European Medicines Agency (EMA) turns down a second gene therapy product

The elusive target of registering the first gene therapy product in Europe has moved yet again, with Amsterdam Molecular Therapeutics NV receiving notice from the European Medicines Agency (EMA) that Glybera, a treatment for the inherited disorder lipoprotein lipase deficiency, is not approvable.

The EMA told AMT that it has not provided enough evidence of the long-term efficacy of the product, which is designed to generate a fat-digesting enzyme that patients are not able to produce naturally. Lipoprotein lipase deficiency is an extremely rare condition, and the clinical trial data submitted to EMA for approval included only 27 patients.

While EMA did not have any concerns about the safety of Glybera it said AMT had not demonstrated the product has long-term benefits. The case is reminiscent of Cerepro, a gene therapy for treating brain cancer, developed by Ark Therapeutics plc of London. Cerepro was the first gene therapy product ever to be filed for approval with EMA. Although there were no concerns about the safety of the product, the EMA refused approval in March 2010, on the grounds that there was not enough evidence Cerepro was effective.

AMT believes it can avoid repeating this bit of history, saying Glybera can get approval subject to generating additional data from existing patients. The Amsterdam-based company intends to add in this data and then ask for a re-examination, sometime around the end of 2011.

“From what we know today, despite the disappointment, we believe that there is an indication from that Glybera could receive approval,” said Jörn Aldag, CEO of AMT.

As part of its application for marketing approval AMT presented data on Glybera showing it reduces the risk of pancreatitis. This is the most serious effect of lipoprotein lipase deficiency, caused because the inability to digest fat leads to fat accumulating in the pancreas. AMT will now collect more data to show that there is a long-term reduction in the incidence of pancreatitis in treated patients.

“Based on communication from EMA, we understand that our technology platform using adeno-associated virus vectors is approvable,” Aldag said. “While we pursue the re-examination of Glybera, we will also continue development of other products in our pipeline such as hemophilia B and gene therapy for Parkinson's disease and Huntington's disease. We will also continue our preparations for registrations in Canada and the US.”