- The data presented indicate a favorable gut bile acid
profile which may contribute to ibezapostat's beneficial
anti-recurrence effect in patients with C. difficile Infection
(CDI)
- Ibezapolstat treatment of patients with CDI is associated
with the restoration of beneficial bacterial classes in the
gut
- 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 to be followed by
the United Kingdom, Japan and Canada
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation from FDA
STATEN
ISLAND, N.Y., Oct. 21,
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 the presentation of a scientific poster at the
Infectious Diseases Society of America (IDSA) IDWeek™ 2024
Conference held October 16-19, 2024
in Los Angeles, CA.
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, and
Taryn A. Eubank, PharmD, BCIDP,
Research Assistant Professor, University of
Houston College of Pharmacy presented a scientific poster
entitled: A phase 2, randomized double-blind study of
ibezapolstat compared with vancomycin for the treatment of C.
difficile infection: clinical and microbiome evaluation.
In the Phase 2b clinical trial,
ibezapolstat had comparable clinical cure and sustained clinical
cure rates and safety profile to vancomycin. Also, 5 of 5
ibezapolstat patients who were followed for 3 months after end of
treatment (EOT) experienced no recurrence. Favorable microbiome
results were observed in ibezapolsat-treated patients who had
increased proportion of Actinobacteriota and beneficial
Bacillota. Furthermore, ibezapolstat-treated patients showed
decreased concentrations of fecal primary bile acids, and higher
ratios of secondary to primary bile acids than vancomycin-treated
patients.
According to Dr. Garey: "These exciting results demonstrate two
properties of ibezapolstat which may contribute to the
anti-recurrence effect. First, the preservation and restoration of
beneficial bacterial classes in the gut provide resistance to
recolonization by C. difficile. Second, these data,
presented for the first time, indicate that these beneficial
bacteria known to metabolize primary to secondary bile acids
persist in ibezapolstat-treated patients providing another
important mechanism to prevent recurrent CDI".
Robert J. DeLuccia, Executive Chairman of Acurx, stated:
"This new impressive bile acid and microbiome data compliment and
extend our knowledge of ibezapolstat's pharmacologic profile.
These results, when added to previous work showing anti-virulence
properties, preclinically, give us a high level of confidence that
our excellent Phase 2 clinical results will be confirmed in our
Phase 3 studies". The scientific poster is available on the
Acurx Pharmaceuticals website at 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, to be followed by requests to be submitted
in 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 IDSA and
IDWeek
The Infectious Diseases Society of America
(IDSA) is a community of over 12,000 physicians, scientists
and public health experts who specialize in infectious diseases.
Our mission is to improve the health of individuals, communities,
and society by promoting excellence in patient care, education,
research, public health, and prevention relating to infectious
diseases. IDWeek is the joint annual meeting of the
Infectious Diseases Society of America (IDSA), Society for
Healthcare Epidemiology of America (SHEA), the HIV Medicine
Association (HIVMA), the Pediatric Infectious Diseases Society
(PIDS), and the Society of Infectious Diseases Pharmacists
(SIDP).
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
the Phase 2a trial segment, 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 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 (both trial segments), 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.