FDA Grants Synlogic Fast-Track Designation for Synthetic Biotic to Treat PKU

Rare Daily Staff

The U.S. Food and Drug Administration granted Synlogic Fast Track designation to its experimental therapeutics SYNB1618, a synthetic biotic to metabolize phenylalanine as a treatment for Phenylketonuria or PKU, a rare metabolic disorder.

PKU is an inborn error of metabolism caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes Phe. Phe is an essential amino acid that enters the body as a component of dietary protein and can be toxic if it accumulates in the blood and brain.

Current disease management of PKU involves strict dietary protein restriction with the consumption of Phe-free protein supplements. The only currently approved medication, Kuvan, is indicated for a subgroup of patients and does not eliminate the need for ongoing dietary management. Life-long Phe control is challenging due to the highly restrictive nature of the diet and patients typically experience worsening neurological function depending on the severity of their genetic mutation and their treatment compliance.

Synlogic leverages the tools and principles of synthetic biology to genetically engineer probiotic microbes to perform or deliver critical functions missing or damaged due to disease. SYNB1618 is a synthetic biotic medicine engineered to execute a programmed metabolic pathway designed to consume Phe and convert it into harmless metabolites, including trans-cinnamic acid in the blood, which can be further metabolized in the liver and excreted as hippurate in the urine, providing potentially important biomarkers of SYNB1618’s activity.

Synlogic has dosed the first subjects in a Phase 1/2a single and multiple dose-escalation, randomized, double-blind, placebo-controlled study of orally administered SYNB1618 in healthy adult volunteers and adult subjects with PKU, designed to evaluate safety, tolerability, kinetics, and pharmacodynamics as well as exploratory end-points associated with the ability of SYNB1618 to metabolize Phe.

The company expects to report interim data from the single ascending dose portion of the trial in 2018 and the full data in 2019.

“This represents another step in our regulatory strategy to advance the clinical development of SYNB1618 as expeditiously as possible,” said Aoife Brennan, Synlogic’s chief medical officer. “We look forward to continuing the development of SYNB1618 which has the potential to provide an improved treatment option suitable for all PKU patients.”

The FDA Fast Track program is designed to facilitate the development of important new drugs intended to treat a serious condition and to fill an unmet medical need. The designation enables early and frequent communication between the FDA and the company throughout the drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.

Through the Fast Track program, a product may be eligible for priority review at the time of a Biologic License Application and rolling review, which allows the company to submit completed sections of its application for review by the FDA, rather than waiting until the entire application is completed and submitted.

April 25, 2018
Photo: Aoife Brennan, chief medical officer of Synlogic