Positive results from Phase III COMPASS study of volanesorsen to treat severe hypertriglyceridemia.- Akcea Therapeutics.

Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals, Inc.has announced that the Phase III COMPASS study met its primary endpoint. COMPASS is a randomized, double-blind, placebo-controlled, 26-week Phase III study evaluating volanesorsen in 113 patients with severe hypertriglyceridemia. The average incoming triglyceride level of patients in the study was 1,261 mg/dl. Patients treated with volanesorsen experienced clinically meaningful benefits on triglycerides as summarized below:- 1.For the primary endpoint of the study, volanesorsen-treated patients (n=75) achieved a statistically significant (p<0.0001) mean reduction in triglycerides of 71.2 from baseline after 13 weeks of treatment compared with a mean reduction of 0.9 in placebo-treated patients n="38)." this represented a mean absolute reduction of 869 mg dl in treated patients. the treatment effect observed was sustained through the end of the 26 week treatment period. - 2.in a subset of seven patients with familial chylomicronemia syndrome fcs whose average incoming triglyceride level was 2280 mg dl volanesorsen-treated patients n="5)" achieved a mean reduction in triglycerides of 73 from baseline after 13 weeks of treatment compared with a mean increase of 70 in placebo-treated patients n="2)." this represented a mean absolute reduction of 1511 mg dl in treated patients. the treatment effect observed was sustained through the end of the 26-week treatment period.- 3.in addition 82 of patients treated with volanesorsen including three of the fcs patients achieved triglyceride levels less than 500 mg dl after 13 weeks of treatment compared to 14 of placebo-treated patients p><0.0001).>

The COMPASS study is an important component of the planned regulatory filings for volanesorsen, an antisense drug designed to decrease triglyceride levels by directly targeting apolipoprotein C-III (ApoC-III), being developed for the treatment of patients with FCS and familial partial lipodystrophy (FPL), two rare metabolic disorders. Ionis and Akcea management plan to discuss the results from this study at an upcoming Ionis pipeline update call on January 5, 2017, and also to present additional data from the study at an upcoming medical meeting.

Comment: This was a Phase III study in patients with severe hypertriglyceridemia, including a subset of patients with familial chylomicronemia syndrome (FCS) in which triglyceride levels are 10-20 times higher than normal, often progressing to pancreatitis. Currently available triglyceride-lowering therapies rarely are beneficial in these patients.