- Based on observed aggregate blinded data the Company has
determined that both treatments, ibezapolstat and the control
antibiotic vancomycin, have performed as expected
- High rates of Clinical Cure were observed without any
emerging safety concerns
- Data will be analyzed and topline efficacy results will
be reported as soon as possible
- This successful milestone will allow advancement of this
first-in-class, FDA QIDP/Fast Track-designated
antibiotic candidate to Phase 3 clinical trials more
expeditiously
STATEN
ISLAND, N.Y., Oct. 2, 2023
/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 the Company has
discontinued the Phase 2b clinical
trial of its lead antibiotic candidate, ibezapolstat, for the
treatment of patients with Clostridioides difficile
infection (CDI) 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. The Company has
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, the Independent Data Monitoring Committee will not
be required to perform an interim analysis of this Phase
2b trial data as originally planned
and the Company has discontinued the trial. Acurx will analyze the
data and report topline efficacy results promptly. The Company
anticipates that this decision will allow the Company to advance
this first-in-class, FDA QIDP/Fast Track-designated antibiotic
product candidate to Phase 3 clinical trials more
expeditiously.
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "Considering the totality and weight of
evidence of our preclinical, Phase 1 and Phase 2a clinical results
and now with the observed aggregate blinded data, we
determined it was in the best interests of the Company and its
shareholders to discontinue the Phase 2b clinical trial early and prepare for Phase 3
clinical trials. Mr. DeLuccia stated further, "We look
forward to compiling, analyzing the data and reporting topline
results for the study's primary clinical endpoint and safety
aspects as soon as possible". He further stated: "We thank the
clinical trial investigators and patients across the country who
participated in this study allowing advancement of this promising
new antibiotic into late-stage clinical trials for this serious and
life-threating infection which is classified by FDA and CDC as an
urgent priority for which new classes of antibiotics are
needed."
David P. Luci, the Company's
President and Chief Executive Officer, stated: "We also look
forward to reporting the full ibezapolstat data which will include
the most extensive data for any antibiotic on sustained clinical
cure to date in patients with CDI, as well as a comparison of the
effect on the microbiome between oral ibezapolstat and oral
vancomycin. We believe that, if approved by FDA for marketing,
these attributes will support the use of ibezapolstat for
front-line treatment of CDI."
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. In the now discontinued 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. This Phase 2
clinical trial 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. In the event non-inferiority of ibezapolstat to
vancomycin is demonstrated, further analysis will be conducted to
test for superiority.
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
About the Microbiome in Clostridioides
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.
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
for 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 of two
of thethree antibiotics currently used to treat CDI is
between 20% and 40% among
approximately150,000 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 Acurx Pharmaceuticals, Inc.
Acurx
Pharmaceuticals is a clinical stage biopharmaceutical company
focused on developing new antibiotics for difficult to treat
infections. The Company's approach is to develop antibiotic
candidates that target the DNA polymerase IIIC enzyme, and its
R&D pipeline includes early-stage 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 Qualified Infectious
Disease Product 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 U.S. Food and Drug
Administration 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 filings with the
Securities and Exchange Commission ("SEC"), including the factors
described in the section entitled "Risk Factors" in the Company's
Annual Report on Form 10-K for the year ended December 31, 2022, and in other filings that the
Company has made and future filings the Company will make with the
SEC. The Company expressly disclaims any obligation or undertaking
to release publicly any updates or revisions to any forward-looking
statements contained herein to reflect any change in its
expectations with regard thereto or any change in events,
conditions, or circumstances on which any such statements are
based.
Investor Contact:
Acurx Pharmaceuticals, Inc.
David P. Luci, President & Chief Executive Officer
Tel: 917-533-1469
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.