Omadacycline Concentrations Exceed Tigecycline Levels in Lungs and Epithelial Lining Fluid According to Pharmacokinetic/Pharm...
April 25 2017 - 6:30AM
Paratek Pharmaceuticals, Inc. (Nasdaq:PRTK) today presented new
data from a Phase 1 study confirming that its once-daily oral and
IV, broad spectrum investigational antibiotic omadacycline
effectively penetrates lung tissue and epithelial lining fluid and
has a broad antimicrobial activity against those bacteria most
commonly associated with community-acquired bacterial pneumonia
(CABP). Data from a second Phase 1 study evaluating the safety of
omadacycline compared to tigecycline reported no serious adverse
events following IV treatment with either compound and reported
that omadacycline was associated with a lower incidence of
gastrointestinal adverse events compared to tigecycline. The new
findings were presented at the annual meeting of the European
Congress of Clinical Microbiology and Infectious Diseases (ECCMID
2017) in Vienna, Austria.
“Intravenous dosing of omadacycline at 100 mg
produced steady-state concentrations in the plasma, epithelial
lining fluid (ELF), and alveolar cells (AC) that were three-fold
higher than tigecycline in healthy subjects. Our observed
lung concentrations along with the minimum inhibitory concentration
values for respiratory pathogens support the recent results of
omadacycline being as effective as moxifloxacin in the treatment of
patients with community-acquired bacterial pneumonia,” said Keith
Rodvold, Pharm.D., professor in the College of Pharmacy,
Co-Director of the Section of Infectious Diseases Pharmacotherapy
at University of Illinois at Chicago.
“Throughout our clinical development program, we
have worked to generate a thorough understanding of all aspects of
omadacycline and share that information with the scientific and
clinical community,” said Evan Loh, M.D., President, Chief
Operating Officer and Chief Medical Officer, Paratek. “These data
add to the growing body of evidence to support omadacycline as an
effective agent in the treatment of serious acquired bacterial
infections, particularly where resistance is of concern to
prescribing physicians.”
Phase 1 Bronchoalveolar Lavage
StudyThe Phase 1 PK/PD study compared serial plasma
concentrations of omadacycline and tigecycline in healthy adults.
Subjects receiving omadacycline (n=41) received 100 mg IV every 12
hours for 2 doses then 100 mg IV once-daily; subjects in the
tigecycline arm (n=17) received a 100 mg IV loading dose followed
by 50 mg IV every 12 hours. To assess the concentration of both
omadacycline and tigecycline in epithelial lining fluid (ELF) and
alveolar macrophages (AM), bronchoalveolar lavage (BAL) was
performed on all subjects.
The AUC0-24/MIC90 ratios for omadacycline were
greater than tigecycline across all measurements. Specific results
showed omadacycline plasma ratios to be 3.2-fold higher (97.8 vs.
30.8) for S. pneumoniae and MSSA and 1.5-fold higher (46.9 vs.
30.8) for MRSA. The AUC0-24/MIC90 ratios in the ELF were 2.7-fold
higher for omadacycline (143.6 vs. 52.7) for S. pneumoniae and MSSA
and 1.3-fold higher (68.9 vs. 52. 7) for MRSA. AM ratios for L.
pneumophila were 126-fold higher for omadacycline.
Phase 1 Safety and Tolerability
StudyIn an open-label safety study presented yesterday, 63
healthy adults were randomized to omadacycline (n=42) or
tigecycline (n=21). Dosing was similar to the PK/PD study and
treatment duration was four days with a follow up assessment
conducted 7 to 14 days after the final dose. Treatment emergent
adverse events were mild-to-moderate in both groups and included
headache, nosebleed (epistaxis), nausea, decreased appetite and
vomiting. Fewer individuals in the omadacycline group reported
gastrointestinal adverse event. There were two discontinuations in
the tigecycline group due to nausea that were considered related to
study drug. No omadacycline subjects discontinued study
treatment due to adverse events.
About Paratek Pharmaceuticals,
Inc.Paratek Pharmaceuticals, Inc. is a biopharmaceutical
company focused on the development and commercialization of
innovative therapies based upon its expertise in novel tetracycline
chemistry. Paratek's lead product candidate, omadacycline, is the
first in a new class of tetracyclines known
as aminomethylcyclines, with broad-spectrum activity against
Gram-positive, Gram-negative and atypical bacteria. Omadacycline is
a new, once-daily oral and intravenous broad spectrum antibiotic
being developed for use as empiric monotherapy for patients
suffering from serious community-acquired bacterial infections,
such as acute bacterial skin and skin structure infections,
community-acquired bacterial pneumonia, urinary
tract infections, and other community-acquired bacterial
infections, particularly when antibiotic resistance is of concern
to prescribing physicians. Omadacycline has been granted
Qualified Infectious Disease Product designation and Fast Track
status by the U.S. Food and Drug Administration for the target
indications.
