- In a total of 26 ibezapolstat-treated patients in Phases
2a and 2b, the Clinical Cure rate is
96%
- Meets protocol primary objective of assessing the primary
efficacy endpoint of the Clinical Cure rate after 10 days of
oral treatment
- Ibezapolstat was well tolerated; no drug-related Serious
Adverse Events
- Further analyses forthcoming regarding secondary and
exploratory endpoints, including Sustained Clinical Cure data,
Extended Clinical Cure data up to 94 days and comparative effects
on gut microbiome
- Preparation underway for End-of-Phase 2 FDA Meeting and
advancement to Phase 3
- Ibezapolstat has previously received FDA Qualified Infectious
Disease Product and Fast-Track Designation
Management will be available for Q&A on November 14, 2023 earnings call
https://www.acurxpharma.com/news-media/press-releases/detail/65/acurx-pharmaceuticals-to-discuss-third-quarter-2023
STATEN
ISLAND, N.Y., Nov. 2, 2023
/PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx"
or the "Company"), a clinical stage biopharmaceutical company
developing a new class of small molecule antibiotics for
difficult-to-treat bacterial infections, today announced efficacy
results from the Phase 2 clinical trial (Phase 2a segment and Phase
2b segment) of ibezapolstat for the
treatment of C. difficile Infection (CDI).
The Company previously announced that it decided to terminate
the Phase 2b vancomycin-controlled
trial segment early based on aggregate blinded data showing a high
observed clinical cure rate with no emerging safety
concerns. The Company made this decision in consultation with
its medical and scientific advisors based on the compelling
clinical observation that the clinical cure rate for ibezapolstat
was projected to be at least 90% pooled across the open-label Phase
2a and the blinded Phase 2b segments
with no safety concerns noted. Other factors also influenced the
decision, including the cost of maintaining clinical trial sites
and the challenging enrollment environment in the U.S. due to the
COVID-19 pandemic and its aftermath.
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.
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).
According to Stuart Johnson, MD,
Professor of Medicine, Loyola
University (Infectious Disease) and Acurx Scientific
Advisory Board member: "I am very encouraged by the accumulating
data showing that ibezapolstat is clinically comparable to
vancomycin in treating CDI. Since there is only one other
antibiotic besides vancomycin approved for treatment of this
serious disease, there is a clear need for more first-line
therapeutic agents in our armamentarium. Moreover, the advancement
of a small synthetic molecule with a novel bactericidal mechanism
to treat CDI is especially important in this era of emerging
antimicrobial resistance. I am very supportive of the decision by
the Company to end the Phase 2 trial and plan for Phase 3."
Kevin Garey, PharmD, MS,
Professor and Chair, University of
Houston College of Pharmacy, the Principal Investigator for
microbiome aspects of the ibezapolstat clinical trial program and
Acurx Scientific Advisory Board member stated: "These results
confirm and extend our data from the open-label component of the
Phase 2 study and demonstrate the potent activity of ibezapolstat
against C. difficile. I anticipate our ongoing microbiome
studies will confirm the microbiologic eradication of C.
difficile and also compare microbiome changes to advance
knowledge of anti-CDI recurrence properties of ibezapolstat. Our
previous data showed that ibezapolstat unexpectedly spares other
Firmicutes along with the important Actinobacteria phylum necessary
for maintaining a healthy microbiome. These characteristics, in
conjunction with ibezapolstat's ability to favorably increase the
ratio of secondary-to-primary bile acids in the colon, suggest that
ibezapolstat may reduce the likelihood of CDI recurrence when
compared to standard of care vancomycin."
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "These ibezapolstat observed clinical
cure rate results are impressive for an investigational antibiotic
in a Phase 2 trial for CDI. They greatly enhance our scientific
evidence base and, in our view, provide robust support for an
anticipated End-of-Phase 2 FDA Meeting to occur towards end of
first quarter next year with advancement into Phase 3 clinical
trials to follow. Additional analyses of secondary and exploratory
endpoints of the Phase 2b clinical
trial will be forthcoming as soon as available and will include:
Sustained and Extended Clinical Cure rates up to 94 days, systemic
exposure to ibezapolstat, comparative effects on gut microbiome
and, patient reported outcomes."
Mr. DeLuccia added: "I thank all of our clinical trial
investigators and their staffs and patients who participated in the
trial, as well as all our stakeholders whose support contributed to
reaching this important clinical development milestone which is one
step closer to commercialization for patients-in-need of a
promising new class of antibiotic for treatment of CDI."
David P. Luci, the Company's
President and Chief Executive Officer, stated: "Ultimately the
marketplace will determine the antibiotic of choice for front-line
treatment of CDI. But, in our view, as we plan to enter Phase 3
pivotal clinical trials, ibezapolstat appears to have the
properties for ultimate competitive advantage including high
clinical cure rates, low recurrent infection, minimal microbiome
disruption and manufacturing efficiencies to allow competitive
pricing. We believe the market will recognize and appreciate these
advantages."
The Company recognizes the month of November as C.
difficile Awareness Month as designated by the US Centers
for Disease Control and Prevention (CDC) and supports the work of
the Peggy Lillis Foundation and the C Diff Foundation in raising
awareness, educating and advocating for the Prevention, Treatments,
Clinical Trials, and Environmental Safety of Clostridioides
difficile (C. difficile) Infections worldwide.
Please visit their websites:
Peggy Lillis Foundation: https://cdiff.org/
Cdiff Foundation: https://cdifffoundation.org/.
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.
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. 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, an Independent Data Monitoring Committee will not be
required to perform an interim analysis of this Phase 2b trial data as originally planned. 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.
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.
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.
About Ibezapolstat
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 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. 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 clinical stage
biopharmaceutical company focused on developing new
antibiotics for difficult to treat 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.