Iterum Therapeutics plc (Nasdaq: ITRM), 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 topline results
from its
Sulopenem
for
Resistant
Enterobacteriaceae
(SURE) 1 clinical trial for the treatment of Uncomplicated Urinary
Tract Infections (uUTI). Sulopenem is a novel anti-infective
compound that, if approved, would be the first penem antibiotic
with an oral formulation indicated for treatment of uUTI.
In SURE1, there were two independent primary endpoints, with
achievement of either of those endpoints expected to provide a
potential path to marketing approval based on previous discussions
with the U.S. Food and Drug Administration (FDA). In the
population of patients with baseline pathogens resistant to
quinolones, sulopenem achieved the related primary endpoint by
demonstrating superiority to ciprofloxacin, providing substantial
evidence of a treatment effect in patients with uUTI. With a
p-value of <0.001, this result was highly statistically
significant. In the second population of patients with organisms
susceptible to quinolones, sulopenem was not non-inferior to
ciprofloxacin and did not achieve the related primary endpoint,
with the difference in outcomes driven by the rate of asymptomatic
bacteriuria post treatment. In SURE1, sulopenem was well
tolerated with a favorable safety profile, consistent with the
SURE2 and SURE3 trials.
“We are extremely pleased to have a potential path to approval
for sulopenem in uUTI. Approximately 5-6 million urinary
tract infections in the U.S. every year are caused by quinolone
resistant pathogens. If approved, sulopenem would provide a
treatment option for women with infections due to these resistant
pathogens,” said Corey Fishman, Chief Executive Officer of Iterum
Therapeutics. “Sulopenem is the first new oral antibiotic to
demonstrate success in treating uUTIs in a phase 3 trial in over
twenty years.” Mr. Fishman continued, “We anticipate a pre-NDA
meeting with the FDA in the third quarter of 2020 to discuss a path
forward.”
Michael Dunne, M.D., Chief Scientific Officer of Iterum
Therapeutics, stated, “Superiority trials to define the
effectiveness of novel antibacterial agents are rarely performed
but remain the ultimate test for defining the value of a new agent
in an area of high unmet medical need. Sulopenem has demonstrated
efficacy in the treatment of UTI due to a quinolone resistant
organism, a scenario found in almost 30% of all urinary tract
infections in women in the United States today.”
The randomized, multi-center, double-blind SURE1 clinical trial
enrolled 1,670 patients to measure efficacy, tolerability, and
safety of oral sulopenem/probenecid for the treatment of uUTI in
adult women. Patients were randomized to receive either oral
sulopenem/probenecid twice daily for five days of treatment, or
oral ciprofloxacin twice daily for three days of
treatment. The End of Treatment (EOT) visit occurred on Day 5
and the Test of Cure Visit (TOC) at Day 12. Two independent
populations were prespecified and tested for an overall response of
success at the TOC: a quinolone resistant population being assessed
for superiority, defined as a p value <0.05, and a quinolone
susceptible population being tested for non-inferiority, based on
the lower limit of the 95% confidence interval (CI) for the
difference in the microbiologic-modified intent to treat population
being greater than -10%. A prespecified analysis of the outcome in
both susceptible and non-susceptible patients combined was also
performed to describe the overall results of treatment of uUTI with
sulopenem relative to ciprofloxacin. The following table sets
forth the topline results from the trial.
Micro-MITT population |
Sulopenemn/N (%) |
Ciprofloxacin n/N(%) |
Difference (%)(95% CI) |
P value |
Quinolone Non-susceptible Population |
Overall Response (TOC) |
92/147
(62.6%) |
50/139
(36.0%) |
26.6%
(15.1, 37.4) |
<
0.001 |
Reason for Failure: Asymptomatic bacteriuria |
27
(18.4%) |
38
(27.3%) |
|
|
Clinical Response (TOC) |
122/147
(83.0%) |
87/139
(62.6%) |
20.4%
(10.2, 30.4) |
<
0.001 |
Overall Response (EOT) |
95/147
(64.6%) |
42/139
(30.2%) |
34.4%
(23.1, 44.8) |
<
0.001 |
Quinolone Susceptible Population |
Overall Response (TOC) |
247/370
(66.8%) |
326/415
(78.6%) |
-11.8%
(-18.0, -5.6) |
|
Reason for Failure: Asymptomatic bacteriuria |
47
(12.7%) |
16
(3.9%) |
|
|
Clinical Response (TOC) |
300/370
(81.1%) |
349/415
(84.1%) |
-3.0%
(-8.4, 2.3) |
|
Overall Response (EOT) |
240/370
(64.9%) |
271/415
(65.3%) |
-0.4%
(-7.1, 6.2) |
|
Combined (Quinolone Susceptible and Quinolone
Non-susceptible Populations) |
Overall Response (TOC) |
339/517
(65.6%) |
376/554
(67.9%) |
-2.3%
(-7.9, 3.3) |
|
Reason for Failure: Asymptomatic bacteriuria |
74
(14.3%) |
54
(9.7%) |
|
|
Clinical Response (TOC) |
422/517
(81.6%) |
436/554
(78.7%) |
2.9%
(-1.9, 7.7) |
|
Overall Response (EOT) |
335/517
(64.8%) |
313/554
(56.5%) |
8.3% (2.4,
14.1) |
|
“The difference in the overall response to treatment in the
population of patients with a quinolone susceptible baseline
pathogen was driven to a large degree by a greater amount of
asymptomatic bacteriuria in the sulopenem treated patients relative
to those receiving ciprofloxacin,” observed Dr. Dunne. “This
same finding was observed in the recently completed Phase 3
clinical trial of sulopenem in complicated urinary tract
infections, SURE2. In that study, the difference in outcome
between ertapenem and sulopenem was driven largely by the post
therapy rate of asymptomatic bacteriuria and, notably, was lower
only in those patients who received ertapenem followed by
ciprofloxacin and not in any other pairwise comparison with
sulopenem or ertapenem treated patients. The clinical significance
of post treatment asymptomatic bacteriuria and its relationship to
oral dosing with ciprofloxacin will be the focus of additional
investigation.”