In June 2016, Paratek announced positive efficacy
data in a Phase 3 registration study in acute bacterial skin and
skin structure infections (ABSSSI) demonstrating the efficacy,
general safety and tolerability of intravenous (IV) to once-daily
oral omadacycline compared to linezolid. In April 2017,
Paratek announced positive efficacy data in a Phase 3 registration
study in community-acquired bacterial pneumonia (CABP)
demonstrating the efficacy, general safety and tolerability of IV
to once-daily oral omadacycline compared to moxifloxacin. A Phase 3
registration study in ABSSSI comparing once-daily oral-only dosing
of omadacycline to twice-daily oral-only dosing of linezolid was
initiated in August 2016. Top-line data from this study are
expected as early as the end of June. The Company plans to
submit its new drug application (NDA) in the U.S. as early as the
first quarter of 2018 with an EMA submission later in 2018.
In addition to its Phase 3 program for
omadacycline, a Phase 1B study in uncomplicated urinary tract
infections (UTI) was initiated in May 2016 and positive top-line PK
proof-of-principle data was reported in November 2016. The Company
plans to begin enrolling patients in a proof-of-concept Phase 2
study of omadacycline in acute pyelonephritis, the most common
subset of complicated urinary tract infections, as early as
December 2017.
In October 2016, Paratek announced a research
agreement with the U.S. Department of Defense to explore
the utility of omadacycline against pathogenic agents causing
infectious diseases of public health and biodefense importance
including plague and anthrax.
Paratek's second Phase 3 product candidate,
sarecycline, is a well-tolerated, once-daily oral, narrow spectrum
tetracycline-derived antibiotic with potent anti-inflammatory
properties for the potential treatment of acne and rosacea in the
community setting. Allergan owns the U.S. rights for the
development and commercialization of sarecycline. Paratek retains
all ex-U.S. rights. Allergan and Paratek reported positive results
from two identical Phase 3 registration studies of sarecycline for
the treatment of moderate to severe acne vulgaris in March
2017. Allergan has publicly announced plans to submit an NDA
in the U.S. in the second half of 2017.
Forward Looking StatementsThis
press release contains forward-looking statements including
statements related to our overall strategy, product candidates,
clinical studies, prospects and expected results, including
statements about the timing of advancing omadacycline and otherwise
preparing for clinical studies, the timing of enrollment in our
clinical studies and of our reporting of the results of such
studies, the potential for omadacycline to serve as an empiric
monotherapy treatment option for patients suffering from ABSSSI,
CABP, UTI, and other bacterial infections when resistance is of
concern, the prospect of omadacycline providing broad-spectrum
activity, and our ability to obtain regulatory approval of
omadacycline. All statements, other than statements of historical
facts, included in this press release are forward-looking
statements, and are identified by words such as "advancing,"
"believe," "expect," "well positioned," "look forward,"
"anticipated," "continued," and other words and terms of similar
meaning. These forward-looking statements are based upon our
current expectations and involve substantial risks and
uncertainties. We may not actually achieve the plans, carry out the
intentions or meet the expectations or projections disclosed in our
forward-looking statements and you should not place undue reliance
on these forward-looking statements. Our actual results and the
timing of events could differ materially from those included in
such forward-looking statements as a result of these risks and
uncertainties. These and other risk factors are discussed under
"Risk Factors" and elsewhere in our Annual Report on Form 10-K for
the year ended December 31, 2016, and our other filings with the
Securities and Exchange Commission. We expressly disclaim any
obligation or undertaking to update or revise any forward-looking
statements contained herein.
CONTACTS:
Media Relations:
Michael Lampe
(484) 575-5040
michael@scientpr.com
Investor Relations:
Hans Vitzthum
LifeSci Advisors, LLC.
212-915-2568
Paratek Pharmaceuticals (NASDAQ:PRTK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Paratek Pharmaceuticals (NASDAQ:PRTK)
Historical Stock Chart
From Apr 2023 to Apr 2024