-Study Examines Microbiology and Hospitalization Outcomes Among
Complicated Intra-Abdominal Infection Patients-
-Data Underscore XERAVA’s Role as an Empiric Treatment Option for
Patients With Complicated Intra-Abdominal Infections-
WATERTOWN, Mass.–(BUSINESS WIRE)–$TTPH #antibioticresistance—Tetraphase
Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical company
focused on developing and commercializing novel tetracyclines to treat
serious and life-threatening conditions, today announced the
presentation of positive data from three studies further evaluating its
lead compound, XERAVA™ (eravacycline), a novel, fully-synthetic
fluorocycline, approved by the U.S. Food and Drug Administration and the
European Medicines Agency for the treatment of complicated
intra-abdominal infections (cIAI), as well as data from a retrospective
study of hospital-based outcomes in cIAI. These data were presented at
the 39th Annual Surgical Infection Society (SIS) Meeting,
held June 5-8, 2019 in Coronado, Calif.
“Data continue to demonstrate that cIAI represents a significant threat
to patients that is exacerbated by growing resistance to many of the
antibiotics commonly used to treat these infections,” said Larry Tsai,
M.D., Chief Medical Officer of Tetraphase Pharmaceuticals. “A
retrospective study that collected multi-year data from patients with
cIAI and positive cultures at approximately 180 hospitals showed a
hospital mortality rate of 7.6%, and a 30-day rehospitalization rate of
11.2%, underscoring the need for more effective empiric treatments for
these life-threatening infections.”
Dr. Tsai added, “The data presented at SIS continue to reinforce the
clinical utility of XERAVA in the treatment of cIAI. With the
versatility to treat both confirmed and empiric cIAI and demonstrated
activity against a broad range of Gram-negative, Gram-positive and
anaerobic bacteria, XERAVA represents an important option in the cIAI
treatment landscape.”
Microbiology and Outcomes of Hospitalization With Intra-Abdominal
Infections in the U.S.: A Retrospective Cohort Study
To better understand the microbiology and outcomes of hospitalization
due to cIAIs, researchers performed a multicenter retrospective cohort
study in the Premier database of approximately 180 hospitals from
2013-2017. All adult patients hospitalized with cIAI and a positive
blood or abdominal culture were identified.
Among 4,453 patients with cIAI and positive cultures, 3,771 (84.7%) had
a Gram-negative and 1,782 (40.0%) had a Gram-positive organism
identified. The majority of cases (n=2,941; 66.0%) were monomicrobial.
Among patients with a polymicrobial infection, 1,118 (25.1%) had two
organisms while 394 (8.8%) had three or more pathogens. Notably,
resistance to third-generation cephalosporins occurred in 7.6% of all
Gram-negative pathogens. The most common Gram-negative pathogens were E.
coli (2,624; 58.9%) and K. pneumoniae (774; 17.4%).
Beyond microbiology, this retrospective study analyzed hospitalization
outcomes. Findings showed that hospital mortality due to cIAI was 7.6%,
and 11.2% of patients were readmitted within 30 days of discharge. The
median (interquartile range) length of stay was 6 (3, 12) days, and
median total cost was $21,148 ($12,051, $43,637). These results
highlight the significant morbidity and mortality associated with cIAI
hospitalizations, as well as the substantial cost burden.
Efficacy of Eravacycline in Non-Appendiceal Complicated
Intra-Abdominal Infections: An Analysis of Two Phase 3 Trials
Compared to complicated appendicitis, cIAIs of non-appendiceal etiology
carry a higher risk for initial treatment failure, prolonged treatment
duration, and increased mortality.1 Researchers hypothesized
that patients with non-appendiceal cIAIs treated with XERAVA would have
similar clinical outcomes when compared to those treated with
carbapenems. A post-hoc analysis of patients diagnosed with cIAI of
non-appendiceal origin from two Phase 3 studies, IGNITE1 and IGNITE4,
was performed to determine clinical outcomes. Clinical cure rates in
patients diagnosed with complicated appendicitis were 89.0% and 88.6% in
patients treated with XERAVA and comparators, respectively. In patients
with non-appendiceal cIAIs treated with XERAVA and comparators, clinical
cure rates were 88.8% and 89.7%, respectively. Across the
non-appendiceal subgroups, clinical outcomes between XERAVA and
comparators were similar.
