Phase 3 REASSURE Trial Met Primary Endpoint of
Non-Inferiority to Augmentin®; Demonstrated
Statistical Superiority
Re-submission of NDA to FDA Expected in Q2
2024
Potential to be First Oral Penem Approved in
the U.S.
Management to host a conference call at
8:30 a.m. ET today
DUBLIN and CHICAGO, Jan. 30,
2024 /PRNewswire/ -- Iterum Therapeutics plc (Nasdaq:
ITRM) (Iterum), a clinical-stage pharmaceutical company focused on
developing next-generation oral antibiotics to treat infections
caused by multi-drug resistant pathogens in community settings,
today announced positive topline results from its REASSURE
(REnewed ASsessment of Sulopenem in
uUTI caused by Resistant Enterobacterales)
Phase 3 clinical trial comparing oral sulopenem (sulopenem
etzadroxil combined with probenecid in a bilayer tablet) to oral
Augmentin® (amoxicillin/clavulanate) in adult women with
uncomplicated urinary tract infections (uUTIs).
"We are very pleased to announce positive data from this
confirmatory trial, which was conducted under special protocol
assessment (SPA) agreement with the U.S. Food and Drug
Administration (FDA)," said Corey
Fishman, Iterum's Chief Executive Officer. "With the
positive data from this trial, we plan to resubmit our New Drug
Application (NDA) for oral sulopenem for the treatment of uUTI in
the second quarter of 2024. At the same time, with these results in
hand, we will be focusing on a strategic process to sell, license,
or otherwise dispose of our rights to sulopenem with the goal of
maximizing value for our stakeholders. We believe there is
tremendous value in sulopenem as a potential new, oral antibiotic
for the uUTI indication which has over 30 million infections
annually in the U.S., rising resistance to all currently prescribed
oral antibiotics, and a complete lack of new product innovation
over the last 20 years."
Results demonstrate that oral sulopenem was non-inferior to
Augmentin® with respect to the trial's primary endpoint,
overall response (combined clinical cure plus microbiologic
eradication) at the test-of-cure (TOC) visit in the
microbiological-modified-intent-to-treat susceptible (m-MITTS)
population. Oral sulopenem showed overall success in 61.7% of
patients compared to 55.0% for Augmentin®, demonstrating
statistically significant superiority of oral sulopenem versus
Augmentin®.
The table below summarizes the key efficacy data from the
REASSURE trial at the TOC visit:
|
Sulopenem/probenecid
500 mg/500 mg
BID
N=480
n (%)
|
Augmentin®
(Amoxicillin/clavulanate)
875 mg/125 mg
BID
N=442
n (%)
|
Treatment
Differencei
(95% CI)
|
Overall
Responseii
|
296 (61.7)
|
243 (55.0)
|
6.7 (0.3,
13.0)
|
Clinical
Successiii
|
371 (77.3)
|
339 (76.7)
|
0.6 (-4.8,
6.1)
|
Microbiological
Successiv
|
361 (75.2)
|
295 (66.7)
|
8.5 (2.6,
14.3)
|
|
|
[i]
|
Difference in oral
sulopenem versus Augmentin® in the m-MITTS
population
|
[ii]
|
Combined clinical and
microbiological success (primary endpoint)
|
[iii]
|
Clinical success at TOC
= symptom resolution + no new uUTI symptoms
|
[iv]
|
Eradication of
qualifying uropathogen to <103 CFU/mL at TOC
visit
|
Both oral sulopenem and Augmentin® were well
tolerated in this study with discontinuations due to adverse events
occurring in <1% of patients on both regimens. No serious
adverse events (SAE) were reported in patients receiving oral
sulopenem, while five SAEs occurred in patients receiving
Augmentin®, with no drug-related SAEs. The safety
profile for oral sulopenem was consistent with those observed in
each of the previously conducted Phase 3 trials, with no new safety
signals noted beyond those associated with β-lactams.
Iterum expects to present complete results from the REASSURE
trial at an upcoming scientific meeting.
"In addition to achieving non-inferiority for the primary
endpoint of overall response at the TOC visit in the
Augmentin®-susceptible population in the REASSURE trial,
the lower limit of the 95% confidence interval around the treatment
difference was above zero, indicating statistical superiority of
oral sulopenem over Augmentin® for the treatment of
uUTI. Furthermore, consistent results were observed for all key
secondary efficacy endpoints in this population," said Sailaja Puttagunta, M.D., Iterum's Chief Medical
Officer. "These results bring us one step closer to delivering a
much-needed oral treatment option for women suffering from uUTIs.
In addition, we believe these results, along with evidence from our
prior Phase 3 studies, support the potential of sulopenem in other
indications, such as complicated urinary tract infections
(cUTI)."
Iterum expects to resubmit its NDA for oral sulopenem to the
FDA in the second quarter of 2024. Provided that the
resubmitted NDA addresses all of the deficiencies identified in the
Complete Response Letter (CRL) Iterum received from the FDA in
July 2021, Iterum expects that the
FDA will complete its review and take action six months from the
date the FDA receives the resubmitted NDA (or during the fourth
quarter of 2024).
