Gemphire Completes Patient Enrollment in INDIGO-1 Trial in Severe Hypertriglyceridemia (SHTG) Patients
On Track to Report Top-Line Data from Phase 2b Trial in Second Quarter of 2018
“The INDIGO-1 trial is part of a comprehensive clinical program to develop gemcabene for a broad spectrum of dyslipidemia conditions,” said Dr.
INDIGO-1 is a 12 week, multicenter, double-blind, placebo-controlled, randomized trial in patients with SHTG (TG ≥ 500mg/dL) with or without background statin therapy. Patients are enrolled into one of three arms: gemcabene 300 mg, gemcabene 600 mg or placebo once daily. The primary endpoint is triglyceride (TG) reduction from baseline after 12 weeks. Other endpoints include LDL‑C, hsCRP, apoB, non-HDL‑C, VLDL-C and total cholesterol. Safety is being assessed by adverse event monitoring, clinical laboratory assessments, ECGs, physical examinations and vital sign assessments. Additional information on the INDIGO-1 trial, including inclusion/exclusion criteria, can be found at www.clinicaltrials.gov, with the NCT Identifier #02944383.
Pursuing SHTG may enable gemcabene to reach a large population of patients with TG levels above 500 mg/dL and offer a convenient, oral, once‑daily dosing with no food effects that may have the potential to result in better efficacy than standard of care, while being well‑tolerated with statins. Based on a 1.1% prevalence rate of TG ≥ 500mg/dL in
“Given gemcabene’s record of safety in over 950 human subjects to date, including its demonstrated ability to provide therapeutic benefits as add-on therapy to maximally-tolerated statins, we believe that it has the potential to become a foundational therapy for SHTG patients,” added Dr.
About Severe Hypertriglyceridemia (SHTG)
SHTG is a condition in which patients have TGs present in the bloodstream at a level of greater than 500 mg/dL. These high TG levels are associated with an increase in the risk for cardiovascular disease and acute pancreatitis. Current first-line treatments for SHTG, as recommended by the ATP III guidelines, include dietary modifications to lower the intake of fatty foods and the use of fibrates, prescription fish oils and/or niacin. Current therapies, limited by insufficient efficacy, drug-drug interaction potential or side-effects, may be inadequate to lower the TG levels below 500 mg/dL, the level at which patients are at risk for increased pancreatitis.
Pancreatitis is an inflammation of the pancreas. Once the gland becomes inflamed, the condition can progress to swelling of the gland and surrounding blood vessels, bleeding, infection, and damage to the gland. Digestive juices become trapped and start digesting the pancreas itself. If the damage persists, the gland may not be able to carry out normal functions. Pancreatitis may be acute (new, short-term) or chronic (ongoing, long-term). Either type can be very severe, and lead to serious complications.
Acute pancreatitis usually begins soon after the damage to the pancreas begins. Attacks are typically very mild. Mild attacks may last for a short time and usually resolve completely as the pancreas returns to normal. Some people only have one attack, whereas other people may have more than one attack. About 20% of cases, however, are very severe. Chronic pancreatitis begins as acute pancreatitis. If the pancreas becomes scarred during the attack of acute pancreatitis, it cannot return to its normal state. The damage to the gland continues, worsening over time. There are reports that more than 300,000 patients are admitted per year for pancreatitis in
High levels of triglycerides are associated with acute pancreatitis and considerable morbidity and mortality. In
Gemcabene’s mechanism of action and safety profile are highly differentiated from other clinical candidates
Gemphire’s product candidate gemcabene is a first-in-class, once-daily, oral therapy that may be suitable for patients who are unable to achieve normal levels of LDL-C or triglycerides with currently approved therapies, primarily statins. Gemcabene's mechanism of action (MOA) 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. Gemcabene has demonstrated POC efficacy for NASH in the rodent STAM™ model developed at SMC Laboratories in Tokyo,
Gemphire is a clinical-stage biopharmaceutical company that is committed to helping patients with cardiometabolic disorders, including dyslipidemia and NASH. The Company is focused on providing new treatment options for cardiometabolic diseases through its complementary, convenient, cost-effective product candidate gemcabene as add-on to the standard of care, especially statins, that will benefit patients, physicians, and payors. Gemphire’s Phase 2 clinical program is evaluating the efficacy and safety of gemcabene in hypercholesterolemia, including FH and ASCVD, SHTG and NASH/NAFLD. Two trials supporting hypercholesterolemia have been completed under NCT02722408 and NCT02634151. Gemphire has completed recruitment for a clinical trial for SHTG under NCT02944383, and has initiated a trial for NASH. Please visit www.gemphire.com for more information.
Forward Looking Statements
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