ROCKVILLE, Md., April 23, 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 preliminary agreement from the U.S. Food & Drug
Administration (FDA), on a proposed clinical trial synopsis for its
planned Phase 3 clinical trial for SYN-004 (ribaxamase). In
accordance with recommendations and guidance received from the FDA,
the Company expects the Phase 3 trial to include separate
co-primary endpoints designed to evaluate the efficacy and safety
of ribaxamase in a patient population being treated with a
representative selection of intravenous (IV) beta-lactam
antibiotics.
The proposed Phase 3 study discussed with the FDA comprises a
global, event-driven clinical trial with a fixed maximum number of
patients for total enrollment. The Phase 3 study proposes to
evaluate the potential efficacy and safety of ribaxamase in a
broader patient population by the inclusion of additional IV
beta-lactam antibiotics with ceftriaxone and by enrolling patients
with a variety of underlying infections. Based on a series of
collaborative discussions with the FDA, the Company expects the
primary efficacy endpoint of the proposed Phase 3 clinical trial
will be the reduction of the incidence of Clostridium
difficile infection (CDI) in the ribaxamase treatment group
relative to placebo.
The Company also announced it has preliminary agreement from the
FDA to evaluate mortality risk as the primary safety endpoint for
the trial, which will be separate from the primary efficacy
endpoint of reduction of the incidence of CDI. The designation of
efficacy and safety as separate and decoupled endpoints is critical
for clinical studies of this nature, where the underlying
population is projected to have a comparatively high incidence of
safety events that may significantly dilute the smaller number of
CDI events.
"Following recent collaborative discussions with the FDA, we
have gained clarity on several significant elements of the proposed
Phase 3 clinical program, which we believe provide a path forward
to develop ribaxamase, a product which, if approved, may address
the serious and unmet health impacts associated with
antibiotic-mediated CDI," stated Steven A.
Shallcross, Interim Chief Executive Officer and Chief
Financial Officer. "We look forward to sharing the remaining
elements of the proposed Phase 3 trial upon the completion of our
End-of-Phase 2 meeting with the FDA during the second half of 2018,
and anticipate initiating this trial during the second half of
2019."
Synthetic Biologics further announced that during the
development of the proposed Phase 3 clinical trial, the FDA
undertook an additional review of data and analysis submitted by
the Company from the previously completed ribaxamase Phase
2b clinical trial. Following FDA's
review of the additional data, it was determined that the
requirements for Breakthrough Therapy Designation were no longer
met due to the numerical imbalance in fatal adverse events observed
in the study which could not be fully evaluated due to the limited
safety database, and the study's method of statistical treatment of
patients who did not complete the study for any reason. The Company
has reached agreement with the FDA on how each of these factors
will be addressed in the Phase 3 trial by evaluating safety and
efficacy endpoints separately as described above. As a result, and
with the consent of the FDA, the Company has voluntarily withdrawn
the Breakthrough Therapy Designation for the ribaxamase program.
The FDA stated in their official response to the Company that they
remain committed to working with Synthetic Biologics on the
development of the ribaxamase program, and the withdrawal of
Breakthrough Therapy Designation will not affect interactions
between the two parties.
"We are grateful to have received guidance and continued support
from the FDA as part of ribaxamase's development and remain
encouraged that a robust, controlled, and well-designed clinical
trial may provide sufficient efficacy and safety data to support a
pathway towards marketing approval for ribaxamase," concluded
Shallcross.
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 poised for Phase 3 development 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 for the prevention of 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.
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.
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 expectations that the Phase 3 clinical trial for SYN-004
will include separate co-primary endpoints, comprise a
global, event-driven clinical trial with a fixed maximum number of
patients for total enrollment, evaluate the potential
efficacy and safety of ribaxamase in a broader patient population
by the inclusion of additional IV beta-lactam antibiotics with
ceftriaxone and by enrolling patients with a variety of underlying
infections, have as the primary efficacy endpoint the reduction of
the incidence of Clostridium difficile infection (CDI) in the
ribaxamase treatment group relative to placebo and evaluate
mortality risk as the primary safety endpoint, which will be
separate from the primary efficacy endpoint; the belief that the
proposed Phase 3 clinical program will provide a path forward to
develop ribaxamase which if approved, may address the serious and
unmet health impacts associated with antibiotic-mediated CDI; the
anticipated timing of the initiation of the Phase 3 clinical trial
during the second half of 2019 following the end of Phase 2
meeting, which is anticipated to be during the second half of 2018,
the belief that a robust, controlled, and well-designed clinical
trial may provide sufficient efficacy and safety data to support a
pathway towards marketing approval for ribaxamase, 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 implement the Phase 3 program as a global, event-driven clinical
trial, Synthetic Biologics' ability to initiate the Phase 3
clinical program in the second half of 2019 following an end of
Phase 2 meeting with the FDA during the second half of 2018,
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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