Antisense Inhibitors of ApoC3 and Lp(a) Show Positive Results in Phase 1 and 2 Studies

Topic: Dyslipidemia date: 08/05/2015 Featured Expert: N/A

Two new, investigational antisense inhibitors of ApoC3 and Lp(a) showed positive results in separate trials of patients with elevated triglycerides and Lp(a).


In a Phase 2 trial, patients with very high to severely high triglycerides who were treated with the investigational drug, volanesorsen (Akcea Therapeutics), a second-generation antisense inhibitor of apolipoprotein C-III (ApoC3) synthesis, achieved mean reductions of up to 80% in ApoC3 and up to 71% in triglycerides. HDL-C levels increased, on average, up to 46%. The trial was double-blinded, randomized, placebo-controlled, and conducted over 13 weeks to assess the safety and activity of volanesorsen as monotherapy and as an add-on to fibrates. Phase 3 study (APPROACH) is ongoing in patients with familial chylomicronemia syndrome (FCS) and another Phase 3 study is planned for later this year in patients with familial partial lipodystrophy (FPL).

In a separate, Phase 1 study that was also double-blinded, randomized, and placebo-controlled, healthy volunteers who had elevated lipoprotein(a) concentrations of 25 nmol/L or more were given single and multiple ascending doses of the investigational ISIS-APO(a)Rx, an antisense drug targeted at reducing Lp(a), over a 4-week period. Patients given ISIS-APO(a)Rx showed reductions of plasma Lp(a) up to 89% and up to 90% reduction in Lp(a) associated oxidized phospholipids at 30 days, which play an important role in proinflammatory and proatherogenic processes. Phase 2 study is ongoing.

For the latest updates, attend the popular CMHC session, “Late-Breaking Clinical Trials and FDA Update” on Thursday, October 22, 2015.

References: Gaudet D, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373:438-447.

Tsimikas S, et al. Antisense therapy targeting apolipoprotein (a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet. 2015 Jul 22. pii: S0140-6736(15)61252-1.

BACK