Date: 2012-03-28
Type of information: Results
phase:
Announcement: results
Company: Amsterdam Molecular Therapeutics (The Netherlands)
Product: Glybera® (alipogene tiparvovec)
Action
mechanism: gene therapy. Glybera® is an adeno-associated viral vector (AAV1) based gene therapy, administered intramuscularly (IM) at multiple-sites in a single session. AAV1 carrying the human variant LPLS447X gene is delivered to skeletal muscle, where it becomes active. The LPL protein is expressed and transported to the capillary endothelium where it binds to chylomicrons and VLDL. Alipogene tiparvovec is intended as a curative measure for patients with LPLD and, as well as enhancing chylomicron metabolism, may prevent episodes of pancreatitis.
Disease: lipoprotein lipase deficiency (LPLD)
[LPLD is a very rare inherited condition that is associated with increased levels of chylomicrons. These particles carry certain types of fat in the blood, which because they are not removed from the body can cause recurrent pancreatitis.]
Therapeutic area: Genetic diseases - Rare diseases
Country: Canada
Trial details:
Latest
news: Amsterdam Molecular Therapeutics has announced data demonstrating that one-time administration of the gene therapy Glybera® (alipogene tiparvovec) is able to markedly improve chylomicron (fat particles in the blood) metabolism following consumption of a low fat meal. This results in a much reduced level of newly-formed chylomicrons in the bloodstream, which are considered to be the cause of the acute and recurring bouts of pancreatitis seen in lipoprotein lipase deficiency (LPLD) subjects.
In an open label clinical trial (CT-AMT-011-02), 5 LPLD subjects in Quebec, Canada, were administered alipogene tiparvovec at a dose of 1 x 1012 genome copies per kg. Two weeks before and 14 weeks after administration, chylomicron metabolism, and plasma palmitate (fatty acid) and
glycerol appearance rates were determined following ingestion of a low fat meal. Following administration of alipogene tiparvovec, the triglyceride (TG) content of the chylomicron fraction and the chylomicron-triglyceride (TG)/total plasma TG ratio were reduced throughout the postprandial period. The postprandial peak chylomicron level and chylomicron AUC were greatly reduced (by 79% and 93%, 6- and 24 hours after the test meal, respectively). There were no significant changes in plasma fatty acid and glycerol appearance rates. Plasma glucose, insulin and C-peptide also did not change. The data was obtained from AMT\'s study in patients treated with Glybera in 2009.
Data were published online in the Journal of Clinical Endocrinology & Metabolism (JCEM, Mar 2012 ; Effect of Alipogene Tiparvovec (AAV1-LPLS447X) on Postprandial Chylomicron Metabolism in Lipoprotein Lipase-Deficient Patients. Carpentier AC, Frisch F, Labbé SM, Gagnon R, de Wal J, Greentree S, Petry H, Twisk J, Brisson D, Gaudet D).
