Gemphire Announces Top-Line Data from COBALT-1 Phase 2b Clinical Trial in HoFH Patients
Gemcabene achieves primary endpoint for LDL cholesterol in phase 2b HoFH trial
Company to host conference call at
COBALT-1 enrolled patients clinically or genetically diagnosed as HoFH, who were on a variety of background therapies including the highest doses of statins and/or ezetimibe and/or PCSK9 inhibitors. These therapeutic classes represent the current initial drug therapies for HoFH. Eight subjects (5 male and 3 female, all Caucasian, average age 53 years) on previously prescribed therapy (which included statins, ezetimibe, evolocumab, cholestyramine, and omega-3 fatty acids) were enrolled from sites in the US,
The mean baseline LDL-C was 351 mg/dL (range from 138-623 mg/dL). Gemcabene 300 mg lowered LDL-C by a mean of 25% (p=0.0063; range -55% to +1%), gemcabene 600 mg lowered LDL-C by a mean of 30% (p=0.0047; range -51% to +2%), and gemcabene 900 mg lowered LDL-C by a mean of 29% (p=0.0035; range -54% to +6%). The complete data for COBALT-1 will be submitted to a cardiovascular conference for presentation, as well as for publication in a peer reviewed journal.
Adverse events (AEs) were mild to moderate in intensity across all doses of gemcabene and consistent with previously reported AEs. There were no serious AEs or withdrawals due to AEs in the COBALT-1 study.
"We are excited by these results from our COBALT-1 Phase 2b trial in HoFH patients," said
COBALT-1 was designed to evaluate the LDL-C lowering efficacy of gemcabene in up to 8 patients with either genetic confirmation or a clinical presentation of HoFH on a stable low-fat, low cholesterol diet in combination with a pre-existing, regulatory-approved, lipid-lowering therapy for at least 4 weeks prior to treatment. Patients were excluded if they were undergoing apheresis or taking mipomersen or lomitapide. All enrolled patients were further evaluated for known DNA mutations causing HoFH. The primary endpoint for each dose of gemcabene (300, 600 and 900 mg) was mean percent change in LDL-C from baseline at 4, 8, and 12 weeks respectively. Secondary endpoints include mean percent change from baseline in hsCRP, apoB, non-HDL-C, TG, VLDL-C and total cholesterol. Safety was being assessed by AE monitoring, clinical laboratory assessments, electrocardiograms, physical examinations and vital signs.
“These data announced today continue to demonstrate the additive lipid lowering efficacy of gemcabene that has been demonstrated in the extensive clinical program to date,” said
Additional analyses of 6 subjects that met the more stringent
“The overall reductions in LDL-C, and in particular more than 20% in the subgroup that met the
“These data suggest that gemcabene can offer important additional add-on LDL-C reduction to approved therapies for HoFH patients,” said
In 2014, gemcabene was granted Orphan Drug Designation for HoFH by the US FDA. Additional information on the COBALT-1 trial, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier NCT02722408.
In addition to these phase 2 results from COBALT-1 (Trial 19) reported here today, gemcabene is currently being evaluated for LDL-C lowering on top of high- and moderate intensity statins in heterozygous familial hypercholesterolemic (HeFH)/atherosclerotic cardiovascular disease (ASCVD) patients in ROYAL-1 (Trial 20) and for the reduction in triglyceride levels in a severe hypertriglyceridemia (SHTG) patient population in INGIGO-1 (Trial 21).
Conference Call and Webcast
Gemphire will further review the top-line data from the COBALT-1 Phase 2b clinical trial in HoFH patients in a conference call today at
About HoFH
HoFH is a rare genetic disease that is most commonly caused by a mutation in both alleles of the LDL receptor gene responsible for removing LDL from the blood. As a result of having defective or deficient LDL receptor function, HoFH patients exhibit severely high LDL-C levels, are at very high risk of experiencing premature cardiovascular events, such as a heart attack or stroke, and develop premature and progressive atherosclerosis. LDL-C levels in untreated HoFH patients are typically in the range of 500 mg/dL to 1,000 mg/dL, compared to a normal target range of 70 mg/dL to 100 mg/dL. Unless treated, most patients with HoFH do not survive beyond 30 years of age. There are approximately 300 to 2,000 HoFH patients in
Currently approved widely available treatments for patients with HoFH include statins, ezetimibe, other approved LDL-C lowering therapies (such as bile acid sequestrants), injectable PCSK9 inhibitor Repatha®, and in some countries novel drugs mipomersen (KYNAMRO®) or lomitapide (Juxtapid®) which both include boxed warnings for liver toxicity. HoFH patients usually also require LDL apheresis when available. Despite the availability of various treatments which combined may lower LDL-C 40-45%, many patients are still unable to achieve recommended LDL-C levels.
About Gemcabene
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 enhances 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 VLDL-C, LDL-C, 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
About Gemphire
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 second half of 2017. Please visit www.gemphire.com for more information.
Forward Looking Statements
Any statements in this press release about Gemphire’s future expectations, plans and prospects, including statements about Gemphire’s financial prospects, future operations and sufficiency of funds for future operations, clinical development of Gemphire’s product candidate, expectations regarding future clinical trials and future expectations and plans and prospects for Gemphire, expectations regarding operating expenses and cash used in operations, and other statements containing the words "believes," "anticipates," "estimates," "expects," "intends," "plans," "predicts," "projects," "targets," "may," "potential," "will," "would," "could," "should," "continue," “scheduled” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the success and timing of Gemphire’s regulatory submissions and pre-clinical and clinical trials; regulatory requirements or developments; changes to Gemphire’s clinical trial designs and regulatory pathways; changes in Gemphire’s capital resource requirements; Gemphire’s ability to obtain additional financing; Gemphire’s ability to successfully market and distribute its product candidate, if approved; Gemphire’s ability to obtain and maintain its intellectual property protection; and other factors discussed in the "Risk Factors" section of Gemphire’s Annual Report on Form 10-K for the year ended
Contact:Andrew McDonald , Ph.D.LifeSci Advisors, LLC (646) 597-6987Jeff Mathiesen , CFOGemphire Therapeutics Inc. (734) 245-1700