1.Re-examination of regulatory opinions in Europe: possible contribution for the approval of the first gene therapy product Glybera.
Watanabe N1, Yano K2, Tsuyuki K3, Okano T4, Yamato M1. Mol Ther Methods Clin Dev. 2015 Feb 11;2:14066. doi: 10.1038/mtm.2014.66. eCollection 2015.
The first commercially approved human gene therapy in the Western world is Glybera (alipogene tiparvovec), which is an adenoassociated viral vector encoding the lipoprotein lipase gene. Glybera was recommended for marketing authorization by the European Medicines Agency in 2012. The European Medicines Agency had only ever reviewed three marketing authorization applications for gene therapy medicinal products. Unlike in the case of Glybera, the applications of the first two products, Cerepro and Contusugene Ladenovec Gendux/Advexin, both of which were for cancer diseases, were withdrawn. In this report, we studied the European public assessment reports of the three gene therapy products. During the assessment process, Glybera was re-examined and reviewed for a fourth time. We therefore researched the re-examination procedure of the European Union regulatory process. Approximately 25% of the new medicinal products initially given negative opinions from the Committee for Medicinal Products for Human Use were ultimately approved after re-examination from 2009 to 2013.
2.Recent advances in pharmacotherapy for hypertriglyceridemia.
Sahebkar A1, Chew GT2, Watts GF3. Prog Lipid Res. 2014 Oct;56:47-66. doi: 10.1016/j.plipres.2014.07.002. Epub 2014 Jul 30.
Elevated plasma triglyceride (TG) concentrations are associated with an increased risk of atherosclerotic cardiovascular disease (CVD), hepatic steatosis and pancreatitis. Existing pharmacotherapies, such as fibrates, n-3 polyunsaturated fatty acids (PUFAs) and niacin, are partially efficacious in correcting elevated plasma TG. However, several new TG-lowering agents are in development that can regulate the transport of triglyceride-rich lipoproteins (TRLs) by modulating key enzymes, receptors or ligands involved in their metabolism. Balanced dual peroxisome proliferator-activated receptor (PPAR) α/γ agonists, inhibitors of microsomal triglyceride transfer protein (MTTP) and acyl-CoA:diacylglycerol acyltransferase-1 (DGAT-1), incretin mimetics, and apolipoprotein (apo) B-targeted antisense oligonucleotides (ASOs) can all decrease the production and secretion of TRLs; inhibitors of cholesteryl ester transfer protein (CETP) and angiopoietin-like proteins (ANGPTLs) 3 and 4, monoclonal antibodies (Mabs) against proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC-III-targeted ASOs, selective peroxisome proliferator-activated receptor modulators (SPPARMs), and lipoprotein lipase (LPL) gene replacement therapy (alipogene tiparvovec) enhance the catabolism and clearance of TRLs; dual PPAR-α/δ agonists and n-3 polyunsaturated fatty acids can lower plasma TG by regulating both TRL secretion and catabolism.
3.Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the European Union.
Narayanan G1, Cossu G, Galli MC, Flory E, Ovelgonne H, Salmikangas P, Schneider CK, Trouvin JH. Hum Gene Ther Clin Dev. 2014 Mar;25(1):1-6. doi: 10.1089/humc.2013.230.
Gene therapy is a rapidly evolving field that needs an integrated approach, as acknowledged in the concept article on the revision of the guideline on gene transfer medicinal products. The first gene therapy application for marketing authorization was approved in the International Conference on Harmonisation (ICH) region in 2012, the product being Alipogene tiparvovec. The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology. Here, as current or previous members of the Committee for Advanced Therapies, we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the European Union to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful marketing authorization.
4.Clinical development of Gene therapy needs a tailored approach: A regulatory perspective from the EU.
Narayanan G1, Salmikangas P, Schneider CK, Galli MC, Trouvin JH, Flory E, Cossu G, Ovelgonne H. Hum Gene Ther Clin Dev. 2014 Feb 18. [Epub ahead of print]
Gene therapy is a rapidly evolving field, which needs an integrated approach, as acknowledged in the Concept paper on the revision of the guideline on gene transfer medicinal products (Concept paper, EMA, 2009). The first gene therapy application for marketing authorisation was approved in the ICH region in 2012, the product being Alipogene tiparvovec (http, summary for the public, 2012). The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology (English, 2011; Flemming, 2012; Melchiorri et al, 2013; Miller, 2012). Here, as current or previous members of the Committee for Advanced Therapies (CAT), we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the EU to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful Marketing Authorisation.