Essentialis' investigational compound DCCR has demonstrated a 30% to 40% reduction in triglyceride (TG) levels in a Phase 2b trial conducted with patients whose TG levels exceeded 500mg/dL.
DCCR is a crystalline salt of diazoxide, available in a controlled-release, once-a-day tablet formulation.
In the Phase 2b double-blind, placebo-controlled study, half of the subjects were included in the atorvastatin combination sub-group and the remaining were in the monotherapy / fenofibrate combination subgroup.
Patients in the atorvastatin combination sub-group received either DCCR 290mg or placebo in combination with atorvastatin 20mg for 18 weeks, while those in the monotherapy / fenofibrate subgroup were randomised to receive either DCCR 290mg or placebo for 12 weeks, followed by co-administration of fenofibrate (Trilipix) 135mg for another six weeks.
DCCR 290mg in combination with statin resulted in placebo-adjusted median reductions of 28% in TG, 51% in very low density lipoprotein-cholesterol (VLDL-C), and 16% in non-high density lipoprotein-cholesterol (non HDL-C) levels with an increase in HDL-C of 11%, the study reported.
In combination with fenofibrate, DCCR showed median reductions in TG of 78%, in non-HDL-C of 34%, and an increase in HDL-C of 38%.
The study also showed that the increase in LDL-C was only 42% in the fenofibrate plus DCCR group when compared to 57% in the fenofibrate plus placebo group.
Following 18 weeks of treatment, DCCR demonstrated nearly a 40% improvement in HOMA-IR, a measure of insulin resistance, and a reduction in median weight of more than 3kg, compared to a worsening of HOMA-IR and no change in median weight in the placebo-treated subjects.
Essentialis president and chief executive officer Aaron D. Berg said: "Our plans to pursue next steps with DCCR are clear - we want to help patients reduce medical risks associated with very high triglyceride levels."
Essentialis board member and scientific advisory board head Richard Pasternak added: "These data clearly motivate us to advance DCCR into larger trials that may demonstrate benefit to patients with multiple disease risk factors."
Image: A crystalline salt of diazoxide has been found to show promise in a Phase 2b trial as monotherapy and in combination with existing lipid therapy. Photo: Benjah-bmm27