In the safety population of 1,660 patients, treatment related
adverse events were observed in 11.4% and 11.9% of patients on
sulopenem and ciprofloxacin, respectively. The most commonly
reported adverse events were diarrhea, 7.3% and 7.6%, nausea, 3.4%
and 4.0%, and headache 2.2% and 2.2%, for sulopenem and
ciprofloxacin patients, respectively. Discontinuations due to
adverse events were uncommon on both regimens and were seen in 1.1%
of patients on sulopenem and 1.5% of patients on ciprofloxacin.
Serious adverse events (SAE) were seen in 0.6% of patients on
sulopenem with no drug-related SAE and 0.4% of patients on
ciprofloxacin with one drug-related SAE.
Based on these trial results, the Company plans to request a
pre-NDA meeting with the FDA to discuss its filing strategy.
In parallel, the Company is also evaluating its corporate,
organizational, strategic, financial and financing alternatives
with the goal of maximizing value for its stakeholders, while
prudently managing its resources.
About Urinary Tract InfectionsUTIs result in
13.5 million office or emergency room visits and 21 million
prescriptions in the U.S. annually. According to the U.S. Centers
for Disease Control and Prevention (CDC), multidrug resistant
Escherichia coli, the cause of many serious infections, including
UTIs, are a growing concern in the U.S. where at least two million
people become infected with bacteria that are resistant to
antibiotics and at least 23,000 people die each year as a direct
result of these infections. The effectiveness of common antibiotics
used to treat UTIs has decreased, with approximately one-third of
medications prescribed for UTIs failing, including
fluoroquinolones, penicillins, and cephalosporins. Patients who are
elderly, female or diagnosed with diabetes are at an elevated risk
for UTIs and for uUTIs resistant to commonly used antibiotics.
Fifty to sixty percent of women are likely to be affected by a UTI
in their lifetime, and nearly 30 percent will suffer a
recurrence.
About Sulopenem
Sulopenem, a novel oral penem anti-infective compound, has
demonstrated potent in vitro activity against a wide
variety of gram-negative, gram-positive and anaerobic bacteria
resistant to other antibiotics. If approved, sulopenem would help
address the significant clinical and economic need for new oral
antibiotics that enable the avoidance of hospitalization. The
safety profile of IV sulopenem has been previously documented in a
Phase 2 program. Given these results, oral sulopenem is being
evaluated in this Phase 3 clinical trial for uncomplicated urinary
tract infections.
The U.S. Food and Drug Administration (FDA) has granted Special
Protocol Agreements (SPA) and Qualified Infectious Disease Product
(QIDP) designations for sulopenem in accordance with the Generating
Antibiotics Incentives Now (GAIN) Act, which provides five years of
additional regulatory exclusivity and expedited Fast Track FDA
review.
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
Therapeutics is advancing its first compound, sulopenem, a novel
penem anti-infective compound, in Phase 3 clinical development with
an oral 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
Therapeutics 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 http://www.iterumtx.com.
Forward-looking Statements
This press release contains forward-looking statements. These
forward-looking statements include, without limitation, statements
regarding the development, therapeutic and market potential of
sulopenem, our expectations regarding a potential path forward for
marketing approval of sulopenem for uUTI and with respect to the
overall regulatory process and our evaluation of corporate,
organizational, strategic and financial and financing alternatives.
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 Therapeutics’ 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 Therapeutics’ control, including the uncertainties
inherent in the initiation and conduct of clinical trials,
availability and timing of data from clinical trials, changes in
regulatory requirements or decisions of regulatory authorities, the
Company’s ability to apply for regulatory approval, changes in
public policy or legislation, commercialization plans and
timelines, if sulopenem is approved, the actions of third-party
clinical research organizations, suppliers and manufacturers, the
accuracy of our expectations regarding how far into the future our
cash on hand will fund our ongoing operations, the sufficiency of
our cash resources and our ability to continue as a going concern,
the impact of COVID-19 and related responsive measures thereto,
risks and uncertainties concerning the outcome, impact, effects and
results of the Company’s evaluation of corporate, organizational,
strategic, financial and financing alternatives, including the
terms, timing, structure, value, benefits and costs of any
corporate, organizational, strategic, financial or financing
alternative and the Company’s ability to complete one at all, risks
and uncertainties related to the impact of this announcement on the
Company’s business, financial condition, results of operations and
the price of the Company’s securities, and other factors discussed
under the caption “Risk Factors” in its most recently filed
Quarterly Report on Form 10-Q, and other documents filed with the
SEC from time to time. Forward-looking statements represent Iterum
Therapeutics’ beliefs and assumptions only as of the date of this
press release. Except as required by law, Iterum Therapeutics
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.
Investor Contact:Judy Matthews Chief
Financial Officer 312-778-6073IR@iterumtx.com
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