ROCKVILLE, Md., Nov. 21, 2018 /PRNewswire/ -- Synthetic
Biologics, Inc. (NYSE American: SYN), a late-stage clinical company
developing therapeutics designed to preserve the microbiome to
protect and restore the health of patients, today announced that it
has successfully completed an End-of-Phase 2 meeting with the U.S.
Food and Drug Administration (FDA) to discuss development of
SYN-004 (ribaxamase) for the prevention of antibiotic-mediated
Clostridium difficile infection (CDI). Pursuant to the
meeting, the FDA has proposed criteria for Phase 3 clinical
efficacy and safety which, if achieved, may support submission for
marketing approval of ribaxamase on the basis of a single Phase 3
clinical trial. Final agreement on these criteria is contingent on
FDA evaluation of a detailed Phase 3 clinical trial protocol.
"We are very pleased with the productive advice we have received
from the FDA during our recent End-of-Phase 2 meeting," said
Steven A. Shallcross, Interim Chief
Executive Officer and Chief Financial Officer. "Having a clear path
forward in the form of a Phase 3 clinical program for ribaxamase is
an exciting and important milestone for our company and should be
highly beneficial in our ongoing strategic partnering
discussions."
Synthetic Biologics, in consultation with the FDA, has confirmed
the key elements of the Phase 3 clinical program to support a
marketing application for ribaxamase, the Company's first-in-class
oral enzyme designed to degrade certain intravenous (IV)
beta-lactam antibiotics within the gastrointestinal (GI) tract to
prevent microbiome damage, Clostridium difficile infection
(CDI), overgrowth of pathogenic organisms and the emergence of
antimicrobial resistance (AMR). The proposed ribaxamase Phase 3
clinical program will entail a single, global, event-driven
clinical trial with a fixed maximum number of patients for total
enrollment and will evaluate the potential efficacy and safety of
ribaxamase in a broad patient population by enrolling patients with
a variety of underlying infections treated with a range of IV
beta-lactam antibiotics.
The primary efficacy endpoint of the Phase 3 clinical trial will
be the reduction in the incidence of CDI at one month after the
last drug dose in the ribaxamase treatment group versus placebo.
The Company also confirmed that the FDA agreed to a primary safety
endpoint of noninferiority in mortality between the ribaxamase
treatment group versus placebo at 3 months post-randomization. The
designation of efficacy and safety as separate and decoupled
endpoints is critical for clinical studies of this nature, where
the underlying population, regardless of treatment group, is
projected to have a comparatively high incidence of safety events
that may significantly dilute the smaller number of CDI events.
Synthetic Biologics anticipates initiating the Phase 3 clinical
program after securing additional potential financing via a
strategic partnership. In parallel, the Company is evaluating
opportunities to advance ribaxamase through the pursuit of a more
focused clinical indication in a specialty patient population with
multiple potential disease endpoints associated with IV
beta-lactam-induced gut microbiome damage. Such a dual approach is
designed to advance ribaxamase in areas of clear unmet medical need
while also expanding upon ribaxamase's current data set and
providing further validation for use in the broader indication for
the prevention of CDI.
About Clostridium difficile infection
Clostridium difficile infection (CDI) is a leading
hospital acquired infection in the U.S., with more than
453,0001 patients diagnosed annually. CDI results in
approximately 29,000 deaths1, $5.42 billion in additional healthcare
costs, as well as significant and sometimes prolonged illness.
Approximately 1 in 5 CDI patients experience at least one CDI
recurrence3.
About SYN-004 (ribaxamase) and the Phase 2b proof-of-concept clinical trial
SYN-004 (ribaxamase) is a first-in-class oral enzyme
prophylactic therapy designed to degrade certain IV beta-lactam
antibiotics within the GI tract and maintain the natural balance of
the gut microbiome for the prevention of Clostridium
difficile infection (CDI), overgrowth of pathogenic organisms
and the emergence of antimicrobial resistance (AMR). A previously
completed randomized, double-blind, placebo-controlled Phase
2b proof-of-concept clinical trial of
412 patients met its primary endpoint of significantly reducing
C. difficile infection (CDI). Preliminary analysis of the
data indicated seven confirmed cases of CDI in the placebo group
compared to two cases in the ribaxamase treatment group. Patients
receiving ribaxamase achieved a 71.4% relative risk reduction
(p-value=0.045) in CDI rates compared to patients receiving
placebo.
About Synthetic Biologics, Inc.
Synthetic Biologics, Inc. (NYSE American: SYN) is a late-stage
clinical company developing therapeutics that preserve the
microbiome to protect and restore the health of patients. The
Company's lead candidates are: (1) SYN-004 (ribaxamase) which is
designed to protect the gut microbiome from the effects of certain
commonly used intravenous (IV) beta-lactam antibiotics to prevent
microbiome damage, C. difficile infection (CDI), overgrowth
of pathogenic organisms and the emergence of antimicrobial
resistance (AMR), and (2) SYN-010 which is intended to reduce the
impact of methane producing organisms in the gut microbiome to
treat an underlying cause of irritable bowel syndrome with
constipation (IBS-C). The Company's preclinical pursuits include an
oral formulation of the enzyme intestinal alkaline phosphatase
(IAP) to treat both local GI and systemic diseases as well as
monoclonal antibody therapies for the prevention and treatment of
pertussis, and novel discovery stage biotherapeutics for the
treatment of phenylketonuria (PKU). For more information, please
visit Synthetic Biologics' website at
www.syntheticbiologics.com.
