Esperion Announces Publication of Phase 3 Data for Bempedoic Acid in the Journal of Clinical Lipidology
Esperion Announces Publication of Phase 3 Data for Bempedoic Acid in the Journal of Clinical Lipidology
April 13, 2022
Analysis of pooled Phase 3 data demonstrated 26.5% reduction vs. placebo in LDL-C from bempedoic acid monotherapy and 39.2% reduction vs. placebo in LDL-C from bempedoic acid and ezetimibe fixed-dose combination in patients not taking statins
ANN ARBOR, Mich., April 13, 2022 (GLOBE NEWSWIRE) -- Esperion (NASDAQ: ESPR) today announced the publication of data from a pooled analysis of patients enrolled in four Phase 3 bempedoic acid studies in the Journal of Clinical Lipidology.
The paper, “Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials,” discussed a pooled analysis of data from patients enrolled in four Phase 3 bempedoic acid studies, 12 to 52 weeks in duration, who were not taking concomitant statins (n=394), and a Phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (n=33). The objective of the studies was to assess the LDL-C lowering effect of bempedoic acid in patients not taking statins measured as percent change in LDL-C from baseline to week 12.
“Although statins are the mainstay of lipid-lowering treatment, 1 out of 5 individuals with a clinical indication for statin therapy are unable to take a daily statin because of side effectsi and more than half (45–70%) of patients discontinue their statin therapy within 1–2 years after initiationii,” said JoAnne Foody, M.D., FACC, FAHA, chief medical officer of Esperion. “The results from this pooled analysis evaluating bempedoic acid monotherapy and a fixed-dose combination with ezetimibe in patients not taking statins suggest that bempedoic acid could be an effective and generally well-tolerated option for these patients, but further study is warranted. Esperion’s ongoing global CLEAR Outcomes trial, evaluating the effects of bempedoic acid on statin-intolerant patients, will expand the existing body of knowledge on lipid management for this underserved patient group and offer key insights into managing LDL-C without the use of statins.”
The results of the analysis demonstrated that in patients with hypercholesterolemia who are unable to take statins, bempedoic acid monotherapy resulted in a 26.5% mean reduction in LDL-C (p<0.001) versus placebo and a fixed-dose combination of bempedoic acid with ezetimibe resulted in a 39.2% mean reduction in LDL-C versus placebo, significantly greater than with bempedoic acid or ezetimibe alone (p<0.001). Therapy was generally well-tolerated by patients and any muscle-related disorders were comparable to those observed in the placebo group. Treatment-emergent adverse events leading to discontinuation of study drug occurred at a rate of 32.8 per 100 Patient Years (PY) and 24.3 per 100 PYs with bempedoic acid and placebo, respectively. The most common reason for discontinuation of study drug was myalgia with an incidence of 5.8 per 100 PY for patients treated with bempedoic acid and 10.6 per 100 PY for patients receiving placebo.
Please see Important Safety information for Bempedoic Acid (Nexletol) and Bempedoic Acid plus Ezetimibe (Nexlizet) below.
NEXLETOL and NEXLIZET are indicated as adjuncts to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Limitations of Use: The effect of NEXLETOL and NEXLIZET on cardiovascular morbidity and mortality has not been determined.
IMPORTANT SAFETY INFORMATION
Contraindications: NEXLETOL has no contraindications. NEXLIZET is contraindicated in patients with a known hypersensitivity to ezetimibe tablets. Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria have been reported with ezetimibe.
Warnings and Precautions: Hyperuricemia: Bempedoic acid, a component of NEXLETOL and NEXLIZET, may increase blood uric acid levels. Hyperuricemia may occur early in treatment and persist throughout treatment, and may lead to the development of gout, especially in patients with a history of gout. Assess uric acid levels periodically as clinically indicated. Monitor for signs and symptoms of hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.
Tendon Rupture: Bempedoic acid is associated with an increased risk of tendon rupture or injury. In clinical trials, tendon rupture occurred in 0.5% of patients treated with bempedoic acid versus 0% of patients treated with placebo, and involved the rotator cuff (the shoulder), biceps tendon, or Achilles tendon. Tendon rupture occurred within weeks to months of starting bempedoic acid. Tendon rupture may occur more frequently in patients over 60 years of age, patients taking corticosteroid or fluoroquinolone drugs, patients with renal failure, and patients with previous tendon disorders. Discontinue NEXLETOL or NEXLIZET at the first sign of tendon rupture. Avoid NEXLETOL and NEXLIZET in patients who have a history of tendon disorders or tendon rupture.
