COBALT-1 results show significant LDL-C lowering
for FH patients, including a mean reduction in LDL-C of 39% in the
HeFH population
Gemphire Therapeutics Inc. (NASDAQ:GEMP), a clinical-stage
biopharmaceutical company focused on developing and commercializing
therapies for cardiometabolic disorders, including dyslipidemia and
NASH, announced the presentation today of their open-label
Phase 2b COBALT-1 clinical data at the 2017 FH Global Summit,
taking place in Miami, Florida from September 24-25, 2017. As
previously announced, COBALT-1 achieved its primary endpoint,
showing a statistically significant reduction in LDL cholesterol
(LDL-C) in gemcabene-treated patients, compared to baseline at 12
weeks (p=0.0035). The additional data being presented today show
that gemcabene is efficacious in both Homozygous Familial
Hypercholesterolemia (HoFH) and Heterozygous Familial
Hypercholesterolemia (HeFH) patients.
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. Steven
Gullans, Interim CEO of Gemphire Therapeutics. “The results
show that gemcabene is efficacious, and very importantly, it is
also safe and well-tolerated, even when used on top of the highest
prescribed doses of cholesterol lowering medications, including
statins. The types of patients enrolled in this study reflect a
subgroup of very high-risk Familial Hypercholesterolemic (FH)
patients who comprise a market of approximately one million
patients in the U.S. We look forward to sharing these data with the
FDA and EMA in our planned end of Phase 2 meetings and to advancing
gemcabene into Phase 3 trials in FH in 2018.”
“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. Joshua Knowles Chief Medical Advisor for the FH Foundation. “We
are very encouraged to see the positive results that have been
achieved with gemcabene presented today at the 2017 FH Global
Summit.”
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.
Primary Endpoint: Change in LDL-C mg/dL Levels
by Dose of Gemcabene |
|
300 mg, week 4 |
600 mg, week 8 |
900 mg, week 12 |
Overall population (n=8) |
-25%p=0.0063 |
-30%p=0.0047 |
-29%P=0.0035 |
HeFH (n=5) |
-34%p< 0.0001 |
-39%p< 0.0001 |
-40% p< 0.0001 |
HoFH (n=3) |
-10%p=0.3601 |
-15%p=0.1920 |
-12%p=0.2912 |
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.
Secondary Endpoints For Overall
Population |
|
Baseline Level
(SD) |
Mean Change by Dose of
Gemcabene (% Change from Baseline)
|
300 mg, week 4 |
600 mg, week 8 |
900 mg, week 12 |
Total Cholesterol (mg/dL) |
425.4 (167.1) |
-21.3 |
% |
-24.6 |
% |
-24.6 |
% |
Non-HDL-C (mg/dL) |
379.9 (177.3) |
-23.8 |
% |
-27.2 |
% |
-26.5 |
% |
ApoB (mg/dL) |
221.3 (97.3) |
-18.8 |
% |
-24.8 |
% |
-22.4 |
% |
ApoE (mg/dL) |
6.7 (1.7) |
-19.5 |
% |
-23.0 |
% |
-19.2 |
% |
ApoC-III (mg/dL) |
10.6 (4.1) |
-7.8 |
% |
-9.7 |
% |
-6.5 |
% |
VLDL-C (mg/dL) |
28.7 (12.5) |
-13.5 |
% |
-8.4 |
% |
-7.2 |
% |
Triglycerides (mg/dL) |
143.6 (62.7) |
-12.6 |
% |
-9.01 |
% |
-7.2 |
% |
HDL-C (mg/dL) |
45.4 (18.7) |
-11.89 |
% |
-13.3 |
% |
-12.9 |
% |
hsCRP* (mg/L) |
3.75 |
38.7 |
% |
-33.3 |
% |
-45.3 |
% |
*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. Charles Bisgaier, Gemphire’s Chief
Scientific Officer and Co-Founder. “Our studies of gemcabene’s MOA
suggest it can reduce LDL levels by accelerating the clearance of
VLDL remnants, through the VLDL remnant receptor (syndecan-1). In
addition, gemcabene appears to decrease apoC-III in liver by
lowering mRNA levels which would also facilitate VLDL clearance
through the remnant receptor. Furthermore, gemcabene appears to
reduce LDL-C by inhibiting triglyceride and cholesterol synthesis
thereby reducing liver VLDL production. Hence, gemcabene’s MOA
appears to be synergistic with statins because it acts through a
different pathway by enhancing VLDL clearance via upregulation of
the remnant VLDL receptor whereas statins act by up-regulating the
LDL-C receptor.”
Dr. Lee Golden, Gemphire’s Chief Medical Officer, stated, “It
was very encouraging to see clinically meaningful reductions in
LDL-C along with concordant reductions in other important lipid
parameters, such as non-HDL and apolipoprotein B, in these
patients. Targeting inflammation was recently shown, in the CANTOS
study, to improve clinical outcomes in high risk cardiovascular
patients, and treatment with gemcabene at 600 mg and 900 mg
demonstrated a 33% and 45% reduction in hsCRP, respectively. Given
that hsCRP is an accepted marker of inflammation that is associated
with an increased risk for cardiovascular events, gemcabene may
provide multiple levels of benefit to FH patients.”
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 John Kastelein,
MD, Professor of Medicine, Department of Vascular Medicine,
Academic Medical Center/University of Amsterdam, The
Netherlands. “Familial hypercholesterolemia patients are at
high-risk for having premature cardiovascular events, such as heart
attacks and strokes, and gemcabene offers a potentially novel
mechanism for physicians to help these patients further reduce
their LDL-C. Gemcabene provided a 15% LDL-C reduction in the
most difficult HoFH patients to treat, those with a completely
defective LDL-C receptor. Safety of new therapies when
combined with potent statins and other lipid lowering therapies is
very important in FH and other hypercholesterolemic patients, and
gemcabene has been well tolerated, without any evidence for
drug-drug interactions.”
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.
About the FH Foundation
The FH Foundation (www.thefhfoundation.org) is a
patient-centered nonprofit organization dedicated to research,
advocacy, and education of Familial Hypercholesterolemia (FH). The
Foundation’s mission is to raise awareness and save lives by
increasing the rate of early diagnosis and encouraging proactive
treatment. The annual FH Global Summit convenes global experts
within various fields to tackle the most pressing issues facing FH
populations today. The 2017 FH Global Summit, taking place in
Miami, Florida, September 24-25, focuses on the challenges and
opportunities of navigating diagnosis, treatment and access across
diverse FH populations.
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 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 and has demonstrated promising
evidence of efficacy, safety and tolerability.
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)
Historical Stock Chart
From Jun 2024 to Jul 2024
Gemphire Therapeutics (NASDAQ:GEMP)
Historical Stock Chart
From Jul 2023 to Jul 2024