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.
SOURCE Synthetic Biologics, Inc.