Regulatory evaluation of Glybera in Europe-two committees, one mission

Representing the first gene therapy to be approved in the Western world, alipogene tiparvovec (Glybera; Uniqure) has recently been said to have had a “substantial impact from a regulatory perspective” (Nature Rev. Drug Discov. 11, 664; 2012). The therapy was granted marketing authorization in the European Union for the treatment of lipoprotein lipase deficiency, which results in a clinically heterogeneous condition with a risk of potentially life-threatening pancreatitis, at the end of 2012. The decision followed a positive opinion by the European Medicines Agency (EMA)'s Committee for Medicinal Products for Human Use (CHMP), and a previous recommendation of the EMA's Committee for Advanced Therapies (CAT). The approval process for Glybera was extensively discussed in the scientific community, sometimes critically. During the process, the opinions of the CHMP and the CAT differed: although the opinion of both committees was originally negative, in a “re-examination procedure” the opinion of the CAT became positive, whereas the CHMP maintained its negative opinion. However, both committees finally recommended approval of the medicine. As regulators who have been involved in this approval process, we would like to provide insight into why the Glybera procedure was challenging, and give assurance to the scientific community regarding confidence in both orphan drug and gene therapy regulation in Europe.