- Agreement with FDA reached on key elements to move forward with
our international Phase 3 clinical trial program
- Agreement also reached with FDA on complete non-clinical and
clinical development plan for filing of a New Drug Application for
marketing approval
- Planning continues to advance ibezapolstat into international
Phase 3 clinical trials for treatment of C. difficile
Infection (CDI)
- SME (Small and Medium-sized Enterprise) designation has been
granted by the EMA (European Medicines Agency), which allows Acurx
to benefit from fee incentives and other support from the EMA for
EU Marketing Authorization
- Acurx is now preparing to submit requests for guidance to
initiate clinical trials in the European Union, the United Kingdom, Japan and Canada
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation from FDA
STATEN
ISLAND, N.Y., May 15, 2024
/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 the
successful outcome of an End-of-Phase 2 meeting with the U.S. Food
and Drug Administration (FDA), supporting the advancement of
ibezapolstat for the treatment of C. difficile Infection
into Phase 3 studies based on the recently completed Phase 2
clinical trial results.
Key elements for the two Phase 3, non-inferiority, pivotal
trials were confirmed and included agreement on the protocol
design, patient population, primary and secondary endpoints, and
size of the registration safety database. Based on FDA
recommendations, and in anticipation of an EMA Scientific Advice
Meeting, the primary efficacy analysis will be performed using a
Modified Intent-To-Treat (mITT) population consistent with EMA
requirements. This will result in an estimated 450 subjects in the
mITT population, randomized in a 1:1 ratio to either ibezapolstat
or standard-of-care vancomycin, enrolled into the initial Phase 3
trial. The trial design not only allows determination of
ibezapolstat's ability to achieve Clinical Cure of CDI as measured
2 days after 10 days of oral treatment, but also includes
assessment of ibezapolstat's potential effect on reduction of CDI
recurrence in the target population. In the event non-inferiority
of ibezapolstat to vancomycin is demonstrated, further analysis
will be conducted to test for superiority.
Robert J. DeLuccia, Executive Chairman of Acurx,
stated: "We are very pleased with the successful outcome of our End
of Phase 2 meeting with the FDA and to have reached this important
development milestone for our company. We can now proceed with
plans to prepare for initiation of the first international Phase 3
trial. He further stated: "We now have a complete roadmap not only
for the required components of our phase 3 clinical program, but
also what is required for ultimate filing of a New Drug Application
to be followed by submissions for Marketing Authorizations in other
countries around the world."
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 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. 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-positive 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, 2023, 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.