STATEN
ISLAND, N.Y., May 2, 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) were presented at the 34th Congress
of ESCMID Global (European Society of Clinical Microbiology and
Infectious Diseases) on April
30th which was held in Barcelona, Spain, April
27-30, 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 gave 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 included
additional analyses of clinical and microbiological data from the
Phase 2b Segment of the trial.
In addition to Dr. Garey's oral presentation, Dr. Eugenie
Basseres, Research Scientist, University of
Houston College of Pharmacy presented a scientific poster
entitled: Antibacterial activity of ibezapolstat against
antimicrobial resistant clinical strains of Clostridioides
difficile. Dr. Garey summarized the significance of these data
presented and stated that: "These findings show that ibezapolstat's
unique mechanism of activity, inhibition of DNA polymerase IIIC,
translates into in vitro activity against C. difficile
strains with reduced susceptibility to fidaxomicin and vancomycin.
As antimicrobial-resistant strains continue to emerge in the
community, ibezapolstat will become a valuable therapeutic
option."
Commenting on his presentation, Dr. Garey stated: "This
randomized, active-controlled study showed ibezapolstat was
comparable to vancomycin in achieving clinical cure in patients
with mild-to-moderate CDI. Notably, no patients whose CDI was cured
by ibezapolstat experienced recurrence of their disease within the
28-day follow-up period. These data reinforce earlier findings
related to the anti-recurrence properties of ibezapolstat and
warrant further development in Phase 3 trials with further
microbiome studies planned to confirm the mechanisms behind these
clinical findings. He added that: "A new analysis from these
clinical results showed a time to resolution of diarrhea similar
vancomycin an important patient reported outcome."
The presentation and poster are available on the Acurx
Pharmaceuticals website following their respective presentations at
the conference. www.acurxpharma.com
The complete Phase 2 results are being prepared for submission
to a prominent scientific journal.
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.
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.