James M. McKenney
MIAMI — Significant additional lipid lowering occurred during a 2-month period in patients assigned bempedoic acid in addition to a PCSK9 inhibitor, according to data from the first-place oral poster winner presented at the National Lipid Association Scientific Sessions.
In this phase 2 study, James M. McKenney, PharmD, FNLA, president and CEO of National Clinical Research in Richmond, Virginia, and professor emeritus at Virginia Commonwealth University School of Pharmacy in Richmond, and colleagues analyzed data from 58 patients with a fasting LDL greater than 160 mg/dL after being washed out for 6 weeks from all cholesterol-lowering therapies and before the initiation of a PCSK9 inhibitor (420 mg evolocumab [Repatha, Amgen] subcutaneously once monthly) during a run-in period and an LDL greater than 70 mg/dL before randomization. Once lipid levels were stabilized during the run-in period, patients were assigned 180 mg bempedoic acid (Esperion Therapeutics; n = 28; mean age, 62 years; 75% women) or a placebo (n = 30; mean age, 58 years; 50% women) on top of the PCSK9 inhibitor therapy.
“[Bempedoic acid] is a very unique compound,” McKenney said during the presentation. “It does inhibit ATP citrate lyase and thereby inhibits a very early conversion step in cholesterol synthesis.”
The primary endpoint was the percent change in LDL from baseline to 2 months.
At 2 months, patients assigned PCSK9 inhibitor with bempedoic acid had a 27.5% reduction in LDL compared with a 2.8% increase in patients assigned PCSK9 inhibitor with placebo (difference between groups, –30.3 percentage points; 95% CI, –41.3 to –19.2).
“The drug worked well even in spite of the LDL-C lowering power of PCSK9 inhibition therapy,” McKenney said during the presentation. “Could you ever imagine a year ago — I couldn’t, but now I can — that a PCSK9 inhibitor would be given as monotherapy in a primary prevention patient? That’s what we’re seeing here. This is a drug that may actually, and frankly will be, used in statin-intolerant patients. And if you need additional LDL-C lowering treatment after initiating it, here you see the benefit of adding bempedoic acid.”
Significant additional lipid lowering occurred during a 2-month period in patients assigned bempedoic acid in addition to a PCSK9 inhibitor, according to data from the first-place oral poster winner presented at the National Lipid Association Scientific Sessions.
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Compared with the PCSK9 inhibitor with placebo group, the PCSK9 inhibitor with bempedoic acid group had greater changes from baseline to 2 months in apolipoprotein B (―21.8% vs. 2.7%; P < .001), non-HDL (―23% vs. 1.3%; P < .001), total cholesterol (―17% vs. 0.6%; P < .001) and high-sensitivity C-reactive protein (―34.4% vs. ―1.6%; P < .05).
“There’s an anti-inflammatory effect as well as a lipid-lowering effect,” McKenney said during the presentation.
The rate of treatment-emergent adverse events were similar in patients assigned a PCSK9 inhibitor with bempedoic acid (n = 9) and those assigned PCSK9 inhibitors and placebo (n = 7).
“Addition of bempedoic acid to a PCSK9 inhibitor was well-tolerated with a safety profile similar to that observed in the PCSK9 inhibitor plus placebo group,” McKenney said during the presentation. – by Darlene Dobkowski
McKenney J. Abstract 323. Presented at: National Lipid Association Scientific Sessions; May 16-19, 2019; Miami.
Disclosures: The trial was funded by Esperion Therapeutics. McKenney reports no relevant financial disclosures.