STATEN ISLAND, N.Y.,
April 25,
2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a clinical stage
biopharmaceutical company developing a new class of antibiotics for
difficult-to-treat bacterial infections, announced today that
results from the ibezapolstat Phase 2 clinical trial in patients
with C. difficile Infection (CDI) will be presented at the
34th Congress of ESCMID Global (European Society of
Clinical Microbiology and Infectious Diseases) being held in
Barcelona, Spain, April 27-30, 2024.
Kevin Garey, PharmD, FIDSA, MS,
Professor and Chair, University of
Houston College of Pharmacy, and the Principal Investigator
for microbiology and microbiome aspects of the ibezapolstat
clinical trial program and Acurx Scientific Advisory Board member
will give an oral presentation entitled: A Phase 2, Randomized,
Double-Blind Study of Ibezapolstat Compared with Vancomycin for the
Treatment of Clostridioides difficile Infection. The
presentation will include additional analyses of clinical and
microbiological data.
Oral Presentation:
Tuesday, April 30, 2024: 8:30am
Title: Efficacy and safety of ibezapolstat compared with
vancomycin for the treatment of Clostridioides difficile infection
- a phase 2, randomized, double-blind study
Presenter:
Kevin Garey, PharmD, FIDSA'
Professor and Chair, University of
Houston College of Pharmacy
Location: Hall H
Poster Presentation:
Sunday, April 28, 2024; 12:00pm
Poster Title: Antibacterial activity of ibezapolstat against
antimicrobial resistant clinical strains of Clostridioides
difficile
Presenter: Eugenie Dr. Eugenie
Basseres, Research Scientist, University of Houston College of Pharmacy
Location: Poster #P2327
The presentation and poster will be made available on the Acurx
Pharmaceuticals website following their respective presentations at
the conference. www.acurxpharma.com
About ESCMID Global (formerly ECCMID)
ESCMID (European
Society of Clinical Microbiology and Infectious Diseases) Global
conference is recognized as the largest international forum for
presentations and discussions of research in the fields of clinical
microbiology and infection for experts from academia, the clinical
setting and the industry. ESCMID's yearly congress attracts over
14,000 participants. ECCMID offers a wide range of sessions
including: keynotes, symposia, poster sessions, educational
workshops, meet-the-expert sessions and more. The society's
executive power is vested in ESCMID in Executive Committee elected
by the ESCMID members. The administrative ESCMID office is in
Basel, Switzerland.
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 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 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. 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.