- Histological improvement in fibrosis (≥1 stage) was
demonstrated in 39% of subjects according to NASH CRN, in 61% of
subjects by ranked assessment with a highly statistically
significant (p<0.0001) reduction in fibrosis score demonstrated
using AI-assisted, digital pathology reading
- Highly statistically significant (p<0.0001) reduction in
liver stiffness by Fibroscan
- Highly statistically significant (p<0.0001) reduction in
biochemical markers of liver injury ALT and AST
- Highly statistically significant reductions in major fibrosis
biomarkers: FIB-4 (p<0.0001), Pro-C3 (p<0.0001) and ELF (p=
0.0038) at week 24
- Galmed is submitting all data to the FDA to initiate
discussions on incorporating more sensitive histology reading
methodologies as primary endpoints in NASH clinical studies and is
actively looking for partnering opportunities to continue
Aramchol's clinical development.
TEL
AVIV, Israel, Jan. 4,
2023 /PRNewswire/ -- Galmed Pharmaceuticals Ltd. (NASDAQ:
GLMD) ("Galmed" or the "Company"), a clinical-stage
biopharmaceutical company for liver, metabolic and inflammatory
diseases reported today full results from the Open-Label Part of
the ARMOR study corroborating effects of Aramchol across all
efficacy parameters.
The study enrolled 157 subjects with biopsy-proven NASH
randomized 1:1:1 into three groups differing in the timing of the
post-baseline liver biopsy (Week 24, Week 48, and Week 72).
Fifty-one (51) subjects underwent post-baseline biopsies prior to
study discontinuation (28 subjects at <48 weeks and 23 subjects
at ≥48 weeks). The study was designed to assess the safety,
pharmacokinetics (PK) and efficacy kinetics as a function of
treatment duration. Three independent pathologists and three
different histopathology reading methodologies were used to assess
the antifibrotic effect of Aramchol: fibrosis stage based on NASH
CRN; ranked assessment (improvement/worsening/stable) of paired
(pre- and post-baseline) biopsies, blinded to sequence; and an
automated and continuous score of Fibrosis Composite Severity
(FCS), using FibroNest™, a quantitative AI digital pathology image
analysis method. Noninvasive tests (NITs) included imaging
(fibroscan) and biomarkers (liver enzymes, FIB-4, Pro-C3 and
ELF).
Aramchol treatment resulted in a high proportion of subjects
showing fibrosis improvement based on all three biopsy reading
methodologies, with a larger treatment effect with longer duration
of therapy. Following a treatment duration of 48 weeks or more,
improvement in fibrosis was demonstrated in 39% of subjects
according to NASH CRN and 61% of subjects according to ranked
assessment. At Week 48 AI demonstrated fibrosis improvement in 100%
of subjects when responders were defined by an absolute reduction
of the FCS score >0.3, 65% when responders were defined by a
relative reduction of >25%, and a statistically significant
reduction from baseline in mean FCS score (p<0.0001). NASH
resolution without worsening of fibrosis was demonstrated in 26.5%
of subjects.
Fibroscan, ALT, AST, and FIB4 were analyzed using MMRM, based on
all subjects (N=154). Fibroscan results were consistent, with an
improvement in fibrosis showing a mean absolute reduction from
baseline to week 72 of 2.5 kPa (p<0.0001). At Week 72, ALT was
reduced by 22 U/L (p<0.0001), AST
was reduced by 18 U/L (p<0.0001), and FIB-4 was reduced by 0.30
(p<0.0001).
Pro-C3 and ELF were analyzed for 43 subjects at week 24 showing
reduction in both Pro-C3 levels (p<0.0001) and ELF
(p=0.0038).
The Open Label part demonstrated the good safety profile of
Aramchol 300mg BID including long-term follow up. The incidence of
serious adverse events (SAEs) was consistent with the population
(10.4%) and early discontinuation rates due to adverse events (AEs)
were low (4.5%).
Prof. Vlad Ratziu, ARMOR study co-Principal investigator
commented: "The strength of the data we present today is in its
internal consistency and coherence. Effects of Aramchol are
demonstrated across all efficacy parameters with improvement over
time. We used an extremely rigorous pathology reading methodology
with three independent readers and three different morphological
assessments of fibrosis, including digital pathology, all
corroborating the antifibrotic activity of Aramchol".
Prof. Ratziu concluded that "The type and magnitude of effects
we see with Aramchol compared to other NASH candidates, together
with its unique mechanism of action and safety, potentially
position Aramchol as a leading treatment for patients with
NASH".
Allen Baharaff, Co-founder, President and CEO of Galmed added
"the study answered the key questions it set up to answer:
Aramchol's anti-fibrotic effects are seen across measures, a longer
treatment duration improves outcomes and the safety profile of the
300mg BID dose regimen remains good. Importantly, we clearly
demonstrated the challenges and opportunities of different
pathology reading methodologies and are prepared to discuss with
the FDA incorporating more sensitive methodologies as primary
endpoints in NASH clinical studies. This can have a critical impact
on the expected variability and sample size of future NASH studies.
As we continue to evaluate our strategic alternatives, the
advancement of Aramchol into the Double-Blind part of the ARMOR
study depends on the outcome of this process and at present we do
not have plans to initiate the Double-Blind part of the study".
About ARMOR Study
ARMOR is a Phase 3 study comprised of two-parts, an open-label
part and a randomized, double-controlled, placebo part, designed to
evaluate the safety and efficacy of Aramchol in approximately 200
sites in the U.S., Europe and Latin America.
The first part, an open-label study, was designed to evaluate
treatment response kinetics, pharmacokinetics and safety of twice
daily administration of Aramchol 300mg (new dosing regimen with
higher exposure) in approximately 150 subjects with NASH and liver
fibrosis stage 1-3 (F1 capped at 30 subjects). Patients were
randomized (1:1:1) into three groups with post-baseline liver
biopsy being performed at 24 weeks, 48 weeks, or 72 weeks,
respectively. In May 2022, the
Company concluded that the Open-Label part of the study met its
objective and discontinued the Open-Label part.
The second part, a randomized, double-blind, placebo-controlled
study, is designed to evaluate the safety and efficacy of Aramchol
Meglumine to support regulatory approval, with both a
histology-based phase and a clinically based phase. As currently
designed, a total of 2000 subjects with NASH and liver fibrosis
stage 2 and 3 who are overweight and are either pre-diabetic or
have type 2 diabetes are expected to be randomized 2:1 to receive
Aramchol Meglumine or matching placebo. In the histology-based
phase, we intend to treat 1000 subjects with Aramchol or matching
placebo for 72 weeks until the second biopsy. The histology-based
data is intended to serve as the basis for the submission of a
Sub-part H marketing authorization application under regulatory
provisions of accelerated/conditional approval.
Following the discontinuation of the Open-Label Part of the
ARMOR Study, the Company has no current plans to initiate the
Double-Blind part of the ARMOR Study, the commencement of which
depends on the outcome of its evaluation of strategic
alternatives.
About Galmed Pharmaceuticals Ltd.
Galmed Pharmaceuticals Ltd. is a clinical stage drug development
biopharmaceutical company for liver, metabolic and inflammatory
diseases. Their lead compound, Aramchol™, a backbone drug candidate
for the treatment of NASH and fibrosis is currently in a Phase 3
registrational study. Galmed is also collaborating with
the Hebrew University in the development of Amilo-5MER, a
5 amino acid synthetic peptide.
Forward-Looking Statements:
Forward-looking statements relate to anticipated or expected
events, activities, trends or results as of the date they are made.
Because forward-looking statements relate to matters that have not
yet occurred, these statements are inherently subject to risks and
uncertainties that could cause our actual results to differ
materially from any future results expressed or implied by the
forward-looking statements. Many factors could cause our actual
activities or results to differ materially from the activities and
results anticipated in forward-looking statements, including, but
not limited to, the timing and cost of our any pre-clinical or
clinical trial, for our product candidates;completion and receiving
favorable results of any pre-clinical or clinical trial;the impact
of the COVID-19 pandemic on our operations;regulatory action with
respect to Aramchol or any other product candidate by the U.S. Food
and Drug Administration, or the FDA, or the European Medicines
Authority, or EMA, including but not limited to acceptance of an
application for marketing authorization, review and approval of
such application, and, if approved, the scope of the approved
indication and labeling;the commercial launch and future sales of
Aramchol and any future product candidates;our ability to comply
with all applicable post-market regulatory requirements for
Aramchol or any other product candidate in the countries in which
we seek to market the product;our ability to achieve favorable
pricing for Aramchol or any other product candidate;our
expectations regarding the commercial market for non-alcoholic
steato-hepatitis, or NASH, in patients or any other targeted
indication;third-party payor reimbursement for Aramchol or any
other product candidate;our estimates regarding anticipated capital
requirements and our needs for additional financing;market adoption
of Aramchol or any other product candidate by physicians and
patients;the timing, cost or other aspects of the commercial launch
of Aramchol or any other product candidate;our ability to obtain
and maintain adequate protection of our intellectual property;the
possibility that we may face third-party claims of intellectual
property infringement;our ability to manufacture our product
candidates in commercial quantities, at an adequate quality or at
an acceptable cost;our ability to establish adequate sales,
marketing and distribution channels;intense competition in our
industry, with competitors having substantially greater financial,
technological, research and development, regulatory and clinical,
manufacturing, marketing and sales, distribution and personnel
resources than we do;the development and approval of the use of
Aramchol or any other product candidate for additional indications
or in combination therapy;our ability to maintain the listing of
our ordinary share on The Nasdaq Capital Market; andour
expectations regarding licensing, acquisitions and strategic
operations. We believe these forward-looking statements are
reasonable; however, these statements are only current predictions
and are subject to known and unknown risks, uncertainties and other
factors that may cause our or our industry's actual results, levels
of activity, performance or achievements to be materially different
from those anticipated by the forward-looking statements. We
discuss many of these risks in our Annual Report on Form 20-F for
the year ended December 31, 2021 filed with the SEC
on May 2, 2022 in greater detail under the heading "Risk
Factors" and elsewhere in the Annual Report, in our Reports on Form
6-K filed with the SEC on August 4,
2022 and November 16, 2022 and this press release.
Given these uncertainties, you should not rely upon forward-looking
statements as predictions of future events. All forward-looking
statements attributable to us or persons acting on our behalf speak
only as of the date hereof and are expressly qualified in their
entirety by the cautionary statements included in this report. We
undertake no obligations to update or revise forward-looking
statements to reflect events or circumstances that arise after the
date made or to reflect the occurrence of unanticipated events. In
evaluating forward-looking statements, you should consider these
risks and uncertainties.
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