New analysis of data shows clinically meaningful
reductions in LDL-C and hsCRP across multiple trials and confirms
support to advance gemcabene into Phase 3
Gemphire Therapeutics Inc. (NASDAQ:GEMP), a
clinical-stage biopharmaceutical company focused on developing and
commercializing therapies for cardiometabolic disorders, including
dyslipidemia and NASH, today announced plans to advance its
product candidate gemcabene into Phase 3 development in 2018.
Gemcabene successfully achieved the primary endpoint in two
recently completed Phase 2b studies, COBALT-1 and ROYAL-1, and the
Company is now preparing for end of Phase 2 meetings with both the
US Food and Drug Administration (FDA) and European Medicines Agency
(EMA), anticipated to take place in early 2018. The primary
focus of these meetings is to reach agreement on the design of the
Phase 3 development programs for its hypercholesterolemia
indications. Twenty clinical studies have shown gemcabene to be
safe and effective as monotherapy or in combination with all
current treatments for hypercholesterolemia, including the highest
intensity statins, PCSK9 inhibitors and ezetimibe, and thus appears
to be beneficial for high-risk patients that have not achieved
lipid goals.
Gemphire is developing gemcabene as an add-on therapy to diet
and maximally-tolerated statins for the treatment of several
hypercholesterolemic populations, including atherosclerotic
cardiovascular disease (ASCVD), with an emphasis on the high risk
cardiometabolic subset of ASCVD patients, heterozygous familial
hypercholesterolemia (HeFH) and homozygous familial
hypercholesterolemia (HoFH). The Company also plans to
develop gemcabene as monotherapy or as add-on therapy to diet and
other lipid lowering therapies for the treatment of severe
hypertriglyceridemia (SHTG). Gemcabene has been shown to be safe
and effective in combination with all current treatments for
hypercholesterolemia, including the highest intensity statins,
PCSK9 inhibitors and ezetimibe.
“I believe we have accumulated a compelling body of clinical
data demonstrating the ability of gemcabene to reduce low density
lipoprotein cholesterol (LDL-C) in both orphan and broad
dyslipidemic conditions,” said Dr. Steven Gullans, Interim CEO
of Gemphire. “Gemcabene is a unique late stage clinical asset
and the only compound in development across the full spectrum of
dyslipidemia that targets the triple threat of LDL-C, inflammation
and triglycerides (TG). We look forward to reviewing these data
with the FDA and EMA to seek agreement on the design of our
comprehensive Phase 3 clinical program to confirm the benefits
observed in prior studies and to support regulatory approval for
the various indications and commercialization in the major
markets.”
“Many high-risk patients are unable to achieve optimal LDL-C
reductions and levels with the currently available therapies,” said
Evan Stein, MD Director Emeritus of the Metabolic &
Atherosclerosis Research Center, in Cincinnati, Ohio. “As
such, physicians and patients need additional options that can be
combined safely with statin therapy, which is the first therapy
utilized for most patients, and can provide additional efficacy
across multiple parameters associated with cardiovascular
risk. Given the recent data released by Novartis Inc.
establishing reduction of inflammation and hsCRP as a novel
mechanism to decrease cardiovascular disease (CVD), the combined
effect of gemcabene on LDL-C, apolipoprotein B and hsCRP is very
promising for patients at high risk for CVD events.”
New Analysis Shows That 600 mg of Gemcabene Reduced
LDL-C by 21% in Hypercholesterolemic Patients and by 25% in Mixed
Dyslipidemic Patients across Multiple Clinical Trials
The Company has performed an extensive analysis of data on
hypercholesterolemic patients across previously completed clinical
trials for gemcabene, including the most recently completed
COBALT-1 and ROYAL-1 studies. In addition to the LDL-C
reduction in the overall cohorts, efficacy was assessed according
to baseline LDL-C levels, and other baseline characteristics, such
as the degree of obesity, magnitude of HbA1c, mixed dyslipidemia,
level of inflammation, a responder analysis and combinations of
these factors.
Data for the ROYAL-1 study have been accepted for presentation
at the American Heart Association’s (AHA) Scientific Sessions in
November 2017. Details of the ROYAL-1 data are embargoed
until presentation at AHA; however, the additional analyses of
ROYAL-1 showed similar trends as we will outline from the combined
analysis below. As such, the announcement today is focusing
on the combined analysis of the hypercholesterolemic patients
involved in previously completed clinical studies.
