The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the authorisation of Glybera (alipogene tiparvovec) for marketing in the European Union. It is intended to treat lipoprotein lipase (LPL) deficiency in patients with severe or multiple pancreatitis attacks, despite dietary fat restrictions.
LPL deficiency is an ultra-rare inherited disorder estimated to affect no more than one or two people per million. Due to a defective gene, patients with this disorder cannot produce enough LPL, an enzyme responsible for breaking down fats. So far, management of patients with the disorder consists of strict reduction of dietary fat to less than 20 per cent of the daily caloric intake. It is very difficult to comply with such a dietary regimen and as a consequence many patients experience life-threatening pancreatitis attacks requiring admission to hospital.
Glybera is the first gene therapy medicine to be recommended for authorisation in the European Union. Gene therapy medicines have the potential to cure genetic disorders by replacing a defective gene with a working copy, thus helping the body to recover functionality. Glybera uses an adeno-associated virus vector as the delivery vehicle to add working copies of the LPL gene into muscle cells to enable production of the enzyme in the cells.
The CHMP recommended the granting of the marketing authorisation under ‘exceptional circumstances’. The company that markets Glybera will be required to provide data from a registry set up to monitor outcomes in patients treated with Glybera, which the Agency will review as they become available.
Dr Tomas Salmonson, acting Chair of the CHMP, says, “The evaluation of this application has been a very complex process, but the use of Glybera in a more restricted indication than initially applied for, which targets the patient population with greatest need for treatment, and additional analyses by the Committee for Advanced Therapies (CAT) have added to the robustness of the data provided and allowed the CHMP to conclude that the benefits of Glybera are greater than its known risks. Our established ways of assessing the benefits and risks of Glybera were challenged by the extreme rarity of the condition and also by uncertainties associated with data provided. In close cooperation with the CAT we have worked out a way to ensure robust and close follow-up of the quality, safety and efficacy of Glybera while giving patients who have to live with this rare disease access to a medical treatment.”
The CHMP was advised by the CAT, the Agency’s expert committee for advanced-therapy medicinal products. Both committees have distinct responsibilities in the approval process of advanced-therapy medicines. The CAT adopts a draft opinion, which is taken into account by the CHMP when giving its recommendation regarding the authorisation of a medicine in view of the balance of benefits and risks identified.
“The CAT has worked closely with the CHMP throughout the procedure. I was concerned about reports in the public domain of differences between the two committees during the approval process, since the scientific assessment of the CAT and the CHMP were not far apart. The dossier is maybe a unique case where the ultra-rarity of the disease, its fluctuating rather than continuously progressing clinical course, and the complexity of the scientific data led to difficult scientific decision-making,” said Dr Christian Schneider, the Chair, CAT.
The marketing authorisation application for Glybera was submitted to the Agency in December 2009. In June 2011, both the CHMP and the CAT adopted negative opinions concerning the use of Glybera in the treatment of patients with LPL deficiency. During the re-examination the CAT considered that there was scope for approval of Glybera with additional post-marketing studies, but the CHMP maintained its negative opinion in October 2011.
Following the meeting of the Member States Standing Committee on human medicinal products on 23 January 2012, the European Commission asked the Agency to re-evaluate the application for Glybera in a restricted group of patients with severe or multiple pancreatitis attacks. This was first considered in April 2012. Following detailed scientific discussions in both committees, the CAT adopted a positive draft opinion in June 2012, which has now been endorsed by the CHMP.
The CHMP’s opinion on Glybera will now be sent to the European Commission for the adoption of a marketing authorisation.
EP News Bureau
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