Antisense Agent Promising in Rare Triglyceride Disorder

Larry Hand

March 06, 2017

CARLSBAD, CA and CAMBRIDGE, MA — In the 52-week phase 3 APPROACH study involving 66 patients, volanesorsen met its primary end point of significant reduction in triglycerides in patients with familial chylomicronemia syndrome (FCS), in early top-line results announced by Akcea Therapeutics[1].

Volanesorsen is an antisense drug designed to reduce triglyceride levels by reducing production of the liver protein apolipoprotein C-III. Akcea is a wholly owned subsidiary of Ionis Pharmaceuticals.

FCS, characterized by extremely high triglyceride levels, affects 3000 to 5000 people worldwide, the company notes. No effective therapy currently exists. The average triglyceride level of  those in the study was 2209 mg/dL.

For this study, 33 patients treated with volanesorsen experienced mean reductions of 77% from baseline after 3 months of treatment (P<0.0001), with a mean absolute reduction of 1712 mg/dL. That compares with a mean increase of 18% in patients receiving placebo.

The treatment effect persisted over a 52-week treatment period.

About half the volanesorsen-treated patients who had triglyceride levels of ≥750 mg/dL had triglyceride levels <500 mg/dL after 3 months of treatment (P<0.003), while none of the placebo patients experienced the same level of decrease.

Treated patients with high frequencies of pancreatitis attacks upon entering the study experienced no such attacks during 52 weeks of treatment (P<0.02).

Treated patients, compared with placebo patients, experienced reductions in abdominal pain.

No treatment-related liver adverse events and no increases in liver fat occurred during the study, and no treatment-related renal adverse events occurred.

Injection-site reactions turned out to be the most common adverse event in treated patients, with five patients discontinuing due to that.

Many treated patients experienced declines in platelet counts, with five treated patients discontinuing for that reason. After researchers implemented platelet monitoring, no treated patients discontinued due to declines in platelet counts.

Akcea said it will use the APPROACH study data to support the regulatory submission for volanesorsen for FCS.

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