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

Nature Reviews Drug Discovery volume 12, page 719 (2013)Cite this article

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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)1. 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 pancreatitis2, 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)3, and a previous recommendation of the EMA's Committee for Advanced Therapies (CAT)4,5.

The approval process for Glybera was extensively discussed in the scientific community, sometimes critically6,7,8,9,10,11,12. 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 positive5, whereas the CHMP maintained its negative opinion13. 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.

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Figure 1: Authorized orphan drugs and ultra-orphan conditions.

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Acknowledgements

The authors thank J. Llinares, Head of Orphan Medicines at the European Medicines Agency (EMA), for providing figures on authorized orphan drugs. The authors also thank G. Rasi, Executive Director of the EMA, and H.-G. Eichler, Senior Medical Officer of the EMA, for their continuous support.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, the University of Rome “Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy; member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Daniela Melchiorri

  2. member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Daniela Melchiorri

  3. Italian Medicines Agency (Agenzia Italiana del Farmaco), Via del Tritone, 181, 00187 Rome, Italy; member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Luca Pani

  4. member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Luca Pani

  5. University of Trieste (Medical Genetics), Via dell'Istria 65, 34100, Trieste, Italy; member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Paolo Gasparini

  6. member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Paolo Gasparini

  7. Department of Cell and Development Biology, University College London, 21, University Street, London WC1E 6BT, UK; member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Giulio Cossu

  8. member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Giulio Cossu

  9. University of Latvia (Faculty of Biology), Kronvalda Blvd. 4, LV-1586 Riga, Latvia; member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Janis Ancans

  10. member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Janis Ancans

  11. Medicines Authority of Malta, 203, Level 3, rue D'Argens, Gzira 1368, Malta; member of the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    John Joseph Borg

  12. member of the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    John Joseph Borg

  13. European Medicines Agency (EMA), 7 Westferry Circus, London, E14 4HB, Canary Wharf, UK

    Catherine Drai

  14. The Warsaw Medical University (Department of General and Transplantation Surgery), Nowogrodka 59, 02-006 Warsaw, Poland; the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, ul. Zabkowska 41, 03-736 Warsaw, Poland Warsaw, Poland; member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Piotr Fiedor

  15. the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, ul. Zabkowska 41, 03-736 Warsaw, Poland Warsaw, Poland,

    Piotr Fiedor

  16. Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany; member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Egbert Flory

  17. member of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Egbert Flory

  18. Medicines and Healthcare products Regulatory Agency (MHRA), 151 Buckingham Palace Road, Victoria, London SW1W 9SZ, UK; Vice-Chair of the Committee for Medicinal Products for Human Use (CHMP) the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Ian Hudson

  19. Vice-Chair of the Committee for Medicinal Products for Human Use (CHMP) the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Ian Hudson

  20. Medicines Evaluation Board (CBG-MEB), Graadt van Roggenweg 500, 3531 AH Utrecht, The Netherlands; Utrecht Institute for Pharmaceutical Sciences (UIPS), PO Box 80 082, 3508 TB Utrecht, The Netherlands; member of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Hubert G. Leufkens

  21. Utrecht Institute for Pharmaceutical Sciences (UIPS), PO Box 80 082, 3508 TB Utrecht, The Netherlands,

    Hubert G. Leufkens

  22. Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, D-63225 Langen, Germany; member of the Committee for Medicinal Products for Human Use (CHMP) and the Scientific Advice Working Party (SAWP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Jan Müller-Berghaus

  23. member of the Committee for Medicinal Products for Human Use (CHMP) and the Scientific Advice Working Party (SAWP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Jan Müller-Berghaus

  24. Medicines and Healthcare products Regulatory Agency (MHRA), 151 Buckingham Palace Road, Victoria, London SW1W 9SZ, UK; member of the Committee for Advanced Therapies (CAT) and the Scientific Advice Working Party (SAWP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Gopalan Narayanan

  25. member of the Committee for Advanced Therapies (CAT) and the Scientific Advice Working Party (SAWP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Gopalan Narayanan

  26. European Medicines Agency (EMA), 7 Westferry Circus, London, E14 4HB, Canary Wharf, UK

    Brigitte Neugebauer

  27. Medical Faculty, Riga Stradinš University, 16 Dzirciema Street, Riga LV-1007, Latvia; member of the Committee for Medicinal Products for Human Use (CHMP) the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Juris Pokrotnieks

  28. member of the Committee for Medicinal Products for Human Use (CHMP) the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Juris Pokrotnieks

  29. Laboratoire National de Santé, Service du Contrôle des Médicaments, 1A rue A Lumière, 1011 Luxembourg, Luxembourg; Chair of Quality Working Party (QWP), member of the Committee for Advanced Therapies (CAT) and of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Jean-Louis Robert

  30. Chair of Quality Working Party (QWP), member of the Committee for Advanced Therapies (CAT) and of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Jean-Louis Robert

  31. Medical Products Agency, Dag Hammarskjölds väg 42, 75103 Uppsala, Sweden; Chair of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Tomas Salmonson

  32. Chair of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Tomas Salmonson

  33. Danish Health and Medicines Authority, Axel Heides Gade 1, DK-2300 Copenhagen, Denmark; Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany; Chair of the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), 7 Westferry Circus, Canary Wharf, London E14 4HB, UK.,

    Christian K. Schneider

  34. Twincore Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany,

    Christian K. Schneider

Authors
  1. Daniela Melchiorri
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  2. Luca Pani
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  6. John Joseph Borg
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  10. Ian Hudson
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  16. Jean-Louis Robert
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  17. Tomas Salmonson
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  18. Christian K. Schneider
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Corresponding author

Correspondence to Christian K. Schneider.

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The authors declare no competing financial interests.

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Melchiorri, D., Pani, L., Gasparini, P. et al. Regulatory evaluation of Glybera in Europe — two committees, one mission. Nat Rev Drug Discov 12, 719 (2013). https://doi.org/10.1038/nrd3835-c1

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