Triglycerides Fall in Phase 3 Trial of Novel Antisense Inhibitor

Larry Hand

December 19, 2016

CAMBRIDGE, MA — Akcea Therapeutics today announced that its phase 3 COMPASS clinical trial for volanesorsen met its primary end point of significant mean reduction in triglycerides in patients with severe hypertriglyceridemia[1].

Volanesorsen is an antisense drug designed to reduce triglyceride levels by targeting apolipoprotein C-III. Akcea, a wholly owned subsidiary of Ionis Pharmaceuticals (Carlsbad, CA), is developing the drug to treat patients with the rare metabolic disorders FCS and familial partial lipodystrophy.

Akcea said in a statement that treatment with volanesorsen in 75 patients resulted in a mean reduction of 71.2% from baseline after 13 weeks of treatment (P<0.0001). That represents an absolute reduction of 869 mg/dL in patients who entered the study with an average triglyceride level of 1261 mg/dL.

That compares with a reduction of 0.9% in 38 patients who received placebo.

The company also said that, in a subset of five patients with familial chylomicronemia syndrome (FCS), volanesorsen-treated patients experienced a mean reduction in triglycerides of 73% from baseline after 13 weeks of treatment. That represents an absolute reduction of 1511 mg/dL for patients who entered the study with an average triglyceride level of 2280 mg/dL.

That compares with a mean increase of 70% for two patients treated with placebo.

The treatment effect was sustained in both instances throughout the 24-week trial.

Most volanesorsen-treated patients (82%) experienced triglyceride levels less than 500 mg/dL after 13 weeks, compared with 14% of placebo-treated patients (P<0.0001).

Injection-site reactions were the most common adverse event in volanesorsen-treated patients, with 13% of treated patients discontinuing the study due to this. While 7% of patients discontinued due to other nonserious events, no patients died during the study. No serious platelet events occurred.

COMPASS is one of four global trials in the phase 3 volanesorsen program. The company plans to have data from the other trials in 2017 and 2019.

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  1. Ionis Pharmaceuticals. Akcea and Ionis announce positive results from COMPASS phase 3 study of volanesorsen [press release]. December 19, 2016. Available here.