Amsterdam Molecular Therapeutics (AMT) a leader in the field of human gene therapy, announced that it has received an opinion on its Marketing Authorisation Application (MAA) for Glybera (alipogene tiparvovec) as a potential therapy for Lipoprotein Lipase Deficiency (LPLD). Following a recent meeting with the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP), AMT has been notified that, at this time, Glybera is not approvable.

Subsequent to a review of the CHMP's letter, AMT believes that Glybera can receive a positive opinion subject to generating additional data from existing patients. AMT has therefore decided to ask for a re-examination of the clinical data package.

“From what we know today, despite the disappointment, we believe that there is an indication from the CHMP that Glybera could receive approval and that the current opinion at this time is a reflection of insufficient proof of clinical benefit of Glybera as a result of low patient numbers measured for chylomicron handling for at least 12 months post treatment. The CHMP also indicated that if certain additional data from already treated patients would confirm current results by the end of 2011, an approval may be possible,” noted Jörn Aldag, CEO of AMT. “In the dossier, we provided important data showing Glybera is safe and prevents episodes of pancreatitis, the major clinical complication of LPLD. We appreciate the CHMP's responsibility for caution on such an advanced therapy, so we will work diligently to generate more information and, we hope, ensure that Glybera will still reach patients.”

As part of the MAA, AMT presented data to the CHMP on Glybera showing evidence in reducing the risk of pancreatitis. Also, the company demonstrated a clear signal of patients' ability to break down large chylomicron molecules, the accumulation of which, after intake of dietary fat, seems to be responsible for the occurrence of pancreatitis in LPLD patients. AMT is initiating study CT-AMT-011-04 to examine further how already treated patients handle chylomicrons over time. In addition, AMT will continue to collect follow up data on pancreatitis incidence. AMT's available funds will support its existing operations beyond the completion of the re-examination process into 2012.

“Based on communication from EMA, we understand that our technology platform using Adeno-Associated Virus (AAV) vectors is approvable,” Aldag added. “While we pursue the re-examination of Glybera, we will also continue development of other products in our pipeline such as haemophilia B and GDNF gene therapy for Parkinson's disease and Huntington's disease. We will also continue our preparations for registrations in Canada and the US.”

AMT has developed Glybera as a treatment for patients with the genetic disorder lipoprotein lipase deficiency. LPLD is an orphan disease for which no treatment exists today. The disease is caused by mutations in the LPL gene, resulting in highly decreased or absent activity of LPL protein in patients. This protein is needed in order to break down large fat-carrying particles that circulate in the blood after each meal. When such particles, called chylomicrons, accumulate in the blood, they may obstruct small blood vessels. Excess chylomicrons result in recurrent and severe acute inflammation of the pancreas, called pancreatitis, the most debilitating complication of LPLD. Glybera has orphan drug status in the EU and US.

AMT is a world leader in the development of human gene based therapies. In addition to Glybera, AMT has a product pipeline of several gene therapy products in development for haemophilia B, Duchenne muscular dystrophy, acute intermittent porphyria, Parkinson's disease and SanfilippoB.