TY - JOUR
T1 - A Head-to-Head Comparison of a Free Fatty Acid Formulation of Omega-3 Pentaenoic Acids Versus Icosapent Ethyl in Adults With Hypertriglyceridemia
T2 - The ENHANCE-IT Study
AU - Maki, Kevin C.
AU - Bays, Harold E.
AU - Ballantyne, Christie M.
AU - Underberg, James A.
AU - Kastelein, John J. P.
AU - Johnson, Judith B.
AU - Ferguson, James J.
N1 - Funding Information: This study was funded by Matinas BioPharma, Inc. (Bedminster, NJ). Funding Information: Dr Maki has received research grants from Matinas BioPharma, Inc. and Pharmavite, and served as a consultant for Matinas BioPharma, Inc., Acasti Pharma Inc., New Amsterdam Pharma, Pharmavite, and 89bio. Dr Bays has received research grants from Matinas BioPharma, Inc. and Amarin and served as a consultant for Matinas BioPharma, Inc., Acasti Pharma Inc., and Amarin. Dr Ballantyne has received research grants from Abbott Diagnostics, Akcea, Amgen, Arrowhead, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, National Institutes of Health, American Heart Association, and American Diabetes Association, and has served as a consultant for Matinas BioPharma, Inc., Amarin, Abbott Diagnostics, Althera, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Merck, New Amsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Underberg has served as a consultant for Matinas BioPharma, Inc. and Amgen, and is on the speaker’s bureaus for Amgen, Regeneron, Amryt, Alexion, and Esperion. Dr Kastelein served as a consultant for Matinas BioPharma, Inc. and AstraZeneca, and has ownership in New Amsterdam Pharma. J. B. Johnson is a former employee of Matinas BioPharma, Inc., and current employee of New Amsterdam Pharma. Dr Ferguson is an employee of Matinas BioPharma, Inc. Publisher Copyright: © 2022, American Heart Association Inc.. All rights reserved.
PY - 2022/3/15
Y1 - 2022/3/15
N2 - BACKGROUND: MAT9001 is an omega-3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA-ethyl esters [EE]), EPA+DPA-FFA previously showed en-hanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very– low fat diet. This trial compared pharmacodynamic responses and plasma omega-3 levels following twice daily dosing, with meals, of EPA+DPAFFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. METHODS AND RESULTS: This open-label, randomized, 2-way crossover trial, with 28-day treatment periods separated by ≥28-day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150– 499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA-FFA and EPA-EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively (P=not significant). EPA+DPA-FFA reduced least squares geometric mean high-sensitivity C-reactive protein by 5.8%; EPA-EE increased high-sensitivity C-reactive protein by 8.5% (P=0.034). EPA+DPA-FFA increased least squares geometric mean plasma EPA, DPA, and total omega-3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA-EE of 692%, 140%, and 165% (all P<0.001). EPA+DPA-FFA increased docosahexaenoic acid by 1.7%; EPA-EE decreased docosahexaenoic acid by 3.3% (P=0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. CONCLUSIONS: EPA+DPA-FFA raised plasma EPA, DPA, and total omega-3 significantly more than did EPA-EE. EPA+DPA-FFA also reduced triglycerides and high-sensitivity C-reactive protein without increasing low-density lipoprotein cholesterol. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.
AB - BACKGROUND: MAT9001 is an omega-3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA-ethyl esters [EE]), EPA+DPA-FFA previously showed en-hanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very– low fat diet. This trial compared pharmacodynamic responses and plasma omega-3 levels following twice daily dosing, with meals, of EPA+DPAFFA and EPA-EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. METHODS AND RESULTS: This open-label, randomized, 2-way crossover trial, with 28-day treatment periods separated by ≥28-day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150– 499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA-FFA and EPA-EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively (P=not significant). EPA+DPA-FFA reduced least squares geometric mean high-sensitivity C-reactive protein by 5.8%; EPA-EE increased high-sensitivity C-reactive protein by 8.5% (P=0.034). EPA+DPA-FFA increased least squares geometric mean plasma EPA, DPA, and total omega-3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA-EE of 692%, 140%, and 165% (all P<0.001). EPA+DPA-FFA increased docosahexaenoic acid by 1.7%; EPA-EE decreased docosahexaenoic acid by 3.3% (P=0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. CONCLUSIONS: EPA+DPA-FFA raised plasma EPA, DPA, and total omega-3 significantly more than did EPA-EE. EPA+DPA-FFA also reduced triglycerides and high-sensitivity C-reactive protein without increasing low-density lipoprotein cholesterol. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04177680.
KW - docosapentaenoic acid
KW - eicosapentaenoic acid
KW - hypertriglyceridemia
KW - omega-3 fatty acids
KW - triglycerides
UR - http://www.scopus.com/inward/record.url?scp=85126830484&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/JAHA.121.024176
DO - https://doi.org/10.1161/JAHA.121.024176
M3 - Article
C2 - 35232215
SN - 2047-9980
VL - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 6
M1 - e024176
ER -