Amsterdam Molecular Therapeutics Presents Data Supporting Role of Chylomicron Clearance as Marker for Glybera(R) Efficacy

AMSTERDAM, May 20, 2011 /PRNewswire-FirstCall/ -- Amsterdam Molecular Therapeutics (Euronext: AMT), a leader in the field of human gene therapy, announced today results from a long-term efficacy study of Glybera (alipogene tiparvovec) that showed improved chylomicron metabolism could be used as a biomarker for increased lipoprotein lipase (LPL) activity in those patients missing the gene that produces this protein. Glybera is a gene therapy product under development for the treatment of lipoprotein lipase deficiency (LPLD) that is currently under review for marketing approval with the European Medicines Agency (EMA).

In patients with mutations in the LPL gene, dietary fat (triglyceride molecules) cannot be broken down and so cause chylomicrons, which carry triglycerides around the body, to accumulate in the blood. This may result in recurrent extremely painful and life-threatening episodes of pancreatitis. Data presented last night at the American Society of Gene and Cell Therapy 14th Annual Meeting in Seattle, USA, showed that breakdown of chylomicrons produced after meals was greatly and significantly improved at both 14 and 52 weeks following one-time Glybera administration.

"Lipoprotein lipase plays a central role in chylomicron metabolism so it follows that evidence of improved long-term clearance following Glybera administration could be taken as a measure of efficacy. It also helps to explain the decrease in pancreatitis episodes, the most debilitating portrayal of LPLD, seen in our clinical trials," explained Dr Harald Petry, Head of Research at AMT.

"These data are important as they support the biological activity of Glybera and provide a plausible mechanism of action as well as a measurable marker of effect. We have submitted this data on chylomicron handling to the EMA as part of our Marketing Authorisation Application. We believe a decision by the EMA will be made by mid-2011 as previously guided," noted Jorn Aldag, CEO of AMT.

Study Details

A total of 5 LPLD patients were administered Glybera (1x1012 genome copies/kg, IM). At weeks 14 and 52 post-administration, patients were given a test meal with a tracer molecule designed to monitor the breakdown of newly formed chylomicrons in the blood. Prior to therapy, all patients exhibited poor post-meal chylomicron handling as measured by amount seen in the plasma over 9 hours following meal ingestion. After treatment with Glybera, the amount of tracer found was greatly reduced and in each case was completely eliminated within 9 hours. The effect was consistent in all patients and sustained as observed at both the 14 and 52 week time points.

About Glybera(R)

AMT has developed Glybera as a therapy for patients with the genetic disorder lipoprotein lipase deficiency. LPLD is an orphan disease for which no drug 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(R) has orphan drug status in EU and USA.

About Amsterdam Molecular Therapeutics

AMT is a world leader in the development of human gene based therapies. The company's lead product Glybera(R), a gene therapy for the treatment of lipoprotein lipase deficiency (LPLD), is currently under review by the European Medicines Agency (EMA). If approved, Glybera will be the first gene therapy product to be marketed in Europe. AMT also has a product pipeline of several gene therapy products in development for hemophilia B, Duchenne muscular dystrophy, acute intermittent porphyria, Parkinson's disease, and SanfillipoB. Using adeno-associated viral (AAV) derived vectors as the delivery vehicle of choice for therapeutic genes, the company has been able to design and validate probably the world's first stable and scalable AAV manufacturing platform. This proprietary platform can be applied to a large number of rare (orphan) diseases caused by one faulty gene and allows AMT to pursue its strategy of focusing on this sector of the industry. AMT was founded in 1998 and is based in Amsterdam. Further information can be found at http://www.amtbiopharma.com.

Certain statements in this press release are "forward-looking statements" including those that refer to management's plans and expectations for future operations, prospects and financial condition. Words such as "strategy," "expects," "plans," "anticipates," "believes," "will," "continues," "estimates," "intends," "projects," "goals," "targets" and other words of similar meaning are intended to identify such forward-looking statements. Such statements are based on the current expectations of the management of AMT only. Undue reliance should not be placed on these statements because, by their nature, they are subject to known and unknown risks and can be affected by factors that are beyond the control of AMT. Actual results could differ materially from current expectations due to a number of factors and uncertainties affecting AMT's business. AMT expressly disclaims any intent or obligation to update any forward-looking statements herein except as required by law.

SOURCE Amsterdam Molecular Therapeutics B.V