This pooled analysis suggests that XERAVA is an effective empiric
treatment option for patients with cIAI, including those with specific
higher-risk diagnoses such as peritonitis and intestinal perforation.
2017 Global Surveillance of the In Vitro Activity of Eravacycline
Against Clinical Isolates From Gastrointestinal Infections
In a subset of data from a 2017 global surveillance study, 2,005
non-duplicate, non-consecutive, single-patient gastrointestinal isolates
were analyzed to determine the Minimum Inhibitory Concentration (MIC)
required to inhibit the growth of 50% and 90% of organisms,
respectively, for XERAVA and comparators. Results demonstrated potent in
vitro activity against Enterobacteriaceae with an MIC90
value of 1 mg/L compared to 4 mg/L for tigecycline. XERAVA demonstrated
two- to eight-fold greater potency than tigecycline against Escherichia
coli, Klebsiella spp. and Acinetobacter
baumannii, including against pathogens expressing extended
spectrum beta-lactamases (ESBL). In addition, XERAVA had two- to
four-fold greater potency than tigecycline versus clinically important
Gram-positive pathogens such as methicillin-resistant Staphylococcus
aureus (MRSA) and Enterococcus spp.
These data support that XERAVA is a treatment option for cIAI in
patients who harbor or are at risk for infections due to resistant Enterobacteriaceae.
Factors That Impact Duration of Antibiotic Therapy From Phase 3
Studies of Eravacycline for Intra-Abdominal Infection
A post-hoc analysis of two pooled Phase 3 studies (IGNITE1 and IGNITE4)
of XERAVA examined the impact of certain patient-specific variables on
duration of treatment. Researchers sought to determine whether variables
associated with duration of treatment differed in patients based on the
type of cIAI – complicated appendicitis or non-appendiceal infections.
Patients with cIAI from both Phase 3 studies were randomized (1:1) to
receive XERAVA or a carbapenem. Duration of therapy was discretionary up
to 14 days. Groups were categorized by the following durations: ≤5 days,
6-8 days and >8 days.
Results showed that among all patients, those who received longer
treatment were older (p=0.004), sicker (p<0.001), more likely to have
non-appendiceal infections (p<0.001) and to have undergone open surgery
for infection source control (p<0.001). For patients with complicated
appendicitis, open surgery and polymicrobial infection were associated
with longer treatment (p<0.001), whereas patients with non-appendiceal
infections who had longer length of therapy were more likely to be ill
(p=0.029), to have undergone open surgery (p=0.001) and to have received
prior antibiotics (p=0.001). Further analysis to quantify the impact of
various factors in terms of days of therapy showed that patients who had
laparoscopic surgery for source control had approximately one day less
of therapy, while patients who had a multidrug-resistant Enterococcus
pathogen received 1.3 additional days of therapy.
About XERAVA™
XERAVA (eravacycline for injection) is a tetracycline class
antibacterial indicated for the treatment of complicated intra-abdominal
infections (cIAI) in patients 18 years of age and older. XERAVA was
investigated for the treatment of cIAI as part of the Company’s IGNITE (Investigating
Gram-Negative Infections Treated with Eravacycline)
Phase 3 program. In the first pivotal Phase 3 trial in patients with
cIAI, twice-daily intravenous (IV) XERAVA met the primary endpoint by
demonstrating statistical non-inferiority of clinical response compared
to ertapenem and was well-tolerated. In the second Phase 3 clinical
trial in patients with cIAI, twice-daily IV XERAVA met the primary
endpoint by demonstrating statistical non-inferiority of clinical
response compared to meropenem and was well-tolerated. In both trials,
XERAVA achieved high cure rates in patients with Gram-negative
pathogens, including resistant isolates.