Adverse Reactions: In NEXLETOL clinical trials, the most commonly reported adverse reactions were upper respiratory tract infection, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. Reactions reported less frequently, but still more often than with placebo, included benign prostatic hyperplasia and atrial fibrillation.
In the NEXLIZET clinical trial, the most commonly reported adverse reactions observed with NEXLIZET, but not observed in clinical trials of bempedoic acid or ezetimibe, a component of NEXLIZET, and occurring more frequently than with placebo, were urinary tract infection, nasopharyngitis, and constipation.
Adverse reactions reported in clinical trials of ezetimibe, and occurring at an incidence greater than with placebo, included upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza. Other adverse reactions reported in postmarketing use of ezetimibe included hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria; erythema multiforme; myalgia; elevated creatine phosphokinase; myopathy/rhabdomyolysis; elevations in liver transaminases; hepatitis; abdominal pain; thrombocytopenia; pancreatitis; nausea; dizziness; paresthesia; depression; headache; cholelithiasis; cholecystitis.
Drug Interactions: Simvastatin and Pravastatin: Concomitant use with bempedoic acid results in increased concentrations and increased risk of simvastatin or pravastatin-related myopathy. Use of either NEXLETOL or NEXLIZET with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.
Cyclosporine: Caution should be exercised when using NEXLIZET and cyclosporine concomitantly due to increased exposure to both ezetimibe and cyclosporine. Monitor cyclosporine concentrations in patients receiving NEXLIZET and cyclosporine. In patients treated with cyclosporine, the potential effects of the increased exposure to ezetimibe from concomitant use should be carefully weighed against the benefits of alterations in lipid levels provided by NEXLIZET.
Fibrates: Coadministration of NEXLIZET with fibrates other than fenofibrate is not recommended. Fenofibrate and ezetimibe may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected in a patient receiving NEXLIZET and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.
Cholestyramine: Concomitant use of NEXLIZET and cholestyramine decreases ezetimibe concentration. This may result in a reduction of efficacy. Administer NEXLIZET either at least 2 hours before, or at least 4 hours after, bile acid sequestrants.
Lactation and Pregnancy: It is not recommended that NEXLETOL or NEXLIZET be taken during breastfeeding. Discontinue NEXLETOL or NEXLIZET when pregnancy is recognized, unless the benefits of therapy outweigh the potential risks to the fetus. Based on the mechanism of action of bempedoic acid, NEXLETOL and NEXLIZET may cause fetal harm.
Patients or their physicians are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 or report side effects to Esperion at 833-377-7633 (833 ESPRMED).
Esperion works hard to make our medicines easy to get, easy to take and easy to have. We discover, develop, and commercialize innovative medicines and combinations to lower cholesterol, especially for patients whose needs aren’t being met by the status quo. Our entrepreneurial team of industry leaders is inclusive, passionate and resourceful. We are singularly focused on managing cholesterol so you can improve your health easily. Esperion commercializes NEXLETOL® (bempedoic acid) and NEXLIZET® (bempedoic acid and ezetimibe) Tablets and is the leader in the development of convenient oral, once-daily non-statin LDL-cholesterol lowering drugs for patients with high levels of bad cholesterol. For more information, please visit www.esperion.com and follow us on Twitter at www.twitter.com/EsperionInc.
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding, future operations, commercial products, clinical development including the timing, designs and plans for the CLEAR Outcomes study and its results, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Esperion’s actual results to differ significantly from those projected, including, without limitation, the impact of the ongoing COVID-19 pandemic on our business, revenues, results of operations and financial condition, the net sales, profitability, and growth of Esperion’s commercial products, clinical activities and results, supply chain, commercial development and launch plans, and the risks detailed in Esperion’s filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Esperion disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.
i Saeed B, Wright E, Evans W, et al. PS1-45: prevalence of statin intolerance in a high-risk cohort and management strategies in contemporary cardiology. Clin Med Res. 2013;11:136.
ii Banach M, Stulc T, Dent R, et al. Statin non-adherence and residual cardiovascular risk: there is need for substantial improvement. Int J Cardiol. 2016;225:184–196.