Pharmacokinetics of MAT9001, an Omega-3 Fatty Acid Medication, Compared with Eicosapentaenoic Acid Ethyl Esters in Hypertriglyceridemic Subjects

Synopsis MAT9001 (Matinas BioPharma Inc., Bedminster, NJ) is a novel investigational omega‐3 fatty acid (OM3) medication containing predominantly eicosapentaenoic (EPA) and docosapentaenoic (DPA) acids under development as an adjunct to diet for the treatment of severe hypertriglyceridemia (≥500 mg/dL). Purpose This randomized, crossover trial compared the bioavailability of MAT9001 and an OM3 EPA ethyl ester (EPA‐EE) agent (Vascepa; Amarin Pharmaceuticals, Bedminster, NJ) after single‐ and multiple‐dosing under fed (low‐fat) conditions in men and women with fasting triglycerides (TG) 200–400 mg/dL at screening without lipid‐altering therapy, or TG 200–350 mg/dL if on stable‐dose statin monotherapy. Methods Forty‐two subjects received 4 g/day MAT9001 and EPA‐EE in random order, while housed in a clinical research unit for 14‐day treatment periods, separated by ≥35 days of wash‐out. Baseline values were averaged from pre‐dose samples drawn on days −1 and 0. On‐treatment values were determined from plasma samples drawn on days 0 (single‐dose) and 13 (multiple‐dose). Total EPA, DPA, docosahexaenoic (DHA) and heneicosapentaenoic (HPA) acids were measured in plasma by a liquid chromatography–tandem mass spectrometry method using isotopically substituted OM3 compounds as internal standards. Total OM3 was calculated as the sum of molar concentrations of total EPA, DPA, DHA, and HPA for each time point. Systemic exposure (area under the curve [AUC]) and peak exposure (C max ) were calculated based on the measured and baseline‐adjusted concentrations. The log‐transformed AUC and C max were analyzed using a statistical model corresponding to a 2‐way crossover design. Results After single dose administration, MAT9001 was superior to EPA‐EE for systemic bioavailability of EPA, DPA and total OM3, with baseline‐adjusted AUC and maximal concentrations approximately 8‐fold higher. Following multiple dose administration, the bioavailability over the dosing interval (AUC tau ) and the steady state C max were approximately 6‐fold higher for MAT9001 compared to EPA‐EE for both total OM3 and EPA. At steady state conditions, AUC tau and maximal plasma concentration for DPA were 4‐fold and 5‐fold higher, respectively, for MAT9001 as compared to EPA‐EE. Each of these comparisons achieved a statistical significance with p<0.0001. Conclusion These results suggest that MAT‐9001, comprised predominantly of EPA and DPA, dosed with low‐fat meals exhibits significantly increased bioavailability after both single and multiple dose administrations, as compared to EPA‐EE. This significantly higher systemic absorption of fatty acids from MAT9001 relative to EPA‐EE has also been shown to produce greater TG reduction. Further research is underway to investigate the pharmacodynamic effects of MAT9001 and to evaluate possible implications for cardiovascular risk. Support or Funding Information Funded by Matinas BioPharma Inc., Bedminster, NJ