Patients were included in the combined analysis if they were
hypercholesterolemic and were on stable statin and/or other lipid
lowering therapy, which represents the intended use for gemcabene
in clinical practice for its hypercholesterolemic indications. The
prior clinical trials included 352 hypercholesterolemic patients,
composed of placebo (n=110) and gemcabene 150 mg (n=23), 300 mg
(n=61), 600 mg (n=94) and 900 mg (n=64) dose groups. Data from the
gemcabene 600 mg dose group are presented in the table below since
this is the intended target dose for the Phase 3 trials for the
reduction of LDL-C across the hypercholesterolemic patient
population.
Gemphire believes gemcabene offers a unique value proposition
for those patients with a high-risk cardiometabolic profile,
specifically those with obesity, pre-diabetes /diabetes,
inflammation and/or mixed dyslipidemia. Mixed dyslipidemia refers
to a group of patients at high risk for cardiovascular disease that
have elevated LDL-C, apolipoprotein B, and TGs. Cardiovascular
demographics from the National Health and Nutritional Health
Examination Survey (NHANES) data estimate that of the approximately
40 million patients on statins, approximately 6.1 million represent
cardiometabolic patients who are not at goal and have LDL levels
above 70 mg/dL with approximately 3 million of these patients being
above 100 mg/dL. Cardiometabolic patients usually have several
lipid abnormalities that can benefit from gemcabene’s ability to
lower LDL-C, hsCRP and TGs. The LDL-C reductions for mixed
dyslipidemic patients who received 600 mg of gemcabene or placebo
are presented separately in the table below.
Combined results from
hypercholesterolemic patients across completed clinical
studies |
All Hypercholesterolemic Subjects |
Gemcabene 600 mg
n= 94 |
Placebo n=110 |
p value |
LDL-C reduction |
-21% |
-5% |
p<0.0001 |
Mixed Dyslipidemia Subset (Baseline LDL-C ≥100
and TGs ≥200 and <500 mg/dL) |
Gemcabene 600
mg (high risk
patients) n= 24 |
Placebo (high risk
patients) n=
30 |
p value |
LDL-C reduction |
-25% |
-4% |
p=0.0002 |
Ability of Gemcabene to Reduce hsCRP and Inflammation is
Potentially a Key Differentiator
Elevated serum C-Reactive Protein (hsCRP) is a known biomarker
for patients at increased risk of a cardiovascular event. As
reported previously in the ROYAL-1 study, 600 mg of gemcabene
lowered serum hsCRP by 40% (n=51) compared to 6% for placebo (n=51)
(p<0.0001). Note that this effect was additive to the
reduction of hsCRP provided by statins, as the ROYAL-1 patients
were already taking maximally tolerated doses of statins.
From the combined analysis in hypercholesterolemic patients the
median hsCRP reduction for patients on gemcabene 600 mg was 40%
(n=90) compared with 5% in the placebo group (n=108)
(p<0.0001).
CRP is a plasma protein biomarker secreted into the blood from
the liver in response to inflammation. Reducing this biomarker is
associated with a reduction in cardiovascular risk, as confirmed by
Novartis Inc.’s Canakinumab Anti-inflammatory Thrombosis Outcomes
Study (CANTOS) recently presented at the European Society of
Cardiology (ESC) congress in Barcelona, Spain, in August of this
year. As reported by Novartis Inc. in August 2017, in the
CANTOS study, patients with a history of myocardial infarction and
elevated hsCRP received treatment with an injectable
anti-inflammatory monoclonal antibody to the cytokine IL-1β to
determine the direct potential impact of reducing inflammation on
cardiovascular events. The results demonstrated that reducing
inflammation as measured by hsCRP (with a median hsCRP reduction of
37%) led to a 15% reduction in cardiovascular related MACE
(combination of non-fatal myocardial infarction, non-fatal stroke
and cardiovascular death). The impact of orally administered
gemcabene on hsCRP and inflammation remains a potentially key
differentiator from other compounds that are approved or in
development as add-on therapy to maximally tolerated statins.
