Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical
company focused on developing and commercializing novel antibiotics
to treat life-threatening multidrug-resistant (MDR) infections,
recently reported data on eravacycline, which is currently under
review by the United States Food and Drug Administration (FDA) and
the European Medicines Agency (EMA) for the treatment of
complicated intra-abdominal infections (cIAI), as well as data for
TP-6076, its second-generation candidate targeting MDR
Gram-negative bacteria, which is currently in phase 1 clinical
testing. These data were presented at the American Society for
Microbiology (ASM) Microbe 2018 Annual Meeting, held June 7-11,
2018 in Atlanta, GA.
“For the first time, we are sharing a pooled analysis of our
IGNITE1 and IGNITE4 studies of eravacycline and are pleased to show
that favorable clinical and microbiological responses were observed
for eravacycline against Enterobacteriaceae and Acinetobacter
baumannii, including those demonstrating resistant phenotypes and
genotypes such as MDR and extended spectrum beta-lactamase (ESBL)
production,” said Guy Macdonald, President and Chief Executive
Officer of Tetraphase. “Further, in a global surveillance study,
eravacycline exhibited potent in vitro activity against
Enterobacteriaceae, A. baumannii, S. maltophilia and clinically
important Gram-positive organisms. In fact, the MIC90 of
eravacycline against Enterobacteriaceae was up to four-fold lower
than tigecycline, including against MDR isolates. These data lend
additional support to our conviction that eravacycline has the
potential to be an important new treatment option for patients with
these serious and often life-threating infections.”
Mr. Macdonald added, “We are also encouraged by the significant
in vitro potency observed in the data presented on TP-6076 at ASM
Microbe. The TP-6076 MIC50/90 values for Enterobacteriaceae and A.
baumannii were 0.063/0.5 µg/mL and 0.016/0.063 µg/mL, respectively.
These data demonstrate that TP-6076 retained potency against
several emergent resistance types and support our belief that it is
a promising candidate for the treatment of MDR Gram-negative
pathogens.”
Microbiological Efficacy of Eravacycline Against
Enterobacteriaceae and Acinetobacter baumannii, Including MDR
Isolates: A Pooled Analysis From IGNITE1 and IGNITE4, Two Phase 3
Trials of Complicated Intra-Abdominal Infection
This poster presentation is the first post-hoc analysis of
IGNITE1 and IGNITE4 – two of the Investigating
Gram-Negative
Infections Treated with
Eravacycline (IGNITE) phase 3 trials for
eravacycline. IGNITE1 and IGNITE4 were randomized, double-blind,
double-dummy, multi-center studies assessing the efficacy and
safety of intravenous (IV) eravacycline compared to ertapenem and
meropenem, respectively, in patients with cIAI. IGNITE1 included
541 patients and used a 10% non-inferiority margin, while IGNITE4
included 500 patients and used a 12.5% non-inferiority margin. Both
IGNITE1 and IGNITE4 met the primary endpoints of clinical cure with
eravacycline achieving high cure rates in patients with
Gram-negative and Gram-positive pathogens, including resistant
isolates.
The primary objective of the pooled analysis was to compare the
clinical and microbiological responses at the test-of-cure (TOC)
visit for subjects in the two treatment groups, with an emphasis on
the response of MDR pathogens to eravacycline.
For patients with cIAI caused by Enterobacteriaceae, the overall
favorable clinical and microbiological response rates among pooled
eravacycline-treated subjects were 88.2% and 86.3%, respectively.
Notably, in patients with infections due to ESBL-producing
Enterobacteriaceae, eravacycline demonstrated a favorable
microbiologic response rate of 88.9%. For patients with cIAI caused
by A. baumannii, of which most strains were MDR, the overall
favorable clinical and microbiological response rate among pooled
eravacycline-treated subjects was 100%.
In vitro Activity of Eravacycline and
Comparators Against Enterobacteriaceae, Acinetobacter baumannii,
Stenotrophomonas maltophilia, Including MDR Isolates, Collected
Globally in 2016
Global clinical isolates were collected during a 2016
surveillance study with the purpose of evaluating the activity of
eravacycline against isolates of Enterobacteriaceae, A. baumannii
(including carbapenem-resistant A. baumannii [CRAB]),
Stenotrophomonas maltophilia, Staphylococcus aureus (including
methicillin-resistant S. aureus [MRSA]), and Enterococcus spp.,
including those that are MDR. Results found the eravacycline
MIC50/90 for all Enterobacteriaceae (n=3,157) was 0.25/1 µg/ml, and
for MDR-Enterobacteriaceae (n=666) was 0.5/2 µg/ml, respectively.
Notably, the MIC90 of eravacycline against Enterobacteriaceae was
up to four-fold lower than that of tigecycline, including against
MDR isolates. Eravacycline also demonstrated potent in vitro
activity with MIC90 values more than eight-fold lower than
tigecycline against A. baumannii. Eravacycline also showed potent
in vitro activity against clinically important Gram-positive
organisms including MRSA and Enterococcus spp.
