Date: 2017-12-21
Type of
information: Initiation of development program
phase: 2a
Announcement: initiation of development program
Company: Gemphire Therapeutics (USA - Mich)
Product: gemcabene
Action
mechanism:
- Gemcabene is a lipid-lowering small molecule. Its mechanism of action is designed to enhance the clearance of very low-density lipoproteins (VLDLs) in the plasma and inhibition of the production of cholesterol and triglycerides in the liver. The combined effect of these mechanisms has been clinically observed to result in a reduction of plasma non-HDL-C, VLDL-C, LDL-C, apolipoprotein B and triglycerides. In addition, gemcabene has been shown to markedly lower C-reactive protein in humans and improve insulin sensitization.
- Gemcabene’s MOA is liver-directed involving downregulation of hepatic apolipoprotein C-III (apoC-III) mRNA expression and decrease of plasma apoC-III levels. Gemcabene has also been shown to reduce liver sulfatase-2 mRNA levels, known to be elevated in diabetic and obese patients. Elevated sulfatase-2 is thought to reduce the effectiveness of the liver VLDL-remnant receptor (also known as Syndecan-1), that normally plays a role in removing triglyceride containing particles from the plasma. Gemcabene also reduces acetyl-CoA carboxylase (ACC1) and CCR2/CCR5 receptor mRNA levels, markers involved in the progression of NASH/NAFLD.
Disease: NASH (non-alcoholic steatohepatitis)/nonalcoholic fatty liver disease (NAFLD) - Familial Partial Lipodystrophy (FPL)
Therapeutic
area: Liver diseases - Hepatic diseases
Country: USA
Trial
details:
- The primary objective of this phase 2a study is to assess the efficacy and safety of two dosing regimens of gemcabene in up to eight Familial Partial Lipodystrophy (FPL) patients with elevated triglycerides (TG) and NAFLD. At entry, patients must have a fasting TG value ? 250 mg/dL and quantifiable steatosis (stage 2 or 3) while on a stable, low-fat, low-cholesterol diet. Patients will be randomized to two treatment groups, to receive either gemcabene 300 mg once daily for 24 weeks or gemcabene 300 mg once daily for 12 weeks immediately followed by gemcabene 600 mg once daily for a further 12 weeks.
- The trial’s primary endpoint is the reduction in TG after 12 weeks of treatment. Secondary endpoints will include measures of liver fat (MRI-PDFF) and NAS (histology) at 24 weeks. Patients who are considered responders (i.e., defined as TG lowering > 30% at Week 12) will be offered the opportunity for long-term therapy with gemcabene in a separate open-label extension study.
Latest
news:
- • On December 21, 2017, Gemphire Therapeutics announced the launch of a clinical program to develop gemcabene as a treatment for NASH/nonalcoholic fatty liver disease (NAFLD). The company has an open Investigational New Drug (IND) application for gemcabene in NASH. The program is beginning with a Phase 2a proof-of-concept (POC) clinical trial in adults with FPL, a rare genetic disorder and orphan disease characterized by an abnormal distribution of fatty (adipose) tissue, which can lead to a variety of metabolic abnormalities including NASH. Gemphire anticipates top line results from the trial in the second half of 2018. In addition, The company also plans to launch a second Phase 2a POC trial in NASH early in 2018.
- • On January 9, 2017, Gemphire Therapeutics announced expanded utility for gemcabene with preclinical data results demonstrating proof of concept efficacy in an animal model of nonalcoholic steatohepatitis. The study investigated the effects of gemcabene on the widely used STAM™ mouse model of NASH/fibrosis. In this model, diabetic mice that are fed a high fat diet rapidly develop fatty liver disease. When the mice were administered gemcabene, a hepatoprotective effect preventing liver disease progression was observed, in contrast to the control group. Specifically, gemcabene treatment resulted in a significant lowering of the liver NAFLD activity score (NAS), a composite measure of fatty liver disease comprised of measures of steatosis, inflammation, and hepatocyte ballooning. Progression of liver fibrosis was also significantly reduced with gemcabene treatment. Additionally, hepatic gene expression and plasma markers indicative of inflammation (e.g., CRP and CCR2/CCR5), and lipid modulation (e.g., ApoC-III) were significantly reduced as were other markers. The complete NASH preclinical results will be submitted for publication in 2017.
- Gemphire plans to initiate clinical development of gemcabene in NASH/nonalcoholic fatty liver disease (NAFLD) with a Phase 2 trial (AZURE-1) in 2017.
Is
general: Yes
