Pemafibrate (Parmodia®) is a novel, highly selective peroxisome proliferator-activated receptor (PPAR)-α modulator (SPPARM). It acts by binding to PPAR-α and regulating the expression of target genes that modulate lipid metabolism, thereby decreasing plasma triglyceride levels and increasing high-density lipoprotein cholesterol levels. Developed by Kowa Company, Ltd., oral pemafibrate has been approved in Japan for the treatment of hyperlipidaemia (including familial hyperlipidaemia). This article summarizes the milestones in the development of pemafibrate leading to this first global approval for hyperlipidaemia.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Kowa Co. PARMODIA® tab. 0.1 mg: prescribing information. 2017. www.kowa-souyaku.co.jp. Accessed 16 Aug 2017.
Takei K, Han SI, Murayama Y, et al. Selective peroxisome proliferator-activated receptor-alpha modulator K-877 efficiently activates the peroxisome proliferator-activated receptor-alpha pathway and improves lipid metabolism in mice. J Diabetes Investig. 2017;8(4):446–52.
Kowa Co Ltd. [The treatment of hyperlipidemia “Parmodia® tablets 0.1 mg” about acquiring manufacturing and marketing approval in Japan. First time high active and highly selective PPARα modulator in the world]. 2017. http://www.kowa.co.jp. Accessed 16 Aug 2017.
Raza-Iqbal S, Tanaka T, Anai M, et al. Transcriptome analysis of K-877 (a novel selective PPARα modulator (SPPARMα))-regulated genes in primary human hepatocytes and the mouse liver. J Atheroscler Thromb. 2015;22(8):754–72.
Takei K, Nakagawa Y, Wang Y, et al. Effects of K-877, a novel selective PPARα modulator, on small intestine contribute to the amelioration of hyperlipidemia in low-density lipoprotein receptor knockout mice. J Pharmacol Sci. 2017;133(4):214–22.
Hennuyer N, Duplan I, Paquet C, et al. The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis. 2016;249:200–8.
Sairyo M, Kobayashi T, Masuda D, et al. A novel selective PPARα modulator (SPPARMα), K-877 (pemafibrate), attenuates postprandial hypertriglyceridemia in mice. J Atheroscler Thromb. 2017. doi:10.5551/jat.39693.
Yamashita S, Ishibashi S, Arai H, et al. Effect of K-877, a potent and selective PPAR alpha modulator (SPPARM alpha), on postprandial hyperlipidemia in dyslipidemic patients: a randomized cross-over study [abstract no. P5891]. Eur Heart J. 2016;37(Suppl 1):1204.
Yamashita S, Ishibashi S, Arai H, et al. Effect of K-877, a potent and selective PPAR alpha modulator (SPPARM alpha), on cholesterol efflux from macrophages in dyslipidemic patients [abstract no. P5982]. Eur Heart J. 2015;36(Suppl. 1):1047–8.
Araki E, Yamashita S, Arai H, et al. Effects of K-877, a novel selective PPARα modulator (SPPARMα), on lipid and glucose metabolism in fasting and postprandial states in type 2 diabetic patients with dyslipidaemia [abstract no. 1112]. Diabetologia. 2016;59(Suppl. 1):S531.
Ishibashi S, Yamashita S, Arai H, et al. Efficacy and safety of K-877, a potent and selective PPAR-α agonist, in Japanese patients with dyslipidemia [abstract no. 10718]. Circulation. 2013;128(22 Suppl. 1).
Yamashita S, Ishibashi S, Arai H, et al. Comparison of the novel peroxisome proliferator-activated receptor alpha agonist K-877 and fenofibrate on high-density lipoprotein subclass distribution determined by high-performance liquid chromatography in patients with dyslipidemia [abstract no. 15652]. Circulation. 2013;128(22 Suppl. 1).
Arai H, Yamashita S, Yokote K, et al. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis. 2017;261:144–52.
Kastelein JJP, Senko Y, Hounslow N, et al. K-877, a selective PPAR alpha modulator (SPPARM alpha), ameliorates dyslipidaemia in patients with well-controlled LDL cholesterol levels on statin therapy, without increases in serum creatinine [abstract no. P5983]. Eur Heart J. 2015;36(Suppl. 1):1048.
Kastelein JJP, Senko Y, Hounslow N, et al. K-877, a selective PPAR alpha modulator (SPPARM alpha), improves dyslipidaemia in statin-treated patients with type 2 diabetes mellitus [abstract no. P5985]. Eur Heart J. 2015;36(Suppl. 1):1048.
Ishibashi S, Yamashita S, Arai H, et al. Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: a randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis. 2016;249:36–43.
The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. H. A. Blair is a salaried employee of Adis, Springer SBM.
Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/B8FBF0603C57D013.
This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through preclinical and clinical studies to market launch and beyond.
About this article
Cite this article
Blair, H.A. Pemafibrate: First Global Approval. Drugs 77, 1805–1810 (2017). https://doi.org/10.1007/s40265-017-0818-x