STATEN ISLAND,
N.Y., Dec. 6,
2021 /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
first patient has been enrolled in its Phase 2b clinical trial of ibezapolstat, its lead
antibiotic candidate, against the standard of care to treat CDI,
vancomycin, in a 64 patient double-blind randomized trial expected
to be completed mid-2022. C. difficile bacteria
remains on the Centers for Disease Control and Prevention (CDC)
Urgent Threat list, highlighting the need for new therapeutics to
treat CDI. Ibezapolstat is FDA QIDP and Fast Track Designated for
priority review.
Robert J. DeLuccia, Executive
Chairman of Acurx, stated, "With the excellent clinical results and
very good safety and tolerability demonstrated in the Phase 2a
segment of this ongoing trial, we validated the bacterial pol IIIC
enzyme as a therapeutic target for ibezapolstat, our first product
candidate in our new class of antibiotics. Additionally, this trial
segment showed potentially beneficial effects of ibezapolstat on
the intestinal microbiome and bile acid metabolism." He further
stated that "Initiating this Phase 2b
segment is a very important clinical development milestone for our
company. We look forward to successfully completing enrollment in
mid-2022."
About the Ibezapolstat Phase 2 Clinical Trial. The
completed multicenter, open-label single-arm segment (Phase 2a)
study is now followed by this double-blind, randomized,
active-controlled, non-inferiority, segment (Phase 2b) at 12 US clinical trial sites which together
comprise the Phase 2 clinical trial (see
https://clinicaltrials.gov/ct2/show/NCT04247542). This Phase 2
clinical trial is 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,
the Trial Oversight Committee assessed the safety and tolerability
and made its recommendation regarding early termination of the
Phase 2a study. Based on the recommendation of Acurx's Scientific
Advisory Board (SAB) and Trial Oversight Committee, we terminated
enrollment in Phase 2a early and are now advancing to Phase
2b. The SAB unanimously supported the
early termination of the Phase 2a trial after 10 patients were
enrolled in the trial instead of 20 patients as originally planned.
The early termination was based on the evidence of meeting the
primary and secondary endpoints of eliminating the infection
(100%), with no recurrences of infection (100%), and with an
acceptable adverse event profile. In the upcoming Phase
2b, approximately 64 additional
patients with CDI will be 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 will be 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 continue to 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 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 of two of the three
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 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.
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 United States 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 factors.
In addition, the forward-looking statements included in this press
release represent our views as of December
6, 2021. We anticipate that subsequent events and
developments will cause our views to change. However, while we may
elect to update these forward-looking statements at some point in
the future, we specifically disclaim any obligation to do so.
Investor Contact: Acurx Pharmaceuticals, Inc.
David P. Luci, President & CEO
Tel: 917-533-1469
Email: davidluci@acurxpharma.com
View original
content:https://www.prnewswire.com/news-releases/acurx-announces-first-patient-enrolled-in-phase-2b-clinical-trial-of-its-lead-antibiotic-for-treatment-of-clostridioides-difficile-infection-cdi-301437539.html
SOURCE Acurx Pharmaceuticals, Inc.