- New analyses extend data on beneficial effects of
ibezapolstat on the gut microbiome
- Confirmed ibezapolstat's favorable pharmacokinetics showing
low systemic exposure and high colonic concentrations
- Selected ACX-375 analogues demonstrated in vitro activity
against Anthrax (B. anthracis), a Bioterrorism Category A pathogen,
including activity against ciprofloxacin resistant Anthrax.
Planning is underway for an Anthrax bioterrorism development
program
- Preparation continues to advance ibezapolstat into
international Phase 3 clinical trials for treatment of C. difficile
Infection (CDI)
- Preparing to submit requests for regulatory guidance to
initiate clinical trials in the European Union, the United Kingdom, Japan and Canada
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation from FDA
STATEN
ISLAND, N.Y., Sept. 26,
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 results from new analyses that extend data on the
beneficial effects of ibezapolstat on the gut microbiome. The data
show an increased proportion of Actinobacteriota and increased
quantity of beneficial Bacillota (Firmicutes) leading to reversal
of dysbiosis and contributing to the CDI anti-recurrence effect of
ibezapolstat.
Additionally, ibezapolstat's favorable pharmacokinetics
properties were confirmed showing mean systemic exposure below
1mcg/mL and fecal concentrations well in excess of the minimal
inhibitory concentration (MIC) for C. difficile.
Microbiological testing of certain ACX-375 DNA pol IIIC
analogues in independent qualified laboratories, including the
University of Florida, demonstrated in
vitro activity with MICs of 0.5-2mcg/mL against B.
anthracis (Anthrax), a Bioterrorism Category A pathogen,
including activity against ciprofloxacin resistant B.
anthracis.
The above results were presented at the premier International C.
difficile Symposium (ICDS) held in Bled, Slovenia on September
17-19, 2024. Kevin Garey,
PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy,
Principal Investigator for microbiology and microbiome aspects of
the ibezapolstat clinical trial program, and Acurx Scientific
Advisory Board member delivered a presentation entitled:
Ibezapolstat Preserves Key Clostridium leptum Species.
Microbiome Results from the Phase 2, Randomized, Double-blind Study
of ibezapolstat Compared with Vancomycin for the Treatment of
Clostridioides Difficile Infection.
According to Dr. Garey: "The microbiome data also show an
unexpected finding of a unique microbiome signature in two
vancomycin-treated patients in the Ph2b trial who experienced
recurrence of CDI. Since these changes were evident and observed
early during treatment and then consistently until the end of
therapy, they may be predictive of pending CDI recurrence and
suggest the need to modify therapy."
Robert J. DeLuccia, Executive Chairman of Acurx, stated:
"These new data add to and reinforce ibezapolstat's
emerging overall distinctive product profile, particularly the
favorable microbiome-related unexpected findings." He added:
"Furthermore, the initial in vitro activity shown against the
Bioterrorism Category A pathogen B. anthracis (Anthrax)
with some of our earlier-stage compounds included a
ciprofloxacin-resistant strain. Selective microbiome effects will
be tested with these new compounds as they proceed through
development to treat infections caused by methicillin-resistant
Staphylococcus aureus (MRSA) and other critical
gram-positive pathogens in parallel with planning for the Anthrax
bioterrorism program. The presentation is available on the
Acurx Pharmaceuticals website www.acurxpharma.com
Acurx has previously announced that it had a successful FDA
End-of-Phase 2 Meeting and Phase 3 Readiness for ibezapolstat for
the Treatment of C. difficile Infection. Agreement
with FDA was reached on key elements to move forward with its
international Phase 3 clinical trial program. Agreement was also
reached with FDA on the complete non-clinical and clinical
development plan for filing of a New Drug Application (NDA) for
marketing approval. Planning continues to advance ibezapolstat into
international Phase 3 clinical trials for treatment of C.
difficile Infection (CDI). Acurx is also preparing to submit
requests for regulatory guidance to initiate clinical trials in the
European Union, the United
Kingdom, Japan and
Canada.
Key elements for the two Phase 3, non-inferiority, pivotal
trials were confirmed and included agreement on the protocol
design, patient population, primary and secondary endpoints, and
size of the registration safety database. Based on FDA
recommendations, and in anticipation of an EMA Scientific Advice
Meeting, the primary efficacy analysis will be performed using a
Modified Intent-To-Treat (mITT) population consistent with EMA
requirements. This will result in an estimated 450 subjects in the
mITT population, randomized in a 1:1 ratio to either ibezapolstat
or standard-of-care vancomycin, enrolled into the initial Phase 3
trial. The trial design not only allows determination of
ibezapolstat's ability to achieve Clinical Cure of CDI as measured
2 days after 10 days of oral treatment, but also includes
assessment of ibezapolstat's potential effect on reduction of CDI
recurrence in the target population. In the event non-inferiority
of ibezapolstat to vancomycin is demonstrated, further analysis
will be conducted to test for superiority.
About the C. difficile Symposium (ICDS)
The International C. difficile Symposium (ICDS) is now
established as the premier venue for the review of Clostridium
difficile research.
The 1st meeting was held in Kranjska
Gora in 2004, the 2nd in Maribor in 2007, while all earlier
meetings were in Bled in 2010, 2012, 2015 and in 2018. ICDS in 2020
was held virtually. The 2024 meeting will provide the ideal
opportunity to review progress in epidemiology, diagnostics,
clinical trials, basic research and in understanding C.
difficile pathogenesis and controlling the devastating
disease it causes.
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. 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).
In the now completed Phase 2b
trial segment, which was discontinued due to success, 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 Company
previously reported that 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).
In the Phase 2 clinical trial, the Company also evaluated
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. The company also recently reported positive
extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead
antibiotic candidate, from the Company's recently completed Phase
2b clinical trial in patients with
CDI. This exploratory endpoint showed that 12 patients who agreed
to be followed up to three months following Clinical Cure of their
infection, 5 of 5 IBZ patients experienced no recurrence of
infection. In the vancomycin control arm of the trial, 7 of 7
patients experienced no recurrence of infection. ECC success is
defined as a clinical cure at the TOC visit (i.e., at least 48
hours post EOT) and no recurrence of CDI within the 56 ± 2 days
post EOT (ECC56) and 84 ± 2 days post EOT (ECC84) in patients who
consented to extended observation. In the Phase 2b trial, 100% (5 of 5) of ibezapolstat-treated
patients who agreed to observation for up to three months following
Clinical Cure of CDI experienced no recurrence of infection.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate planning
to advance to international Phase 3 clinical trials to treat
patients with C. difficile Infection (CDI). 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-positive
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,
2023, 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.