This release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. In
some cases forward-looking statements can be identified by
terminology such as "may," "should," "potential," "continue,"
"expects," "anticipates," "intends," "plans," "believes,"
"estimates," and similar expressions, and includes statements
regarding a single Phase 3 clinical trial being sufficient for
approval for prevention of antibiotic-mediated clostridium
difficile infection, the achievement of the FDA proposed criteria
for Phase 3 clinical efficacy and safety supporting submission for
marketing approval of SYN-004 (ribaxamase) on the basis of a single
Phase 3 clinical trial, having a clear path forward in the form of
a Phase 3 clinical program for SYN-004 being highly beneficial in
our ongoing strategic partnering discussions, the anticipated
initiation of the Phase 3 clinical program after securing
additional potential financing via a strategic partnership,
development of SYN-004 (ribaxamase) as potentially the first
intervention designed to specifically to prevent antibiotic damage
to the microbiome, opportunities that would enable the
advancement of SYN-004 through the pursuit of a more focused
clinical indication in a specialty patient population with multiple
potential disease endpoints associated with IV beta-lactam-induced
gut microbiome damage and the potential benefits of SYN-004
and SYN-010. These forward-looking statements are based on
management's expectations and assumptions as of the date of this
press release and are subject to a number of risks and
uncertainties, many of which are difficult to predict that could
cause actual results to differ materially from current expectations
and assumptions from those set forth or implied by any
forward-looking statements. Important factors that could cause
actual results to differ materially from current expectations
include, among others, Synthetic Biologics' ability to design a
Phase 3 trial with the co-primary endpoints and receive FDA
approval for such design, Synthetic Biologics' ability to initiate
the Phase 3 clinical program after securing additional financing
via a strategic partnership, Synthetic Biologics' ability to
establish a path forward to develop ribaxamase and conduct a
robust, controlled and well-designed clinical trial that may
provide sufficient efficacy and safety data to support a pathway
towards marketing approval for ribaxamase, Synthetic Biologics'
ability to regain compliance with the continued listing standards
of the NYSE American by September 2,
2019, Synthetic Biologics' ability to comply with other
continued listing requirements of the NYSE American, the ability of
its product candidates to demonstrate safety and
effectiveness, as well as results that are consistent with prior
results, Synthetic Biologics' clinical trials continuing enrollment
as expected, a failure to receive the necessary regulatory
approvals for commercialization of Synthetic Biologics'
therapeutics, including approval of proposed trial designs, a
failure of Synthetic Biologics' clinical trials, and those
conducted by investigators, for SYN-004 and SYN-010 to be commenced
or completed on time or to achieve desired results and benefits, a
failure of Synthetic Biologics' clinical trials to continue
enrollment as expected or receive anticipated funding, a failure of
Synthetic Biologics to successfully develop, market or sell its
products, Synthetic Biologics' inability to maintain its material
licensing agreements, or a failure by Synthetic Biologics or its
strategic partners to successfully commercialize products,
Synthetic Biologics' ability to achieve acceptance of its
product candidates in the marketplace and the successful
development, marketing or sale of Synthetic Biologics' products by
competitors that render Synthetic Biologics' products obsolete or
non-competitive, the continued maintenance and growth of Synthetic
Biologics' patent estate, Synthetic Biologics becoming and
remaining profitable, Synthetic Biologics' ability
to obtain or maintain the capital or grants necessary to fund its
research and development activities, a loss of any of Synthetic
Biologics' key scientists or management
personnel and other factors described in Synthetic
Biologics' most recent Form 10-K and its other filings with the
SEC, including subsequent periodic reports on Forms 10-Q and 8-K.
The information in this release is provided only as of the date of
this release, and Synthetic Biologics undertakes no obligation to
update any forward-looking statements contained in this release on
account of new information, future events, or otherwise, except as
required by law.
References:
1. Lessa, F.C., Winsto., & McDonald, L.C; (2015). Emerging
Infections Program C. difficile Surveillance Team.
Burden of Clostridium difficile infection in the United
States. New England Journal of Medicine. Retrieved from
http://www.nejm.org/doi/full/10.1056/NEJMc1505190#t=article (Last
accessed August 2017).
2. Desai K, Gupta SB, Dubberke ER, Prabhu VS, Browne C, Mast TC.
Epidemiological and economic burden of Clostridium
difficile in the United
States: estimates from a modeling approach. BMC
Infectious Diseases. 2016;16:303.
doi:10.1186/s12879-016-1610-3.
3. Kleef, E van et al. "Excess length of stay and mortality due to
Clostridium difficile infection: a multi-state modelling
approach." The Journal of hospital infection 88 4
(2014): 213-7. DOI: 10.1016/j.jhin.2014.08.008
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