Conference Call and Webcast Details
Iterum will host a conference call and webcast today,
Tuesday, January 30, 2024, at
8:30 a.m. Eastern Time. The dial-in
information for the call is as follows:
United States: 1 833 470 1428 /
International: 1 404 975 4839
Access code: 781689
The conference call will also be webcast live. The webcast can
be accessed here.
About REASSURE
The REASSURE trial is designed as a non-inferiority (10% margin)
trial comparing oral sulopenem and Augmentin® in the
Augmentin®-susceptible population and is entitled "A
prospective, Phase 3, randomized, multi-center, double-blind study
of the efficacy, tolerability, and safety of oral sulopenem
etzadroxil/probenecid versus oral amoxicillin/clavulanate for
treatment of uncomplicated urinary tract infections (uUTI) in adult
women." If the lower bound of the 95% CI is greater than -10%,
non-inferiority of oral sulopenem over Augmentin would be
concluded. If the lower bound of the 95% CI is greater than 0%,
superiority of oral sulopenem over Augmentin would be concluded.
Patients were randomized to receive either oral sulopenem twice
daily for five days or Augmentin® twice daily for five
days. The primary endpoint was the overall response (clinical and
microbiologic combined response) at Day 12 (+/- 1 day) (TOC visit)
of the trial. The trial enrolled 2,222 patients and is being
conducted under a SPA agreement with the FDA.
About Urinary Tract Infections (UTIs)
UTIs are among the most common bacterial infections encountered
in the community. There are approximately 15 million emergency
room and office visits for symptoms of UTIs and over 30 million
uUTIs treated in the United States
annually, with approximately 30% of those infections caused by a
quinolone non-susceptible organism, and approximately 1% of those
infections caused by pathogens that are resistant to all commonly
available classes of oral antibiotics. As a result, the treatment
of UTIs has become more challenging because of the development of
resistance by pathogens responsible for these infections. uUTIs are
infections of the bladder occurring mainly in women. Half (50%) of
all women experience at least one uUTI at some point in their
lives.
About Iterum Therapeutics plc
Iterum Therapeutics plc is a clinical-stage pharmaceutical
company dedicated to developing differentiated anti-infectives
aimed at combatting the global crisis of multi-drug resistant
pathogens to significantly improve the lives of people affected by
serious and life-threatening diseases around the world. Iterum is
currently advancing its first compound – sulopenem – a novel penem
anti-infective compound, in Phase 3 clinical development with an
oral formulation. Sulopenem also has an IV formulation. Sulopenem
has demonstrated potent in vitro activity against a wide variety of
gram-negative, gram-positive and anaerobic bacteria resistant to
other antibiotics. Iterum has received Qualified Infectious Disease
Product (QIDP) and Fast Track designations for its oral and IV
formulations of sulopenem in seven indications. For more
information, please visit www.iterumtx.com.
Forward-looking Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. These forward-looking statements include, without limitation,
statements regarding the development, therapeutic and market
potential of sulopenem, our ability to address the deficiencies set
out in the complete response letter received in July 2021, the expected timing of resubmission of
the NDA, the expected timing of review by the FDA and Iterum's
strategic process to sell, license, or otherwise dispose of its
rights to sulopenem. In some cases, forward-looking statements can
be identified by words such as "may," "believes," "intends,"
"seeks," "anticipates," "plans," "estimates," "expects," "should,"
"assumes," "continues," "could," "would," "will," "future,"
"potential" or the negative of these or similar terms and phrases.
Forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause Iterum's actual
results, performance or achievements to be materially different
from any future results, performance or achievements expressed or
implied by the forward-looking statements. Forward-looking
statements include all matters that are not historical facts.
Actual future results may be materially different from what is
expected due to factors largely outside Iterum's control, including
uncertainties inherent in the conduct of clinical and non-clinical
development, changes in regulatory requirements or decisions of
regulatory authorities, the timing or likelihood of regulatory
filings and approvals, including the potential resubmission of the
NDA for oral sulopenem, changes in public policy or legislation,
commercialization plans and timelines, if oral sulopenem is
approved, the actions of third-party clinical research
organizations, suppliers and manufacturers, the accuracy of
Iterum's expectations regarding how far into the future Iterum's
cash on hand will fund Iterum's ongoing operations, Iterum's
ability to maintain its listing on the Nasdaq Capital Market, risks
and uncertainties concerning the outcome, impact, effects and
results of Iterum's pursuit of strategic alternatives, including
the terms, timing, structure, value, benefits and costs of any
strategic process and Iterum's ability to complete one at all and
other factors discussed under the caption "Risk Factors" in its
Quarterly Report on Form 10-Q filed with the SEC on November 14, 2023, and other documents filed with
the SEC from time to time. Forward-looking statements represent
Iterum's beliefs and assumptions only as of the date of this press
release. Except as required by law, Iterum assumes no obligation to
update these forward-looking statements publicly, or to update the
reasons actual results could differ materially from those
anticipated in the forward-looking statements, even if new
information becomes available in the future.
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