- All 15 ibezapolstat-treated patients in Phase 2b who achieved Clinical Cure (CC) at end of
treatment (EOT) remained free of C. difficile Infection
(CDI) recurrence through one month after EOT, for a Sustained
Clinical Cure (SCC) rate of 100%
- 2 of 14 patients treated with standard of care,
oral vancomycin, experienced recurrent infection within one
month after EOT for a SCC of 86%
- 100% of the 25 ibezapolstat-treated patients in Phase 2
(Phase 2a and 2b) who had CC at EOT
remained cured through one month after EOT
- Further analyses will be forthcoming Q1 2024, as data become
available, regarding other endpoints, from the Phase 2b trial, including Extended Clinical Cure (ECC)
data up to 94 days and comparative effects vs vancomycin on the gut
microbiome
- Preparation underway for meetings with FDA, European Medicines
Agency and other global regulatory agencies and advancement to
international Phase 3 clinical trials
STATEN
ISLAND, N.Y., Dec. 11,
2023 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company
developing a new class of small molecule
antibiotics for difficult-to-treat bacterial infections,
today announced positive Phase 2b
results showing 100% of CDI patients who had CC with ibezapolstat,
the company's late-stage antibiotic candidate, also had SCC.
The efficacy results from the Phase 2 trial (Phase 2a and Phase
2b) are summarized in the table
below:
|
Clinical Cure
(CC)
at EOT
|
Sustained Clinical
Cure
(SCC)
One Month After EOT
for
all evaluable patients
|
Sustained
Clinical Cure* (SCC)
One
Month After EOT
|
ibezapolstat Phase
2a
|
10/10 (100%)
|
10/10 (100%)
|
10/10 (100%)
|
ibezapolstat Phase
2b
|
15/16 (94%)
|
15/16 (94%)
|
15/15 (100%)
|
ibezapolstat Phase 2a
+
Phase 2b
Combined
|
25/26 (96%)
|
25/26 (96%)
|
25/25 (100%)
|
vancomycin
|
14/14 (100%)
|
12/14 (86%)
|
12/14 (86%)
|
*Sustained Clinical
Cure was evaluated only for patients who were CC
at EOT.
|
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 help
validate our ongoing scientific investigations into the anti-CDI
recurrence properties of ibezapolstat including maintenance and
regrowth of healthy gut microbes and bile acid homeostasis. I'm
excited about our ongoing investigations into a new scientific
paradigm optimizing C. difficile antibiotic development to
effectively cure CDI and prevent recurrence."
According to Stuart Johnson, MD,
Professor of Medicine, Loyola
University (Infectious Disease) and Acurx Scientific
Advisory Board member: "Treatment of CDI remains an important unmet
medical need, for 2 reasons. First, the potential for development
of resistance in C. difficile to currently available drugs like
vancomycin threatens our standard therapeutic approach. Second,
recurrent disease is a very serious problem with limited available
treatment options. Although vancomycin is still an effective
treatment, CDI patients treated with oral vancomycin experience a
recurrence rate of 18-23%. Ibezapolstat, by virtue of its novel
mechanism of action, lack of cross-resistance with any marketed
antibiotics, narrow antibacterial spectrum, and selective effects
on the gut microbiome, appears to be a promising potential new
addition to our therapeutic armamentarium. I continue to be
encouraged by the accumulating data showing that ibezapolstat is
clinically comparable to vancomycin in treating CDI and preventing
recurrence."
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "The overall Phase 2 data demonstrate a
high clinical cure rate of 96% together with this 100%
recurrence-free rate is a promising one-two punch to C. difficile
infection for a potential front-line treatment option for patients
with CDI." He further stated: "These two clinical trial endpoints,
together with the Phase 1 and Phase 2a clinical trial data and with
additional data analyses to come, will form the basis for a
comprehensive, solid data package to present to global regulatory
authorities to support advancement to Phase 3 clinical trials
during the second half next year and move one step closer on its
pathway to commercialization."
David P. Luci, President &
CEO of Acurx, stated: "Ibezapolstat continues to demonstrate
success compared to a standard of care, oral vancomycin, to treat
patients with CDI. We anticipate favorable separation between the
two therapeutic options will continue in Q1 2024 with extended
clinical cure and microbiome comparison data. We expect to leverage
this success in a $1 billion plus US
CDI market internationally as we move forward with an international
Phase 3 clinical trial mandate." He added: "The Company also
announced its "Made in America" policy initiative for manufacture
of ibezapolstat capsules for Phase 3 clinical trials and commercial
supply to ensure patients have uninterrupted access to this
potentially life-saving antibiotic mitigating potential supply
chain disruptions."
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 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.
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 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 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:
917-533 146
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.