-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-
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.
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version on businesswire.com: https://www.businesswire.com/news/home/20190610005030/en/
Jennifer Vierajviera@tphase.com617-600-7040
Tetraphase Pharmaceuticals (NASDAQ:TTPH)
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