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.

Follow Larry Hand on Twitter: @LarryHand16. For more from, follow us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: