- Ibezapolstat outperformed vancomycin showing eradication of
fecal C. difficile at Day 3 of treatment in 15 of 16 treated
patients (94%), versus vancomycin which had eradication of C.
difficile in 10 of 14 treated patients (71%).
- Ibezapolstat, but not vancomycin, consistently preserved and
allowed regrowth of key gut bacterial species believed to confer
health benefits including to prevent recurrence of CDI
- Further analyses will be forthcoming Q1 2024, as data become
available, regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC)
data up to 94 days
- Preparation underway for meetings with FDA, European Medicines
Agency and other global regulatory agencies and advancement to
international Phase 3 clinical trials
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation
STATEN
ISLAND, N.Y., Jan. 17,
2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage
biopharmaceutical company developing a new class of small molecule
antibiotics for difficult-to-treat bacterial infections,
today announced positive comparative microbiology and
microbiome data for ibezapolstat, its lead antibiotic candidate,
from the Company's recently completed Phase 2b clinical trial in patients with CDI.
Data showed that ibezapolstat outperformed vancomycin, a standard
of care to treat patients with CDI, with eradication of fecal C.
difficile at Day 3 of treatment in 15 of 16 patients (94%)
versus vancomycin which had eradication of fecal C.
difficile in 10 of 14 patients (71%). In addition,
ibezapolstat, but not vancomycin, consistently preserved and
allowed regrowth of key gut bacterial species believed to confer
health benefits including to prevent CDI recurrence. Further
analyses will be forthcoming Q1 2024, as data become available,
regarding other endpoints from the Phase 2b trial, including Extended Clinical Cure (ECC)
data up to 94 days. Preparation is underway for meetings with
FDA, European Medicines Agency and other global regulatory agencies
and advancement to international Phase 3 clinical trials.
The Company also announced that a scientific poster will be
presented on January 18, 2023 at the
Gulf Coast Consortia Antimicrobial Resistance (AMR) Conference in
Houston, Texas by Kevin Garey, PharmD, MS, Professor and Chair,
University of Houston College of
Pharmacy, the Principal Investigator for microbiology and
microbiome aspects of the ibezapolstat clinical trial program and
Acurx Scientific Advisory Board member. The poster will show
comparative data details from the Phase 2b clinical trial entitled: "A Phase 2,
Randomized, Double-Blind Study of Ibezapolstat Compared with
Vancomycin for the Treatment of Clostridioides difficile
Infection."
After the presentation, the poster will be posted on Acurx
website: www.acurxpharma.com
According to Dr. Garey: "These results help validate our ongoing
scientific investigations into the anti-CDI recurrence effects of
ibezapolstat. Our microbiologic findings show that markedly fewer
patients treated with ibezapolstat had persistent C.
difficile compared to patients treated with vancomycin. He
further stated: "Preservation of key health-conferring native gut
bacteria, such as Firmicutes, in patients treated with ibezapolstat
has now been shown consistently during all clinical studies. These
results correlate with prior findings by showing superior
preservation of key native gut bacteria compared to vancomycin in
CDI patients. Preservation of native gut bacteria during treatment
for CDI is believed to be a key component for preventing recurrence
of CDI. These findings will need to be further validated in the
phase 3 studies but the results to date support the importance of
this new class of antibiotics with a novel mechanism of action that
does not target native gut bacteria."
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "These new comparative data are very
important and timely to enhance our data package for an end of
Phase 2 FDA Meeting which is targeted for second quarter this year.
He further stated: "Parallel preparations continue on schedule for
Phase 3 clinical trials start up later this year, including timely
availability of clinical trial supply.
David P. Luci, President &
CEO of Acurx, stated: "Ibezapolstat continues to demonstrate
success compared to a standard of care, oral vancomycin, to treat
patients with CDI. We anticipate that favorable differentiation
between the two therapeutic options will continue to be shown in Q1
2024 including extended clinical cure and additional microbiome
comparison data. We expect to leverage this success in a
$1 billion plus US CDI global market
as we move forward with an international Phase 3 clinical trial
mandate." He added: "The Company also anticipates its price point
for ibezapolstat, if approved, could meet or beat other antibiotics
recommended for use in treating patients with CDI, thereby
providing the whole package of clinical comparability with
microbiome health, safety and cost for patients with this
life-threatening disease."
About the Ibezapolstat Phase
2 Clinical Trial
The completed multicenter,
open-label single-arm segment (Phase 2a) study was
followed by a double-blind, randomized, active-controlled, non-inferiority, segment
(Phase 2b) at 28 US clinical
trial sites which together comprise the Phase 2 clinical trial.
(see https://clinicaltrials.gov/ct2/show/NCT04247542). This
Phase 2 clinical trial was designed to
evaluate the clinical efficacy of ibezapolstat in the treatment of
CDI including
pharmacokinetics and microbiome changes from baseline
and continue to test for anti- recurrence
microbiome properties seen in the Phase 2a trial, including the
treatment- related changes in alpha diversity and bacterial
abundance and effects on bile acid metabolism.
The completed Phase 2a segment of this trial was an open label
cohort of up to 20 subjects from study centers in the United States. In this cohort, 10 patients
with diarrhea caused by C. difficile were treated
with ibezapolstat 450 mg orally, twice daily for 10 days. All
patients were followed for recurrence for 28± 2 days. Per protocol,
after 10 patients of the projected 20 Phase 2a patients completed
treatment (100% cured infection at End of Treatment), the Trial
Oversight Committee assessed the safety and tolerability and made
its recommendation regarding early termination of the Phase 2a
study and advancement to the Ph2b segment. The Company's Scientific
Advisory Board concurred with this recommendation.
In the now completed Phase 2b
trial segment, 32 patients with CDI were enrolled and randomized in
a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or
vancomycin 125 mg orally every 6 hours, in each case, for 10 days
and followed for 28 ± 2 days following the end of treatment for
recurrence of CDI. The two treatments were identical in appearance,
dosing times, and number of capsules administered to maintain the
blind. The overall observed Clinical Cure rate in the combined
Phase 2 trials in patients with CDI was 96% (25 out of 26
patients), based on 10 out of 10 patients (100%) in Phase 2a in the
Modified Intent to Treat Population, plus 15 out of 16 (94%)
patients in Phase 2b in the Per
Protocol Population, who experienced Clinical Cure during treatment
with ibezapolstat. Ibezapolstat was well-tolerated, with three
patients each experiencing one mild adverse event assessed by the
blinded investigator to be drug-related. All three events were
gastrointestinal in nature and resolved without treatment. There
were no drug-related treatment withdrawals or no drug-related
serious adverse events, or other safety findings of concern. In the
Phase 2b vancomycin control arm, 14
out of 14 patients experienced Clinical Cure. The Company is
confident that based on the pooled Phase 2 ibezapolstat Clinical
Cure rate of 96% and the historical vancomycin cure rate of
approximately 81% (Vancocin® Prescribing Information, January 2021), we will demonstrate
non-inferiority of ibezapolstat to vancomycin in Phase 3 trials in
accordance with the applicable FDA Guidance for Industry (October,
2022).
The Phase 2b clinical trial
segment was discontinued due to success. The Company made this
decision in consultation with its medical and scientific advisors
and statisticians based on observed aggregate blinded data and
other factors, including the cost to maintain clinical trial sites
and slow enrollment due to COVID-19 and its aftermath. The Company
had determined that the trial performed as anticipated for both
treatments, ibezapolstat and the control antibiotic vancomycin (a
standard of care to treat patients with CDI), with high rates of
clinical cure observed across the trial without any emerging safety
concerns. Accordingly, an Independent Data Monitoring Committee was
not required to perform an interim analysis of this Phase
2b trial data as originally planned.
The Company anticipated that this decision would allow the Company
to advance this first-in-class, FDA QIDP/Fast Track-designated
antibiotic product candidate to Phase 3 clinical trials more
expeditiously.
The Phase 2b trial was originally
designed to be a non-inferiority (NI) trial and later amended to
include an interim efficacy analysis with review by an Independent
Data Monitoring Committee (IDMC). The decision to end the trial
early based on blinded clinical observations obviated the need for
an interim analysis, IDMC review, and NI assessment. The Company
determined, in consultation with its clinical and statistical
experts, that presenting clinical cure rates for the primary
efficacy endpoint is the most appropriate representation for the
clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate
pharmacokinetics (PK) and microbiome changes and test for
anti-recurrence microbiome properties, including the change from
baseline in alpha diversity and bacterial abundance, especially
overgrowth of healthy gut microbiota Actinobacteria and
Firmicute phylum species during and after therapy. Phase 2a data
demonstrated complete eradication of colonic C.
difficile by day three of treatment with ibezapolstat as
well as the observed overgrowth of healthy gut microbiota,
Actinobacteria and Firmicute phyla species, during and after
therapy. Very importantly, emerging data show an increased
concentration of secondary bile acids during and following
ibezapolstat therapy which is known to correlate with colonization
resistance against C. difficile. A decrease in
primary bile acids and the favorable increase in the ratio of
secondary-to-primary bile acids suggest that ibezapolstat may
reduce the likelihood of CDI recurrence when compared to
vancomycin.
About Ibezapolstat
Ibezapolstat is a novel, orally administered antibiotic being
developed as a Gram-Positive Selective Spectrum (GPSS™)
antibacterial. It is the first of a new class of DNA polymerase
IIIC inhibitors under development by Acurx to treat bacterial
infections. Ibezapolstat's unique spectrum of activity, which
includes C. difficile but spares other Firmicutes and the important
Actinobacteria phyla, appears to contribute to the maintenance of a
healthy gut microbiome.
In June 2018, ibezapolstat was
designated by the U.S. Food and Drug Administration (FDA) as a
Qualified Infectious Disease Product (QIDP) for the treatment of
patients with CDI and will be eligible to benefit from the
incentives for the development of new antibiotics established under
the Generating New Antibiotic Incentives Now (GAIN) Act. In
January 2019, FDA granted "Fast
Track" designation to ibezapolstat for the treatment
of patients with CDI. The CDC has designated C.
difficile as an urgent threat highlighting the need for
new antibiotics to treat CDI.
About Clostridioides difficile Infection
(CDI). According to the 2017 Update (published February 2018) of the Clinical Practice
Guidelines for C. difficile Infection by the Infectious Diseases
Society of America (IDSA) and Society or Healthcare Epidemiology of
America (SHEA), CDI remains
a significant medical
problem in hospitals, in long-term care facilities
and in the community. C. difficile is one of the most
common causes of health care- associated infections in U.S.
hospitals (Lessa, et al, 2015, New England Journal of
Medicine). Recent estimates suggest
C. difficile approaches 500,000
infections annually in the U.S. and is associated with
approximately 20,000 deaths annually. (Guh, 2020, New England
Journal of Medicine). Based on internal estimates, the recurrence
rate for the antibiotics currently used to treat CDI is between 20%
and 40% among approximately 150,000 patients treated. We believe
the annual incidence of CDI in the U.S. approaches 600,000
infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI)
and Bile Acid Metabolism
C. difficile can be a
normal component of the healthy gut microbiome, but when the
microbiome is thrown out of balance, the C.
difficile can thrive and cause an infection. After
colonization with C. difficile, the organism
produces and releases the main virulence factors, the two
large clostridial toxins A (TcdA) and B (TcdB).
(Kachrimanidou, Microorganisms 2020, 8, 200;
doi:10.3390/microorganisms8020200.) TcdA and TcdB are exotoxins that bind
to human intestinal epithelial cells and are responsible for
inflammation, fluid and mucous secretion, as well as damage to the
intestinal mucosa.
Bile acids perform many functional roles
in the GI tract, with one of the most important being
maintenance of a healthy microbiome by inhibiting C.
difficile growth. Primary bile acids, which are secreted
by the liver into the intestines, promote germination of C.
difficile spores and thereby increase the risk of
recurrent CDI after successful treatment of an initial episode. On
the other hand, secondary bile acids, which are produced by normal
gut microbiota through metabolism of primary bile acids, do not
induce C. difficile sporulation and therefore protect
against recurrent disease. Since ibezapolstat treatment leads to
minimal disruption of the gut microbiome, bacterial production of
secondary bile acids continues which may contribute to an
anti-recurrence effect. Beneficial effects of bile acids
include a decrease
in primary bile acids and an increase
in secondary bile acids in patients with
CDI, which was observed in the Company's Ph2a trial results and
previously reported (CID, 2022).
About Acurx Pharmaceuticals, Inc.
Acurx
Pharmaceuticals is a late-stage biopharmaceutical company focused
on developing a new class of small molecule antibiotics for
difficult-to-treat bacterial infections. The Company's approach is
to develop antibiotic candidates with a Gram-positive selective
spectrum (GPSS®) that blocks the active site of the Gram+ specific
bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA
replication and leading to Gram-positive bacterial cell death. Its
R&D pipeline includes antibiotic product candidates that target
Gram-positive bacteria, including Clostridioides difficile,
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin
resistant Enterococcus (VRE) and drug-resistant Streptococcus
pneumoniae (DRSP).
To learn more about
Acurx Pharmaceuticals and its product
pipeline, please visit www.acurxpharma.com
Forward-Looking Statements
Any statements in this
press release about our future expectations, plans and prospects,
including statements regarding our strategy, future operations,
prospects, plans and objectives, and other statements containing
the words "believes," "anticipates," "plans," "expects," 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: whether ibezapolstat will benefit from the QIDP
designation; whether ibezapolstat will advance through the clinical
trial process on a timely basis; whether the results of the
clinical trials of ibezapolstat will warrant the submission of
applications for marketing approval, and if so, whether
ibezapolstat will receive approval from the FDA or equivalent
foreign regulatory agencies where approval is sought; whether, if
ibezapolstat obtains approval, it will be successfully distributed
and marketed; and other risks and uncertainties described in the
Company's annual report filed with the Securities and Exchange
Commission on Form 10-K for the year ended December 31, 2022, and in the Company's
subsequent filings with the Securities and Exchange Commission.
Such forward- looking statements speak only as of the date of this
press release, and Acurx disclaims any intent or obligation to
update these forward-looking statements to reflect events or
circumstances after the date of such statements, except as may be
required by law.
Investor Contact: Acurx
Pharmaceuticals, Inc.
David P. Luci,
President &
CEO
Tel: 917-533 1469
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.