- Acurx has now received positive written responses from the
EMA (European Medicines Agency) under its Scientific Advice
Procedure that the clinical, non-clinical and CMC (Chemistry
Manufacturing and Controls) information package submitted supports
advancement of the ibezapolstat Phase 3 program
- The responses also included guidance on ibezapolstat's
regulatory pathway for a Marketing Authorization Application for
ibezapolstat in CDI
- With mutually consistent feedback from both EMA and FDA,
Acurx is well positioned to commence our international Phase 3
registration program
- 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., Jan. 6, 2025
/PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP)
("Acurx" or the "Company") is 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
that it has received positive
regulatory guidance
from the EMA during its Scientific Advice
Procedure that the clinical, non-clinical and CMC (Chemistry
Manufacturing and Controls) information package submitted supports
advancement of the ibezapolstat Phase 3 program. The information
package supporting the Phase 3 program included details on Acurx's
two planned Phase 3 clinical trials (designed as non-inferiority
trials vs vancomycin), the patient population, primary endpoint of
Clinical Cure, sample size, statistical analysis plan and the
overall registration safety database.
Acurx's Executive Chairman, Bob
DeLuccia, stated: "We are appreciative of the EMA's
constructive suggestions, and we will proactively incorporate them
into our global registration plan. He further stated: "We are very
pleased with the latest favorable communications from both
regulatory agencies which provide a straightforward international
roadmap for conduct of our Phase 3 program and ultimate
requirements for a US NDA (New Drug Application) submission and EU
Marketing Authorization Application."
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 previously announced it had a successful End of Phase 2
Meeting achieving agreement with FDA on non-clinical and clinical
Phase 3-readiness, including written positive feedback regarding
acceptability of its CMC (Chemistry Manufacturing and Controls)
plan and data package proposed to support the Phase 3
clinical program. In addition, Acurx had initiated the Scientific
Advice procedure with the EMA to discuss the readiness for
initiation of the Phase 3 clinical program in the EU. Acurx
is 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. The primary efficacy
analysis will be performed using a Modified Intent-To-Treat (mITT)
population. 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: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). 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.
