|Gemphire to Present New COBALT-1 Clinical Data at the 2017 FH Global Summit|
COBALT-1 results show significant LDL-C lowering for FH patients, including a mean reduction in LDL-C of 39% in the HeFH population
Gemcabene demonstrates novel mechanism to significantly lower LDL-C in FH patients with non-functioning (deficient) LDL receptors
Gemcabene 600 mg demonstrated a median reduction of 33% in inflammatory biomarker hsCRP
Gemcabene demonstrated significant LDL-C lowering on top of PCSK9 inhibitors
COBALT-1 results demonstrate LDL-C lowering benefit for a broad FH population
“The positive COBALT-1 data underscore the benefits that gemcabene can bring to a broad FH population,” said Dr.
“FH is associated with a markedly elevated risk of coronary heart disease, stroke, and peripheral vascular disease. Although a number of lipid-lowering treatments are available, achievement of target LDL-C level remains a challenge for these patients,” said Dr.
COBALT-1 was designed to enroll patients clinically or genetically diagnosed with HoFH, who were on a variety of background lipid lowering therapies including the highest doses of the highest intensity statins and/or ezetimibe and/or PCSK9 inhibitors. Eight subjects (5 male and 3 female, all Caucasian, average age 53 years) were enrolled at sites in the US, Canada and Israel. Genetic analysis of the patients subsequently confirmed that 3 of them had no LDL receptor activity, the most severe form of HoFH, and that 5 had the more common HeFH. The trial, therefore, enrolled a broader FH population than originally planned.
Patients were administered oral gemcabene once daily, with dosage escalating from 300 mg to 600 mg and then 900 mg every 4 weeks, for a total duration of 12 weeks. On various baseline aggressive lipid lower therapies, the eight FH subjects had a mean baseline LDL-C level of 351 mg/dl prior to add-on gemcabene treatment. Treatment with gemcabene 600 mg, the Company’s target commercial dose, resulted in an absolute reduction of 93 mg/dL for the overall population and 92 mg/dL and 94 mg/dL for the HoFH and HeFH subjects, respectively. The results for the primary endpoint of mean percent change in LDL-C from baseline at each dose and related time point are presented below.
As shown the table below, gemcabene impacted multiple secondary endpoints, showing reductions from baseline in total cholesterol (TC), triglycerides (TG), non-HDL, apoB, apoE, high sensitivity C-Reaction Protein (hsCRP), and other relevant biomarkers. Importantly, gemcabene 600 mg showed a 33% reduction in hsCRP.
*Two subjects had acute events that were associated with elevation in hsCRP during the first dosing period and resolved prior to week 8.
Gemcabene’s Novel Mechanism of Action (MOA) Provides Benefit to Statin Resistant Patients
“The data from COBALT-1 further validate gemcabene’s novel MOA and its ability to be additive to statins and other lipid lowering therapies,” said Dr.
Three patients in the trial were intolerant to statins and two of these were HeFH patients. The LDL-C reductions in two of these three patients was 50% or higher. One patient was previously on stable lomitapide (Juxtapid®) for 3 years, then washed-out, prior to gemcabene as add-on to the patients’ baseline therapy. This individual experienced a 55% reduction in LDL-C. In the most difficult to treat subset of HoFH, patients with no LDL-C receptor activity, gemcabene demonstrated a response in 2 of 3 subjects, with a mean reduction across all 3 subjects of 15% with gemcabene 600 mg.
Safety was assessed by adverse event (AE) monitoring, clinical laboratory assessments, electrocardiograms, physical examinations and vital signs. AEs were mild to moderate in intensity across all doses of gemcabene and consistent with previously reported AEs. The majority of AEs were gastrointestinal. There were no serious AEs or withdrawals due to AEs in the COBALT-1 study. There was no evidence of hepatic or muscle injury in the study, including the 5 patients also taking statins.
“The data from COBALT-1 are very exciting,” said
It is estimated that up to 28% of HeFH patients have mixed dyslipidemia. Mixed dyslipidemia refers to a group of patients at high risk for cardiovascular disease that have elevated LDL-C, apolipoprotein B, and triglycerides. Gemphire believes that gemcabene offers a unique value proposition for those patients, based on its demonstrated ability to lower these three biomarkers.
The complete data for COBALT-1 will also be submitted for publication in a peer reviewed journal.
Gemcabene’s mechanism of action and safety profile are highly differentiated
Gemphire’s product candidate, gemcabene (CI-1027), 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 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 for 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 and improve insulin sensitization. Gemcabene is liver-directed and reduces apoC-III mRNA and plasma levels. Gemcabene also reduces acetyl-CoA carboxylase (ACC1) and CCR2/CCR5 receptor mRNA levels, which may have applications in non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD). Gemcabene has demonstrated proof of concept efficacy for NASH in the STAM™ model developed at
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 has initiated 3 clinical trials for homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH)/atherosclerotic cardiovascular disease (ASCVD), and severe hypertriglyceridemia (SHTG) under NCT02722408, NCT02634151, and NCT02944383, respectively with a fourth planned trial in NASH to initiate in the fourth quarter of 2017. Please visit www.gemphire.com for more information.
Forward Looking Statements
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