Data Support Clinical Evaluation of Gemcabene as
a Potential Treatment For NAFLD/NASH
Gemphire Therapeutics Inc. (NASDAQ:GEMP), a clinical-stage
biopharmaceutical company focused on developing and commercializing
therapies for cardiometabolic disorders, including dyslipidemia and
NASH, announced today the presentation of preclinical results
demonstrating proof of concept efficacy of gemcabene in a
well-established animal model of nonalcoholic steatohepatitis
(NASH). The results are featured in a poster presentation
today at The Liver Meeting®, the annual meeting of the Association
for the Study of Liver Diseases (AASLD), taking place in
Washington, D.C. Gemphire plans to initiate a clinical study
in patients suffering from fatty liver disease and NASH in the
fourth quarter of 2017. Approximately 6 million adult
patients in the U.S. are affected by NASH for which there is
currently no effective treatment available.
In this study, gemcabene was evaluated in the STAM™ mouse model
of NASH, in which diabetic mice fed a high fat diet rapidly develop
fatty liver disease. Animals were treated with either
gemcabene (at doses of 30, 100 and 300 mg/kg daily), a reference
drug telmisartan (Micardis®, Boeringer Ingelheim) or vehicle.
Key findings were as follows:
- At the highest dose level gemcabene-treated mice demonstrated a
significant histological reduction in Non-Alcoholic Fatty Liver
Disease (NAFLD) Activity Score (NAS). Gemcabene also showed
significant decreases in the fibrosis area at all doses compared to
the vehicle group.
- Gene expression analysis showed that, in animals treated with
100 and 300 mg/kg gemcabene, there was a statistically significant
decrease in mRNA expression levels of inflammation markers in the
liver (TNF-α, MCP-1, MIP-1β, CCR5, CCR2, NF- κB), suggesting
gemcabene hits multiple inflammatory targets and has a
hepatoprotective effect on liver pathology.
- Genes related to stellate cell activation and collagen and
fibrosis markers were down-regulated in this murine model of
NASH.
“The effects of gemcabene on the liver histology and gene
expression levels associated with inflammation revealed by this
study are complementary to the results observed in dyslipidemia
patients, and support our plans to move forward with the clinical
evaluation of gemcabene in NAFLD/NASH,” said Dr. Charles L.
Bisgaier, Co-founder and Chief Scientific Officer of Gemphire.
“Given what we know about gemcabene’ s ability to impact multiple
targets including LDL-C, triglycerides, CRP and the glucose
disposal rate in human clinical trials, we believe that gemcabene
may be a good clinical candidate for the treatment of
NAFLD/NASH. These attributes, combined with gemcabene’s
safety profile and lack of liver or muscle toxicities in completed
clinical trials, which included high-intensity statin therapies,
may provide gemcabene a unique advantage to the other treatments in
development for NAFLD/NASH,” concluded Dr. Bisgaier.
About NAFLD/NASH Nonalcoholic steatohepatitis
(NASH) is a severe disease of the liver caused by hepatocyte
inflammation and a buildup of fat in the organ. In the United
States, NASH affects approximately 2-5% of the population. An
additional 10-30% of Americans have fat in their liver, but no
inflammation or liver damage, a condition called NAFLD or “fatty
liver.” The underlying cause of NASH is unclear, but it most
often occurs in persons who are middle-aged and overweight or
obese. Many patients with NASH have elevated serum lipids,
diabetes or pre-diabetes. Progression of NAFLD/NASH can lead
to liver cirrhosis, fibrosis, hepatocellular carcinoma, liver
failure and liver-related death. Liver transplantation is
currently the only treatment for advanced cirrhosis with liver
failure. At this time, there are no FDA-approved treatments
for NAFLD/NASH.
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 also reduces
acetyl-CoA carboxylase (ACC1) and CCR2/CCR5 receptor mRNA levels,
markers involved in the progression of non-alcoholic
steatohepatitis (NASH)/non-alcoholic fatty liver disease
(NAFLD). Gemcabene has demonstrated proof of concept efficacy
for NASH in the rodent STAM™ model developed at SMC Laboratories in
Tokyo, Japan. Gemcabene has been tested as monotherapy and in
combination with statins and other drugs in 956 subjects across 20
Phase 1 and Phase 2 clinical trials. Given this profile of efficacy
across multiple pathological pathways, as well as evidence of
safety and tolerability, particularly when used as an add-on to
many other therapeutic drugs, gemcabene has attributes that support
studies in humans for NASH.
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 the fourth quarter 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,
regulatory submissions and meetings 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
December 31, 2016, Gemphire’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2017 and in other filings Gemphire makes
with the SEC from time to time. In addition, the
forward-looking statements included in this press release represent
Gemphire’s views as of the date hereof. Gemphire anticipates
that subsequent events and developments will cause Gemphire’s views
to change. However, while Gemphire may elect to update these
forward-looking statements at some point in the future, Gemphire
specifically disclaims any obligation to do so. These
forward-looking statements should not be relied upon as
representing Gemphire’s views as of any date subsequent to the date
hereof.
Contact:Andrew McDonald, Ph.D.LifeSci Advisors,
LLC(646) 597-6987
Jeff Mathiesen, CFOGemphire Therapeutics Inc.(734)-245-1700
Gemphire Therapeutics (NASDAQ:GEMP)
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