygous familial hypercholesterolemia or with multiple risk factors for ASCVD being treated with maximally tolerated statins. The study was conducted at 78 sites in
Conference Call and Webcast Information
Esperion's Lipid Management Team will host a conference call and webcast today,
About Esperion's Global Pivotal Phase 3 LDL-C Lowering Program
Esperion initiated its global, pivotal, Phase 3 clinical development program in
- Two pivotal studies evaluating bempedoic acid (Studies 1 & 2) in 3,009 patients with ASCVD on maximally-tolerated statins, with top-line results reported in
May 2018, and expected in October 2018, respectively;
- Two pivotal studies evaluating bempedoic acid (Studies 3 & 4) in 614 patients with ASCVD, or at a high risk for ASCVD, considered statin intolerant, with top-line results reported in May and
March 2018, respectively;
- One pivotal study evaluating the bempedoic acid / ezetimibe combination pill (053 Study) in 382 patients with ASCVD, or at high risk for ASCVD, on maximally tolerated statins, with top-line results reported in this press release.
Esperion plans to submit New Drug Applications (NDAs) to the
Bempedoic Acid / Ezetimibe Combination Pill
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. Phase 3 data demonstrated that this safe and well tolerated combination results in a 35 percent lowering of LDL-C, and a 34 percent reduction in high sensitivity C-reactive protein (hsCRP).
With a targeted mechanism of action, bempedoic acid is a first-in-class, complementary, orally available, once-daily ATP Citrate Lyase (ACL) inhibitor that reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. Similar to statins, bempedoic acid also reduces hsCRP, a key marker of inflammation associated with cardiovascular disease. Completed Phase 2 and Phase 3 studies conducted in almost 4,800 patients, and approximately 2,900 patients treated with bempedoic acid, have produced LDL-C lowering results of up to 30 percent as monotherapy, 35 percent in combination with ezetimibe on maximally tolerated statins, 48 percent in combination with ezetimibe as monotherapy, and an additional 20 percent on maximally tolerated statins.
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. The company initiated a global cardiovascular outcomes trial (CVOT) to assess the effects of bempedoic acid on the occurrence of major cardiovascular events in patients with, or at high risk for, cardiovascular disease (CVD) who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered "statin intolerant." The CVOT — known as Cholesterol Lowering via Bempedoic Acid, an ACL-inhibiting Regimen (CLEAR) Outcomes — is an event-driven, global, randomized, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients with hypercholesterolemia and high CVD risk at up to 1,000 sites in approximately 30 countries.
Esperion's Commitment to Patients with Hypercholesterolemia
High levels of LDL-C can lead to a build-up of fat and cholesterol in and on artery walls (known as atherosclerosis), potentially leading to cardiovascular events, including heart attack or stroke. In the U.S., 78 million people, or more than 20 percent of the population, have elevated LDL-C; an additional 73 million people in
Esperion's mission as the
Esperion is the
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the regulatory approval pathway for the bempedoic acid / ezetimibe combination pill and bempedoic acid and the therapeutic potential of, clinical development plan for, the bempedoic acid / ezetimibe combination pill and bempedoic acid, including Esperion's timing, designs, plans and announcement of results regarding its global pivotal Phase 3 clinical development program for bempedoic acid and the bempedoic acid / ezetimibe combination pill, Esperion's timing and plans for submission of NDAs to the
Source: Esperion Therapeutics, Inc.