Iterum Therapeutics plc (Nasdaq: ITRM), a clinical-stage
pharmaceutical company focused on developing an oral and IV penem
antibiotic to treat infections caused by multi-drug resistant
pathogens in both community and hospital settings, today announced
topline results from its
Sulopenem for
Resistant
Enterobacteriaceae
(SURE) 3 clinical trial in complicated intra-abdominal infections
(cIAI).
The primary U.S. Food and Drug Administration (FDA) endpoint was
clinical response on Day 28 in the micro-MITT population. In this
population, the difference in outcomes was 4.7% with a 95%
confidence interval on that difference of -10.3% to 1.0%.
Non-inferiority required that the lower limit of the difference in
the outcome rates be >-10% for FDA.
|
Sulopenem |
Ertapenem |
Difference (95% Confidence
Interval) |
Test of Cure |
|
|
|
microMITT |
85.5% |
|
90.2% |
|
-4.7% (-10.3, 1.0) |
MITT |
87.2% |
|
90.0% |
|
-2.9% (- 7.7, 2.0) |
Clinically Evaluable |
93.5% |
|
95.7% |
|
-2.0% (-5.7, 1.7) |
Microbiologically Evaluable |
92.5% |
|
95.5% |
|
-3.0% (-7.5, 1.4) |
End of Treatment |
|
|
|
microMITT |
83.5% |
|
85.3% |
|
-1.8% (- 8.1, 4.5) |
MITT |
83.7% |
|
85.4% |
|
-1.7% (-7.1, 3.8) |
Clinically Evaluable |
89.4% |
|
90.0% |
|
-0.7% (-5.6, 4.3) |
Microbiologically Evaluable |
88.5% |
|
88.9% |
|
-0.4% (-6.3, 5.4) |
In a prespecified multiple imputation analysis designed to
address any imbalances in patients with indeterminate outcomes at
the test of cure in the microMITT population, the difference in
outcomes was 4.7% with a 95% confidence interval on that difference
of -9.9% to 0.5%.
In the safety population of 668 patients, treatment related
adverse events were observed in 6.0% and 5.1% of patients on
sulopenem and ertapenem, respectively, with the most commonly
reported drug-related adverse event being diarrhea at 4.5% and
2.4%. Discontinuations were uncommon on both regimens seen in 1.5%
of patients on sulopenem and 2.1% of patients on ertapenem. Serious
adverse events unrelated to study treatment were seen in 7.5% of
patients on sulopenem and 3.6% of patients on ertapenem.
“While the difference in the primary outcome is one patient shy
of the target of -10%, imputing an outcome for the patients with
missing data and the secondary supporting analyses, both at the end
of treatment as well as the test of cure, provide support for the
potential of sulopenem in the treatment of multi-drug resistant
infections,” said Michael Dunne, MD, Chief Scientific Officer at
Iterum Therapeutics. “Over 10% of the patients in this study had a
gram-negative pathogen that was resistant to both quinolones and
β-lactams, the two classes of oral agents that are most commonly
used for step down therapy for this indication. In this era of
rapidly emerging multi-drug resistance, we believe the availability
of sulopenem in its oral and IV formulations would provide the
healthcare system with a much needed option for step-down therapy
from hospital to home.”
“We believe that these topline results, while narrowly missing
the primary endpoint, provide data that emphasize the potential for
sulopenem to help address the growing challenge of antibiotic
resistance,” said Corey Fishman, Chief Executive Officer of Iterum
Therapeutics. “If we obtain positive results in Q1 2020 from
our Phase 3 complicated and uncomplicated urinary tract trials, we
believe that the overall safety and efficacy results from this cIAI
trial would be supportive in an FDA filing for oral and IV
sulopenem and that sulopenem’s market potential remains
robust.”
The multi-center, double-blind SURE 3 randomized patients with
cIAI to receive either IV sulopenem once daily for a minimum of
five days followed by oral sulopenem/probenecid twice daily to
complete 7 to10 total days of treatment, or IV ertapenem once daily
for a minimum of five days followed by oral ciprofloxacin twice
daily along with oral metronidazole four times daily or, for those
patients with ciprofloxacin-resistant organism at baseline,
amoxicillin-clavulanate twice daily. The primary endpoint was based
on clinical response at Day 28 in patients with a positive
intra-abdominal culture at baseline, consistent with recent FDA
Guidelines for Development of Drugs for intra-abdominal infections.
Clinical outcome at Day 28 was noted as cure for those patients who
were alive, had resolution in signs and symptoms of the index
infection and for whom no new antibiotics or interventions for
treatment failure were required.
About Complicated Intra-abdominal
Infections
cIAIs are the second leading cause of infection-related
mortality in intensive care units.1 IAI is a broad term that
encompasses a number of infections, including peritonitis,
diverticulitis, cholecystitis, cholangitis, and pancreatitis. These
complicated infections extend from a gastrointestinal source, such
as the appendix or the colon, into the peritoneal space and can be
associated with abscess formation. Among approximately 350,000 cIAI
patients in the United States each year, broad spectrum antibiotics
are generally administered as first line treatment; treatment
failure is more common due to the serious nature of these
infections. Carbapenems are recommended by the Infectious Disease
Society of America (IDSA) guidelines for empiric treatment of
intra-abdominal infections.
1
https://www.uspharmacist.com/article/intraabdominal-infections-in-adults
About Sulopenem
Sulopenem, a novel penem anti-infective compound with oral and
IV formulations, 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 will help address the
significant clinical and economic need for new oral antibiotics
that enable the avoidance of hospitalization or facilitate early
hospital discharge by providing continuity-of-care step-down
therapy. The safety profile of IV sulopenem has been documented in
a Phase 2 program. Given these results, oral and IV sulopenem are
being evaluated in three pivotal Phase 3 clinical trials of
uncomplicated urinary tract infections, complicated urinary tract
infections and complicated intra-abdominal infections.
The FDA has granted Special Protocol Agreements (SPA) and
Qualified Infectious Disease Product (QIDP) designations for oral
and IV 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
oral and IV formulations. 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 may contain forward-looking statements. These
forward-looking statements include, without limitation, statements
regarding the development, therapeutic and market potential of
sulopenem and the timing, progress and results of clinical trials
and regulatory submissions. 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,” “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
conduct of clinical trials, clinical trial patient enrollment,
availability and timing of data from clinical trials, changes in
regulatory requirements or decisions of regulatory authorities,
including uncertainties associated with regulatory review of
clinical trials and applications for marketing approval, changes in
public policy or legislation, the actions of third-party clinical
research organizations, suppliers and manufacturers,
commercialization plans and timelines, if approved, the sufficiency
of Iterum Therapeutics’ cash resources and its ability to continue
as a going concern, and other factors discussed under the caption
“Risk Factors” in Iterum Therapeutics’ most recently filed
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) on November 12, 2019, 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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