An open label, long term, safety and tolerability extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with Familial Chylomicronemia Syndrome

Familial Chylomicronemia Syndrome (FCS) is a rare genetic disease due to loss
of capacity to hydrolyze triglycerides (TG) circulating in TG-rich lipoproteins
(primarily chylomicrons) resulting in severe hypertriglyceridemia (>8.4 mmol/L)
in both the post-prandial and fasting state. The most severe consequence of FCS
is acute pancreatitis, which can be severe and life-threatening LCQ908 is a
potent and selective DGAT1 inhibitor. DGAT catalyzes the final step in TG
synthesis. LCQ908 may reduce plasma TG levels and chylomicrom synthesis in
patients with FCS and may therefore have a beneficial effect on the
pathophysiology of chylomicronemia.

The purpose of this study is to determine long-term safety and tolerability,
and continued efficacy in lowering triglycerides of LCQ908 in subjects FCS.

This is a multicentre open-label trial consisting of 2 parts:
Part A:
Week 1 to 8: Patients will receive LCQ908 10mg/day
Week 9 to 16: LCQ 10 mg/ day may be possibly uptitrated with 10 mg. Durring
this period patients may receive 10 mg/day or 20 mg/day LCQ908 Week 16 to 52:
LCQ intake may possibly be uptitrated with 10 mg or 20 mg LCQ. During this
period patients may receive 10 mg/day, 20 mg/day LCQ908 or 40 mg/dag LCQ908.
Part B:
week 52 to week 130: patients continue the study medication dose from part A

Intervention consists of LCQ908 10 mg, LCQ908 20 mg or LCQ908 40 mg

This study will last for 130 weeks. During each visit a fasting blood sample
will be taken and vital signs will be assessed. The EQ-5D questionnaire will be
assessed during 4 visits, ECG measurements will be assessed during 3 visits and
physical exams will be performed during 3 visits.

LCQ908 has been given to humans in single doses up to 300 mg and in multiple
doses up to 20 mg for 12 weeks. All dose levels have been found to be safe.
Over 1000 humans have been treated, including approximately 400 healthy
volunteers, 600 patients with Type 2 diabetes, and 6 patients with FCS. In
general, a dose-dependent occurrence of watery diarrhea was found that was
generally mild. Adverse events also included nausea and abdominal discomfort.
Draft preliminary results of the study with 6 FCS patients indicate that LCQ908
use for 21 days was safe and well tolerated at 10, 20 & 40 mg, with no
clinically significant laboratory abnormalities or clinical findings attributed
to LCQ908. There were some mild gastrointestinal adverse events recorded, but
the frequency and duration was less than in healthy volunteer studies. There is
a risk of hypersensitivity to sunlight at LCQ908 intake, although this has not
been observed in humans.