- Additional analyses of clinical and microbiological data
from the Phase 2b segment show
favorable gut microbiome changes including increased relative
proportion of Actinobacteria in ibezapolstat-treated
patients with C. difficile Infection (CDI)
- Results consistent with those shown in earlier human
volunteer studies and Phase 2a studies
- Preservation and increased concentrations of beneficial
Firmicute (Bacilotta) phylum known to be involved in bile acid
homeostasis and short chain fatty acid metabolism was
demonstrated
- Actinobacteria and Bacteroides preservation also confirmed
using quantitative analysis
STATEN
ISLAND, N.Y., July 15,
2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP)
a clinical stage biopharmaceutical company
developing a new class of antibiotics for difficult-to-treat
bacterial infections, announced today that results from the
ibezapolstat (IBZ) Phase 2 clinical trial in patients with C.
difficile Infection (CDI) were presented at the 17th Biennial
Congress of the Anaerobe Society of the Americas on July 11th which was held at the University of Michigan, Ann Arbor, from
July 8 to 11, 2024. Taryn A.
Eubank, PharmD, BCIDP, Research Assistant Professor, University of Houston College of Pharmacy delivered
an oral presentation entitled: "Clinical Efficacy of Ibezapolstat
in CDI: Results from Phase 2 trials."
Commenting on Dr. Eubank's presentation, 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, stated:
"The ibezapolstat clinical development plan has included the
most robust microbiome development plan ever undertaken with prior
analyses predicting an anti-recurrence effect of ibezapolstat in
patients with CDI." Dr. Garey further added: "Microbiome results
from the Phase 2b trial are helping
to validate this approach as a consistent anti-recurrence effect
has been seen along with the microbiome effect explaining the
underlying mechanism of action. I would anticipate that these
analyses will set a new standard for CDI-directed antibiotics and
perhaps for antibiotic development, in general."
Robert J. DeLuccia, Executive Chairman of Acurx, stated:
"Ibezapolstat continues to demonstrate favorable effects on the gut
microbiome while at the same time curing the C. difficile
bacterial infection comparable to standard of care
antibiotics. As we continue to prepare for initiation of our
Phase 3 clinical program, we expect this feature of ibezapolstat's
dual mechanism of action to be an important competitive advantage
by reducing the recurrence of the infection, as well as improving
the health of the gut microbiome."
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 now preparing to submit requests for guidance
to initiate clinical trials in the European Union, the United Kingdom, Japan and Canada.
About the Anaerobe Society of the Americas
Founded in 1992, The Anaerobe Society of the Americas is an
international organization, promoting the study and application of
knowledge of anaerobic bacteriology. The primary activity of the
society is organizing the biennial Anaerobe Congress for
researchers, clinicians, and laboratory scientists from around the
world to engage in presentations, exchanges, and dialogues related
to anaerobes.
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 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.