FDA requests the Company provide additional data
regarding the partial clinical hold
Gemphire Therapeutics Inc. (NASDAQ: GEMP), a clinical-stage
biopharmaceutical company focused on developing and commercializing
therapies for cardiometabolic disorders, including dyslipidemia and
nonalcoholic steatohepatitis (NASH), today announced that the
U.S. Food and Drug Administration (FDA) has requested that the
Company produce data from a sub-chronic toxicology study to provide
information to support lifting the partial clinical hold on
gemcabene with respect to clinical trials of longer than six months
in duration. The FDA also informed the Company that the End of
Phase 2 meeting, and consequently the initiation of Phase 3 trials
investigating gemcabene in dyslipidemia indications and long-term
safety exposure trials needed for registration, will not take place
until the partial hold has been lifted.
Gemphire’s ongoing Phase 2a proof-of-concept (POC) studies
investigating gemcabene as a treatment for familial partial
lipodystrophy (FPL) and for pediatric NAFLD are not affected by the
FDA’s request for additional data and the Company continues to
expect that these studies will produce top-line interim data in
late 2018 and in the first half of 2019, respectively. In addition,
the Company continues to be free to conduct clinical trials that do
not extend beyond six months in duration.
Beginning in 2004, the FDA began issuing partial clinical holds
to all sponsors of PPAR agonists or agents deemed to have PPAR-like
properties from preclinical studies. The FDA takes the position
that PPAR agonists are potential liver toxins, but recognizes that
rodent observations are often not relevant to humans. In 2004, the
FDA determined that gemcabene has PPAR agonist properties and
issued a partial clinical hold. The partial clinical hold permits
clinical trials of up to six months for gemcabene and also required
the Company to conduct two-year rat and mouse carcinogenicity
studies that are reviewed by the agency in view of all other
preclinical data and completed clinical trials before allowing
clinical trials of longer than six months.
As previously disclosed, we believe gemcabene acts through PPARα
to cause peroxisome proliferation and tumor formation in rodents
and these effects are likely rodent-specific phenomena. Based on
historical nonclinical and clinical experience on these type of
compounds, we believe rodents share little apparent relevance for
human risk assessment. In recently completed PPAR agonist receptor
binding assays, we observed weak or no gemcabene direct binding to
the mouse, rat, or human PPARα, PPARβ/d, or PPARγ receptors. We
have also observed that gemcabene induces markers of peroxisome
proliferation in wild-type mice but not in PPARα knockout mice. We
believe the PPARα responses in rats and mice are secondary and
perhaps related to the mobilization or formation of a naturally
occurring molecule that binds to PPARα in response to gemcabene
administration.
The Company recently submitted the results of the two-year rat
and mouse carcinogenicity studies to the FDA. As would be expected
for an activator of PPARα, the results showed the presence of liver
tumors. The Company also provided results from a short-term, 8 day
study demonstrating that in PPARα knockout mice, gemcabene did not
induce known markers of peroxisome proliferation, providing
evidence that gemcabene works through PPARα. Similar observations
in PPARα knockout mice have been seen with other agents, such as
gemfibrozil, that cause tumors in rodents but not in humans.
In response the FDA has requested that, as part of a complete
response, Gemphire must provide additional data including a
subchronic (13 week) study in PPARα knock-out mice and PPAR
transactivation assays using monkey and canine PPAR isoforms, to
further understand the human relevance of the preclinical findings.
The Company has initiated plans to conduct these required studies
and expects to submit the additional results to the FDA in the
second quarter of 2019.
“We are working closely with the FDA to release the partial
clinical hold on gemcabene, with the goal of proceeding to an End
of Phase 2 meeting and reaching agreement on the design of a Phase
3 clinical program,” said Dr. Steven Gullans, CEO of Gemphire.
“Our confidence in gemcabene’s safety profile is supported by the
fact that it has been observed to be safe in nearly 1,200 human
subjects in 24 Phase 1 and 2 clinical trials. In fact, gemcabene’s
safety performance in previous human clinical provided the basis
for the FDA to allow the agent to be evaluated in a multi-center,
investigator-led ongoing NAFLD trial in pediatric patients.
“In the meantime, we are continuing to execute on our ongoing
Phase 2a POC clinical trials of gemcabene in NAFLD/NASH. Gemphire
is well capitalized, with $28 million cash on hand as of June 30
2018. Based on current projections, taking into account the delay
of significant cash expenditures for clinical trials and
manufacturing and the amended terms of the loan agreement with SVB,
we believe we have sufficient resources to fund operations into the
fourth quarter of 2019.”
Amended loan agreement with SVB
On July 31, 2018, Gemphire amended its loan agreement with
Silicon Valley Bank (“SVB”) to provide additional flexibility to
the Company. The original agreement established a term loan
facility of up to $15 million in aggregate principal amount to be
funded in up to three tranches. The Company received the first two
tranches, $10 million in aggregate, in July 2017.
Among other provisions, the loan amendment with SVB:
- Extends the date by which the FDA must lift the 6-month partial
clinical hold from July 31, 2018 to September 30, 2019 for purposes
of the requirement to provide cash security to SVB or prepayment of
the loan, which could also be required if the Company’s
unrestricted cash balance falls below a minimum amount prior to
such time.
- Extends the date that the third tranche of $5 million is
available for draw down by the Company to November 30, 2018, should
the conditions set forth in the amended loan agreement be met by
such date.
- Extends the interest-only monthly payment period from August 1,
2018 to November 1, 2018, which may be subject to further extension
if certain conditions set forth in the loan agreement are met.
For further details on the amendment to the loan agreement with
SVB, refer to our Current Report on Form 8-K filed with the
Securities and Exchange Commission on August 6, 2018.
Second Quarter Financial Results
Gemphire plans to announce its financial results for the second
quarter ending June 30, 2018 after market close on Monday, August
13.
Conference Call The Company will host a
conference call today Monday, August 6, at 4:30 pm Eastern Time. To
access the audio conference, please dial (844) 494-0188 (domestic)
or +1 (425) 278-9114 (international) and reference conference ID
1056909. 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.
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’s Phase 2 clinical program is
evaluating the efficacy and safety of gemcabene in
hypercholesterolemia, including FH and ASCVD, SHTG and NASH/NAFLD.
Two trials supporting hypercholesterolemia and one trial in SHTG
have been completed under NCT02722408, NCT02634151 and NCT02944383,
respectively, and the Company has initiated two proof-of-concept
trials for NAFLD/NASH. Please visit www.gemphire.com for
more information.
Forward Looking Statements Any statements
in this press release about Gemphire’s future expectations,
milestones, goals, 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,
expected timing of top-line results of such trials, timing and
expectations for regulatory submissions and meetings and future
expectations and plans and prospects for gemcabene, expectations
for the future competitive environment for gemcabene, expectations
regarding operating expenses and cash used in operations, and other
statements containing the words "believes," "anticipates,"
"estimates," "expects," "intends," "plans," "predicts," "projects,"
“promising,” "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:
developments in the capital markets, 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; the actions of
Gemphire’s competitors; 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 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:Ashley RobinsonLifeSci Advisors,
LLC(617) 535-7742
Jeff Mathiesen, CFOGemphire Therapeutics Inc.(734) 245-1700
Gemphire Therapeutics (NASDAQ:GEMP)
Graphique Historique de l'Action
De Mai 2024 à Juin 2024
Gemphire Therapeutics (NASDAQ:GEMP)
Graphique Historique de l'Action
De Juin 2023 à Juin 2024