Study to Re-assess and Re-confirm Data Previously Recorded About the Incidence and Severity of Acute Abdominal "Pancreatitis" Episodes in Lipoprotein Lipase Deficient (LPLD) Subjects Previously Enrolled on AMT Clinical Studies

Lipoprotein lipase deficiency (LPLD) is an autosomal recessive inherited condition caused by homozygosity or compound heterozygosity for mutations within the LPL gene.

The most severe clinical complication associated with LPLD is acute pancreatitis. Pancreatitis in an LPLD subject often leads to prolonged hospital admissions. Subjects who survive repeated episodes of acute pancreatitis may develop chronic pancreatitis, ultimately resulting in endocrine and exocrine pancreatic insufficiency.

The clinical manifestations of acute pancreatitis episodes related to LPLD are largely indistinguishable from acute pancreatitis due to other causes. However, collection of data relating to hospital admissions, laboratory test results, scan images and adverse events occurring concomitantly to the acute pancreatic episode should allow elimination of other causes of pancreatitis (e.g. gallstones etc) and ultimately allow confirmation of LPLD-related acute pancreatitis. Characterisation of the presentation of symptoms which occur around the time of known episodes of LPLD-related acute pancreatitis should also permit identification of episodes of acute pancreatitis which have previously been considered as unrelated or even unrecognized.

Alipogene tiparvovec (Glybera®) is in development for the therapy of LPLD. In summary, alipogene tiparvovec contains the human lipoprotein (LPL) gene variant LPLS447X in a non-replicating vector in solution administered in a one-time series of intramuscular injections in the arms/legs.

Studies conducted to date with Glybera have evaluated total triglyceride levels as a surrogate marker for efficacy and have not evaluated a clinical endpoint such as acute pancreatitis episodes as a primary endpoint. Post-hoc analysis has suggested that there may be a reduction in the frequency of acute abdominal pancreatitis episodes reported following treatment compared to the frequency reported pre-treatment from past medical history records. The recorded episodes used in this post-hoc analysis were collected from medical history and adverse event data but no uniform criteria were used to classify these as episodes of acute pancreatitis. Review of the post hoc analysis has raised questions that the recorded past medical history of pancreatitis episodes may be inaccurate with respect to diagnosis and number of episodes.

In this case record review study, data will be collected on pancreatitis episodes from subjects who previously enrolled in studies PREPARATION-02 (observational), CT-AMT-011-01 and CT-AMT-011-02. In studies CT-AMT-011-01 and CT-AMT-011-02 subjects received AMT-011 at either dose 3 x 1011 gc/kg or 1 x 1012 gc/kg. Data obtained from medical records, hospital admission/discharge charts, laboratory results and imaging scans will be evaluated for evidence of LPLD-related episodes of pancreatitis by an expert review panel. The evaluation will consider data collected from three time periods:

• subjects entire past medical history,
• the period after enrolment into study but prior to AMT-011 therapy,
• the period post-administration of AMT-011.

Data from the subjects who did not progress to receive AMT-011 will be evaluated as a control group using data collected from past medical history and from the period after enrolment in the PREPARATION-02.