Gemcabene Appears Safe for High Risk Patients in
Combination with Maximally Tolerated Statins and Other Approved
Treatments
The COBALT-1 and ROYAL-1 trials were designed to determine the
safety, tolerability and efficacy of gemcabene as an add-on to the
highest doses of statins (e.g., rosuvastatin 20 and 40 mg and
atorvastatin 40 and 80 mg doses; moderate intensity therapies were
also included), as well as PCSK9 inhibitors, and ezetimibe.
We believe the results from all 20 clinical studies in which 956
patients were exposed to gemcabene have demonstrated that gemcabene
is well tolerated and safe. Although in practice, most patients are
on low and moderate intensity statins, in our clinical trials
gemcabene demonstrated a clean safety profile even when combined
with the highest doses of the high intensity statins, simvastatin,
atorvastatin and rosuvastatin. To date, there has been no evidence
for hepatic or muscle related toxicities and no serious adverse
events related to gemcabene treatment. Overall treatment
emergent adverse events for gemcabene have been similar to
placebo. Most adverse events have been mild to moderate in
intensity and the most commonly reported adverse events have been
infection and headache (based on occurrence in > 5% of subjects
on gemcabene, although the rate for infection was less than
placebo).
Gemphire’s Commitment to Cardiometabolic Patients,
Physicians and Payors
Cardiovascular disease remains the leading cause of death
globally despite the availability of statins and other
therapeutics. In addition, the large recent increases in the
prevalence of obesity and diabetes will result in a much greater
number of individuals at risk for cardiovascular and liver
diseases, including NASH. The highest risk patients would
benefit from a new therapy that can be added safely to all commonly
prescribed statins at any dose. Gemcabene has been given to
over 950 patients to date and it appears to be a safe and effective
therapeutic option for millions of cardiometabolic patients who are
already on maximally-tolerated statins to reduce LDL-C, hsCRP and
other potentially atherogenic lipid particles. As a once daily oral
therapy at an affordable price point, gemcabene has the potential
to be a valuable new approach that will provide benefits to
patients, physicians and payors.
“Gemcabene has demonstrated efficacy across a broad array of
important lipid parameters, such as LDL-C, non-HDL-C, total
cholesterol, apolipoprotein B and triglycerides, that have been
associated with cardiovascular events, such as heart attacks,
stroke and death. Gemcabene has also demonstrated significant
effects on reducing hsCRP, a marker of inflammation, which may be
an important new target of therapy in patients with cardiovascular
disease, based on the CANTOS trial results. Importantly,
gemcabene has demonstrated an excellent safety profile without
evidence of hepatic or muscle toxicities, even when combined with
the most potent statins,” stated Dr. Lee Golden, Chief Medical
Officer of Gemphire.
COBALT-1 study to be presented at the FH Foundation’s
Summit
Gemphire will also be announcing full results of the COBALT-1
(HoFH) study at the FH Foundation’s Summit meeting in Miami,
Florida on Monday, September 25th at 9:00 am ET. The results
will be presented by Dr. Marina Cuchel, MD, PhD, Research Associate
Professor at the Perelman School of Medicine at the University of
Pennsylvania. The FH Summit is an invitation-only event that
convenes global experts within various fields to tackle the most
pressing issues facing FH populations today. The 2017 FH Global
Summit will include topics on the challenges and opportunities of
diverse FH subpopulations navigating diagnosis, care and access.
For more information, refer to
https://thefhfoundation.org/event/2017-fh-global-summit.
Gemphire to Soon Launch Proof of Concept Program in
NASH
As previously announced, Gemphire will be initiating its proof
of concept study in patients that suffer from fatty liver disease
and nonalcoholic steatohepatitis (NASH) in the fourth quarter of
2017. Unmanaged cardiometabolic disease is the underlying
cause of atherosclerosis and fatty liver disease. Gemcabene’s
unique mechanism of action has demonstrated positive attributes
that may be protective to both the heart and liver. Approximately 6
million patients in the U.S. are affected by NASH for which there
is currently no effective treatment available.
Conference Call and Webcast
Gemphire management will host a conference call for investors at
4:30 pm ET today. To participate, please dial (844) 494-0188
(domestic) or (425) 278-9114 (international) and reference
conference ID 86185879. A webcast replay will be available on the
News & Events section of the Gemphire website for all
interested parties following the call and will be archived and
available for 90 days.
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 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,
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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