Last updated on April 21, 2014 at 1:20 EDT

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

May 20, 2011

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,

Study Details

A total of 5 LPLD patients were administered Glybera (1×1012 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

Source: newswire