PHILADELPHIA — Confirming results previously announced, patients with hypertriglyceridemia treated with volanesorsen experienced a decrease in their triglyceride levels, according to a late-breaking abstract presentation at National Lipid Association Scientific Sessions.
“We don’t have enough drugs to adequately decrease triglyceride levels in many patients with severe hypertriglyceridemia, and what the COMPASS study showed is that we may have now a new therapeutic option to decrease triglycerides massively by approximately 70% in such patients,” Ioanna Gouni-Berthold, MD, professor of medicine and senior registrar at the Polyclinic for Endocrinology, Diabetes and Preventive Medicine at the University of Cologne in Germany and an investigator in the study, said in an interview with Cardiology Today.
The COMPASS study was a supportive study used to further validate findings from a randomized, double blind, placebo-controlled, phase 3 study of volanesorsen in the treatment of familial chylomicronemia syndrome, known as the APPROACH study. In the COMPASS trial, researchers assessed the effects of volanesorsen on triglyceride concentrations through the analysis of data from 113 patients with fasting triglyceride levels ≥ 500 mg/dL.
“I find the mechanism of action of this drug very interesting,” Gouni-Berthold told Cardiology Today. “It blocks the synthesis of ApoC-III, and ApoC-III is a protein that may be associated with [CVD]. In one single issue of The New England Journal [of Medicine] in July 2014, there were two independent publications showing that loss-of-function mutations in APOC3 are associated with reduced risk of [CVD]. Therefore, it would be interesting to have a drug that both robustly decreases triglycerides and may also decrease the risk of CVD by inhibiting ApoC-III synthesis.”
In the COMPASS study, patients were assigned to either receive 300 mg of volanesorsen subcutaneously once a week (n = 75) or placebo (n = 38) for 26 weeks.
At 3 months, triglyceride levels in patients in the volanesorsen group were reduced by a mean of 71% from baseline vs. 1% in patients in the placebo group (P < .0001). Treated patients achieved a mean absolute reduction of 869 mg/dL.
Patients assigned volanesorsen with familial chylomicronemia syndrome (n = 5) with average baseline triglyceride levels of 2,280 ± 973 mg/dL experienced a decrease in triglycerides of 73%. Treatment effects were seen in all groups throughout 26 weeks.
Volanesorsen also significantly reduced pancreatitis events (P = .036). No events occurred in the volanesorsen group during the study period vs. five events in the placebo group.
“Until now, we just have statins, fibrates, nicotinic acid and omega-3 fatty acids to lower triglyceride levels, and very often, even if I have my patients on all of them, they still are above the threshold for pancreatitis,” Gouni-Berthold told Cardiology Today.
“If [volanesorsen] would be approved for the treatment of hypertriglyceridemia, and assuming the till now acceptable safety profile, it could help clinicians to finally have a drug that robustly decreases triglyceride levels and may also decrease the incidence of pancreatitis,” Gouni-Berthold said. – by Darlene Dobkowski
Gouni-Berthold I, et al. Abstract 135. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.
Disclosure: The study was funded by Akcea Therapeutics/Ionis Pharmaceuticals. Gouni-Berthold reports receiving support from Akcea Therapeutics/Ionis Pharmaceuticals to present the data at the NLA Scientific Sessions.
Editor’s Note: This article was updated on June 1, 2017 to reflect updates to the data.