PKU is an inborn error of metabolism (IEM) caused by a mutation in the gene that breaks down the amino acid phenylalanine (Phe).
Phe accumulation in the blood and brain can lead to neurocognitive abnormalities and treatment currently requires severe dietary protein restriction.
SYNB1618, an orally administered medicine, is designed to complement the missing function in patients with PKU by providing alternative metabolic pathways to consume Phe. Synlogic plans to file an investigational new drug application (IND) with the FDA for SYNB1618 for the potential treatment of PKU in early 2018.
“We believe our Synthetic Biotic medicines could transform the treatment of PKU,” said Aoife Brennan, M.B., B.Ch., Synlogic’s chief medical officer.
“Consequently, we were pleased to receive the FDA’s orphan drug designation which validates our approach and represents an important step toward achieving our goal of bringing novel treatments to the patients and families affected by this challenging disease.”
The FDA’s Orphan Drug Program offers orphan status to drugs and biologics that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the U.S. The designation provides development and commercial incentives for designated compounds and medicines, including eligibility for a seven-year period of market exclusivity in the U.S. after product approval, FDA assistance in clinical trial design and an exemption from FDA user fees.
Phe is an essential amino acid that enters the body as a component of dietary protein and can be toxic if its levels accumulate in the blood and brain. PKU is caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes Phe. 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.
PKU is diagnosed at birth, and the National PKU Alliance estimates that there are currently 16,500 people living with the disorder in the U.S.