Indications and Usage
XERAVA is indicated for the treatment of complicated intra-abdominal
infections (cIAI) caused by susceptible microorganisms: Escherichia
coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae,
Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium,
Staphylococcus aureus, Streptococcus anginosus group, Clostridium
perfringens, Bacteroides species, and Parabacteroides
distasonis in patients 18 years or older.
Limitations of Use
XERAVA is not indicated for the treatment of complicated urinary tract
infections (cUTI).
Usage
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of XERAVA and other antibacterial drugs, XERAVA should be
used only to treat or prevent infections that are proven or strongly
suspected to be caused by susceptible bacteria. When culture and
susceptibility information are available, they should be considered in
selecting or modifying antibacterial therapy. In the absence of such
data, local epidemiology and susceptibility patterns may contribute to
the empiric selection of therapy.
Important Safety Information
XERAVA is contraindicated for use in patients with known
hypersensitivity to eravacycline, tetracycline-class antibacterial
drugs, or to any of the excipients. Life-threatening hypersensitivity
(anaphylactic) reactions have been reported with XERAVA.
The use of XERAVA during tooth development (last half of pregnancy,
infancy and childhood to the age of eight years) may cause permanent
discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.
The use of XERAVA during the second and third trimester of pregnancy,
infancy and childhood up to the age of eight years may cause reversible
inhibition of bone growth.
Clostridium difficile associated diarrhea (CDAD) has been
reported with use of nearly all antibacterial agents and may range in
severity from mild diarrhea to fatal colitis.
The most common adverse reactions observed in clinical trials (incidence
≥3%) were infusion site reactions (7.7%), nausea (6.5%), and vomiting
(3.7%).
XERAVA is structurally similar to tetracycline-class antibacterial drugs
and may have similar adverse reactions. Adverse reactions including
photosensitivity, pseudotumor cerebri, and anti-anabolic action which
has led to increased BUN, azotemia, acidosis, hyperphosphatemia,
pancreatitis, and abnormal liver function tests, have been reported for
other tetracycline-class antibacterial drugs, and may occur with XERAVA.
Discontinue XERAVA if any of these adverse reactions are suspected.
To report SUSPECTED ADVERSE REACTIONS, contact Tetraphase
Pharmaceuticals Inc., at 1-833-7-XERAVA (1-833-793-7282) or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information for XERAVA at www.XERAVA.com.
About Tetraphase Pharmaceuticals, Inc.
Tetraphase Pharmaceuticals, Inc., is a biopharmaceutical company using
its proprietary chemistry technology to create novel tetracyclines for
serious and life-threatening conditions, including infections caused by
many of the multidrug-resistant bacteria highlighted as urgent public
health threats by the World Health Organization and the Centers for
Disease Control and Prevention. The Company has created more than 3,000
novel tetracycline compounds using its proprietary technology platform.
Tetraphase’s lead product XERAVA™ is approved for the treatment of
complicated intra-abdominal infections by the U.S. Food and Drug
Administration and the European Medicines Agency. The Company’s pipeline
also includes TP-271 and TP-6076, which are in Phase 1 clinical trials,
and TP-2846, which is in preclinical testing for acute myeloid leukemia.
Please visit www.tphase.com
for more company information.
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, including our key
milestones for 2019 and our anticipated cash runway, and other
statements containing the words “anticipates,” “believes,” “expects,”
“plans,” “will” 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 clinical, regulatory and commercial risk
factors discussed in the “Risk Factors” section of our quarterly report
on Form 10-Q for the period ended March 31, 2019, filed with the
Securities and Exchange Commission on May 8, 2019. In addition, the
forward-looking statements included in this press release represent our
views as of June 10, 2019. We anticipate that subsequent events and
developments will cause our views to change. However, while we may elect
to update these forward-looking statements at some point in the future,
we specifically disclaim any obligation to do so.
i Mazsuki JE et al. Surg Infect. 2017; 18(1):1-76.
Contacts
Jennifer Viera
jviera@tphase.com
617-600-7040