- Following the previously announced successful End of Phase 2
Meeting achieving agreement with FDA on non-clinical and clinical
Phase 3-readiness, Acurx has now also received written positive
feedback from FDA regarding acceptability of our CMC (Chemistry
Manufacturing and Controls) plan and data package proposed to
support the Phase 3 clinical program
- Acurx has initiated the Scientific Advice procedure with the
European Medicines Agency (EMA) to discuss the readiness for
initiation of the Phase 3 clinical program in the European Union
(EU). Acurx has been notified that we should expect to receive the
final written advice letter in the coming few weeks
- Acurx is also in the process of discussing the pediatric
development plans for ibezapolstat in C. difficile Infection
with FDA and EU health authorities, per regulatory
requirements.
- Phase 3 international trial planning continues to advance,
using AI and other state-of-the-art techniques to identify and
qualify clinical trial sites with the highest potential for patient
enrollment
- Acurx is also preparing to request regulatory guidance to
initiate clinical trials in Japan,
Canada and the United Kingdom
- Ibezapolstat has previously been granted FDA QIDP and
Fast-Track Designation from FDA and Acurx has received SME (Small
and Medium-sized Enterprise) designation by the EMA to benefit from
fee incentives and other support from the EMA for EU Marketing
Authorization
STATEN
ISLAND, N.Y., Dec. 9, 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,
with its lead antibiotic candidate, ibezapolstat,
preparing to advance to international Phase 3 clinical trials to
treat patients with C. difficile
Infection (CDI). The Company today announced
updates on Phase 3 Readiness for Ibezapolstat in C.
difficile Infection based on recent FDA and EMA
Communications.
Written communications are used by both regulatory agencies in
lieu of face-to-face or teleconference/video conferences when these
agencies determine that a written response to the sponsor's
questions would be the most appropriate means for providing
feedback and advice to the sponsor. (FDA Guidance on Formal
Meetings, EMA Guidance on Centralised Procedure)
Acurx's Executive Chairman, Bob DeLuccia, stated:
"We are very pleased with these latest favorable communications
from both regulatory agencies and in our opinion are a testament to
the strength of our clinical data to date, our robust regulatory
submissions, and adherence to current regulatory guidance." He
further added: "We anticipate, and are confident, that with final
EMA advice for our ibezapolstat Phase 3 trials for adult patients
with CDI and the pediatric development plans from both regulatory
agencies, Acurx will have a clear international roadmap for conduct
of our Phase 3 program and, if successful, requirements for US NDA
submission and EU Marketing Authorization."
Acurx has previously announced that it had a successful FDA
End-of-Phase 2 Meeting and Phase 3 Readiness for
ibezapolstat for the Treatment of
C. difficile Infection. Agreement with FDA was
reached on key elements to move forward with its international
Phase 3 clinical trial program. Agreement was also reached
with FDA on the complete non-clinical and clinical development plan
for filing of a New Drug Application (NDA) for marketing approval.
Planning continues to advance ibezapolstat into international Phase
3 clinical trials for treatment of C.
difficile Infection (CDI). Acurx is also preparing to
submit requests for regulatory guidance to initiate clinical trials
in the European Union, to be followed by requests to be
submitted in the United Kingdom,
Japan and Canada.
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-reat
(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.
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. (Link to
Clinicaltrials.gov/NCT042447542) 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. from study centers
in the United States. In the Phase 2a trial segment,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).
In the Phase 2b trial segment,
which was discontinued due to success,
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).
In the Phase 2 clinical trial (both trial segments), the Company
also evaluated 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.
Furthermore, ibezapolstat-treated patients showed lower
concentrations of fecal primary
bile acids, and higher beneficial ratio of secondary
to primary bile acids than vancomycin-treated patients.
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:
0.3390/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). In the Ph2b
trial, ibezapolstat-treated patients showed lower concentrations of
fecal primary bile acids, and higher beneficial ratio of secondary
to primary bile acids than vancomycin-treated patients.
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), drug-resistant Streptococcus pneumoniae (DRSP)
and B. anthracis (anthrax; a Bioterrorism Category A
Threat-Level pathogen). Acurx's lead product candidate,
ibezapolstat, for the treatment of C. difficile Infection is
Phase 3 ready with plans in progress to begin international
clinical trials next year. The Company's preclinical pipeline
includes development of an oral product candidate for treatment of
ABSSSI (Acute Bacterial Skin and Skin Structure Infections), upon
which a development program for treatment of inhaled anthrax is
being planned in parallel.
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.