STATEN
ISLAND, N.Y., July 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 that a new patent has been granted by the United
States Patent and Trademark Office (USPTO) on July 16, 2024. This patent relates to
ibezapolstat and its use to treat
C. difficile Infection (CDI) while reducing the
recurrence of the infection, as well as improving the health of the
gut microbiome. This is the latest in the series of granted patents
and pending patent applications that Acrux has filed to protect its
proprietary technologies in the field of antimicrobials.
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "This patent is very important and
timely as ibezapolstat continues to demonstrate previously
unexpected and favorable effects on the gut microbiome while at the
same time curing the C. difficile bacterial infection and
preventing recurrent infection." He further added: "As we continue
to prepare for initiation of our Phase 3 clinical program, we
expect this feature of ibezapolstat's selective mechanism of action
to be further demonstrated and to be an important competitive
advantage over currently available antibiotics by reducing the
recurrence of the infection. This could have a dramatically
favorable effect on patient outcomes and on reducing downstream
healthcare costs."
David P. Luci, President &
CEO of Acurx stated: "This latest patent is part of our company's
pivotal product, ibezapolstat, which is a two-dimensional
antibiotic to cure infections clinically comparable to marketed
antibiotics while restoring the microbiome and preventing
reinfections which is unusually positive for CDI antibiotics."
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 now preparing to submit requests for guidance
to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.
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.
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.
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 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).
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.
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. 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
healthcare-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.