Eravacycline In Vitro Activity Against Clinical Isolates
Obtained in the United States in 2016 From Urinary and
Gastrointestinal Sources, Including Drug Resistant
Pathogens
In a subset of data from the 2016 global surveillance study, 482
gastrointestinal and 715 genitourinary isolates from sites in the
U.S. were analyzed to determine the MIC50 and MIC90 values for
eravacycline and comparators. Results indicated potent in vitro
activity against Enterobacteriaceae, in gastrointestinal and
genitourinary isolates, with MIC90 values of ≤ 1mg/L. Eravacycline
demonstrated four- to eight-fold greater potency than tigecycline
against Escherichia coli and Klebsiella pneumoniae, two of the most
common isolates in cIAI infections. In addition, eravacycline also
had greater potency than tigecycline versus clinically important
Gram-positive pathogens such as MRSA and Enterococcus spp.
TP-6076 is Active Against Bacterial Isolates Carrying
Emergent Resistance Types
This poster presentation described data from a study in which
TP-6076 was screened against Enterobacteriaceae and A. baumannii
isolates from the U.S. Centers for Disease Control and Prevention
(CDC) Antimicrobial Resistance Bank and other clinical sources and
analyzed for activity against various resistance types. TP-6076 was
assayed for activity against isolates carrying various RNA
methylase genes, genes conferring fosfomycin resistance,
tetracycline efflux pump genes, porin mutations and isolates
resistant to ceftazidime-avibactam. Results found TP-6076 MIC50/90
values for resistant pathogens were 0.063/0.5 µg/ml for
Enterobacteriaceae and 0.016/0.063 µg/ml for A. baumannii. These
data highlight the consistency of TP-6076’s potency in the presence
of resistance mechanisms.
TP-6076 is a novel, synthetic, fluorocycline antibiotic
candidate being developed for the treatment of serious and
life-threatening bacterial infections, including those caused by
pathogens otherwise resistant to current treatment options. It has
demonstrated potent in vitro activity against MDR bacteria
including carbapenem-resistant Enterobacteriaceae and
carbapenem-resistant A. baumannii. In a single-ascending dose
study, TP-6076 was found to have positive safety and
pharmacokinetic data. It is currently in a phase 1
multiple-ascending dose study.
About EravacyclineEravacycline is a novel,
fully-synthetic fluorocycline antibiotic being developed for the
treatment of cIAI and other serious infections, including those
caused by MDR pathogens that have been highlighted as urgent public
health threats by both the World Health Organization and the CDC.
Eravacycline has demonstrated potent activity against MDR
pathogens, including carbapenem-resistant Enterobacteriaceae,
Acinetobacter baumannii, and colistin-resistant bacteria carrying
the mcr-1 gene.
Eravacycline was investigated for the treatment of cIAI as part
of the Company's IGNITE phase 3 program. In IGNITE1, a pivotal
phase 3 trial in patients with cIAI, twice-daily IV eravacycline
met the primary endpoint by demonstrating statistical
non-inferiority of clinical response compared to ertapenem, was
well-tolerated and achieved high cure rates in patients with
Gram-negative pathogens, including resistant isolates. The IGNITE1
data is serving as the basis of the MAA for IV eravacycline for the
treatment of patients with cIAI now under review by the EMA. In
IGNITE4, a second phase 3 clinical trial in patients with cIAI,
twice-daily IV eravacycline met the primary endpoint by
demonstrating statistical non-inferiority of clinical response
compared to meropenem, was well-tolerated and achieved high cure
rates. The Company has used the results from IGNITE1 and IGNITE4 to
support a New Drug Application (NDA) with the FDA for IV
eravacycline in cIAI. The NDA is currently under review with the
FDA with a Prescription Drug User Fee Act (PDUFA) goal date of
August 28, 2018. In clinical trials to date, eravacycline has been
administered to more than 2,700 patients. Eravacycline has not been
approved for commercial use.
About Tetraphase Pharmaceuticals,
Inc.Tetraphase is a biopharmaceutical company using its
proprietary chemistry technology to create novel antibiotics for
serious and life-threatening bacterial infections, including those
caused by many of the MDR bacteria highlighted as urgent public
health threats by the CDC. The Company has created more than 3,000
novel tetracycline compounds using its proprietary technology
platform. Tetraphase's pipeline includes three antibiotic clinical
candidates: eravacycline, which has completed phase 3 clinical
trials and is under review for potential approval in complicated
intra-abdominal infections by the FDA and the EMA, and TP-271 and
TP-6076, which are in phase 1 clinical trials. Please visit
www.tphase.com for more company information.
Forward-Looking StatementsAny statements in
this press release about our future expectations, plans and
prospects, including statements regarding our strategy, future
operations, prospects, plans and objectives, 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: whether the Company's regulatory
submission will receive approval from the United States Food and
Drug Administration or equivalent foreign regulatory agencies;
whether, if any clinical candidate, including eravacycline obtains
approval, it will be successfully distributed and marketed; and
other factors discussed in the "Risk Factors" section of our
quarterly report on Form 10-Q for the period ended March 31,
2018, filed with the Securities and Exchange Commission on May 3,
2018. In addition, the forward-looking statements included in this
press release represent our views as of June 11, 2018. 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.
Contact:Tetraphase PharmaceuticalsJennifer
Viera617-600-7040jviera@tphase.com
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