Potential PKU Treatment Receives FDA Fast Track Designation

Potential PKU Treatment Receives FDA Fast Track Designation

By Krista Rossi

This morning, Synlogic announced that SYNB1618, received the US Food and Drug Administration’s (FDA) Fast Track designation for the treatment of phenylketonuria (PKU). Synlogic’s president and chief executive officer, JC Gutiérrez-Ramos, PhD, made Rare Disease Report aware that the drug had recently entered the clinic in an exclusive interview last week.

SYNB1618 is designed to carry out a programmed metabolic pathway engineered to consume phenylalanine (Phe)and convert it into harmless metabolites. Trans-cinnamic acid in the blood, which can be further metabolized in the liver and excreted as hippurate in the urine, includes such harmless metabolites. This process provides potentially important biomarkers of SYNB1618’s activity.¹

PKU is a genetic disorder that includes a decreased metabolism and the accumulation of acid Phe, an amino acid, which, when not properly managed, can result in seizures and cognitive impairment.

The first subjects were recently dosed a Phase 1/2a clinical trial of SYNB1618 to assess the drug’s safety, tolerability, and exploratory endpoints. Both healthy volunteers and patients with PKU participated, and the interim data is expected in 2018.

Part 1 of the study will evaluate a single-ascending dose over 4 days in healthy volunteers in an inpatient setting. In order to identify the maximum tolerated dose within the single dose range, participants will be tested in up to 6 dose cohorts (3 treated : 1 placebo). Part 2 of the study will assess a multiple-ascending dose over 10 days in healthy volunteers in an inpatient setting. Participants will be tested in up to 4 cohorts (6 treated : 2 placebo) and treated at doses that will not exceed the maximum tolerated dose that will have been previously established by the single-ascending dose portion of the study.²

Aoife Brennan, MB, BCh, Synlogic’s chief medical officer, expressed his optimism regarding the drug’s potential. “The FDA’s decision to grant Fast Track status to our SYNB1618 program, which has already received Orphan Drug Designation, underscores the high unmet medical need among patients with PKU. This represents another step in our regulatory strategy to advance the clinical development of SYNB1618 as expeditiously as possible. We look forward to continuing the development of SYNB1618 which has the potential to provide an improved treatment option suitable for all PKU patients.”

In addition, with Fast Track designation, SYNB1618 may qualify for priority review at the time of Biologic License Application (BLA) and rolling review. Such qualifications can allow the submissions of completed sections to the FDA for review and bypass waiting until the complete application is submitted.

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References:

1. Synlogic Receives Fast-Track Designation for SYNB1618, a Synthetic Biotic medicine for the Treatment of Phenylketonuria. https://www.businesswire.com/news/home/20180425005307/en/Synlogic-Receives-Fast-Track-Designation-SYNB1618-Synthetic-Biotic%E2%84%A2. Accessed April 25, 2018.

2. Can Probiotic Bacteria Treat PKU? Potential Therapy Enters the Clinic. https://www.mdmag.com/medical-news/synb1618-pku-enters-the-clinic. Accessed April 25, 2018.