Successful Phase III APPROACH study of volanesorsen for treatment of familial chylomicronemia syndrome .- Akcea Therapeutics/Ionis Pharma

Akcea Therapeutics, a wholly owned subsidiary of Ionis Pharmaceuticals, Inc.announced that the pivotal Phase III APPROACH study of volanesorsen met its primary endpoint of reducing triglyceride levels in patients with familial chylomicronemia syndrome (FC).

APPROACH is a randomized, double-blind, placebo-controlled, 52-week Phase III study in 66 patients with FCS, a rare disease affecting approximately 3,000 to 5,000 patients worldwide. The average incoming triglyceride level of patients in the study was 2,209 mg/dL. Patients treated with volanesorsen experienced robust reductions in triglycerides and related benefits as follows: �For the primary endpoint of the study, volanesorsen-treated patients (n=33) achieved a statistically significant (p<0.0001) mean reduction in triglycerides of 77 from baseline after 3 months of treatment compared to a mean increase of 18 in placebo-treated patients n="33)." this represented a mean absolute reduction of 1712 mg dl in treated patients. the treatment effect observed was sustained over the 52-week treatment period. 50 of the treated patients who entered the study with triglycerides 750 mg dl achieved triglyceride levels less than 500 mg dl after 3 months of treatment. by comparison none of the placebo-treated patients achieved this level p><0.003). volanesorsen-treated patients with the highest documented frequency of pancreatitis attacks suffered no attacks during the 52-week treatment period p="0.02)." a reduction in abdominal pain was observed in volanesorsen-treated patients compared to placebo-treated patients.>

The APPROACH study will support the regulatory submission for FCS of volanesorsen. Additional data from the study will be presented at an upcoming medical meeting.The APPROACH results were consistent with findings from both the Phase III COMPASS study as well as the Phase II program for volanesorsen.In the study, there were no treatment-related liver adverse events, including no increases in liver fat. There were no treatment-related renal adverse events. The most common adverse event in the volanesorsen-treated group of patients was injection site reactions (ISRs), which were mostly mild.

Comment: Concerns were expressed at cases of platelet deficiency.Five patients left the study because of falling platelet levels and a further five discontinued due to injection site reactions.A total drop out rate of 30%.Ionis believes with monitoring the issues are manageable.