SPPARM stands for selective peroxisome proliferator-activated receptor alpha modulators.
Pemafibrate (Parmodia) is a selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) currently licensed in Japan for the management of dyslipidaemia and hypertriglyceridaemia.
Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor which has a key role in transcriptional regulation of lipoprotein metabolism, specifically fatty acid transport and beta-oxidation, as well as vascular inflammation (1). Activation of the PPARα receptor either activates or represses target genes involved in lipid metabolism, including APOA1, APOA2, APOA5, APOC3 and LPL, with downstream effects including reduced very low-density lipoprotein (VLDL) production and lowering of TG (1). Modulation of the core PPARα ligand (fibrate) resulted in pemafibrate, with enhanced binding to PPARα, and potentially improved selectivity and potency over current fibrates (2,3).
In phase II/III trials in Japanese and European patients with elevated TG with or without type 2 diabetes, treatment with pemafibrate 0-2 mg or 0-4 mg daily reduced TG by ~50%, remnant cholesterol (by up to 80%), and apoCIII (by ~50%) (4). Treatment with pemafibrate also ameliorated the atherogenic lipoprotein profile, reducing the proportion of small and very small LDL particles, and increasing small and very small HDL particles (5).
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- Bougarne N, Weyers B, Desmet SJ, Deckers J, Ray DW, Staels B, et al. Molecular actions of PPARα in lipid metabolism and inflammation. Endocr Rev 2018;39:760–802. PUBMED https://pubmed.ncbi.nlm.nih.gov/30020428/
- Fruchart JC. Selective peroxisome proliferator-activated receptor α modulators (SPPARMα): the next generation of peroxisome proliferator-activated receptor α-agonists. Cardiovasc Diabetol. 2013;12:82. PUBMED https://pubmed.ncbi.nlm.nih.gov/23721199/
- Yamashita S, Masuda D, Matsuzawa Y. Pemafibrate, a new selective PPARalpha Modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases. Curr Atheroscler Rep 2020;22(1):5. PUBMED https://pubmed.ncbi.nlm.nih.gov/31974794/
- Fruchart JC, Santos RD, Aguilar-Salinas C, et al. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation. Cardiovasc Diabetol 2019 Jun 4;18(1):71. PUBMED https://pubmed.ncbi.nlm.nih.gov/31164165/
- Ishibashi S, Yamashita S, Arai H, et al. Effects of K-877, a novel selective PPARalpha modulator (SPPARMalpha), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis 2016;249:36-43. PUBMED https://pubmed.ncbi.nlm.nih.gov/27062408/