Sanfilippo syndrome type A is caused by mutations in the gene that provides instructions to make the enzyme N-sulfoglucosamine sulfohydrolase (SGSH).
This leads to the accumulation of a complex sugar molecule called heparan sulfate within the brain and other tissues, leading to progressive intellectual disability and loss of previously acquired skills.
AGT‑184 is an experimental enzyme replacement therapy (ERT) under development by ArmaGen. It consists of an SGSH enzyme bound to a human anti-insulin receptor antibody.
Using this antibody enables the compound to cross the blood-brain barrier (BBB) — a semipermeable membrane that protects the brain — in a “Trojan horse” manner. This ability to reach the brain is essential for any effective therapy for Sanfilippo syndrome type A.
Preclinical work showed AGT-184 has a similar enzyme activity as the normal SGSH enzyme. In a mouse model of Sanfilippo syndrome type A, a six-week long, three times weekly treatment with a version of AGT-184 reduced the levels of heparan sulfate by 70% in the brain and 85% in the liver. The mice also revealed improved motor activity. No adverse events were detected.
These results provide evidence that AGT-184 can reach the brain and is active in peripheral organs.
“We are very pleased to receive FDA orphan drug designation for AGT-184, as this designation is an important regulatory milestone for the Company as we work to develop a potential treatment option for patients suffering from this rare and life-threatening disease,” Mathias Schmidt, PhD, ArmaGen’s CEO, said in a press release.
Schmidt said the FDA’s decision comes at a time when ArmaGen is preparing to advance the development of other potential therapies based on the same BBB platform as AGT-184.
ArmaGen is currently planning to file an investigational new drug application (IND) to the FDA in late 2019 for AGT-184. FDA review of an IND ensures that the drug is safe for testing in humans and that clinical trials will not put study participants at unreasonable risk.
Orphan drug status is granted to investigational therapies designed to treat conditions affecting fewer than 200,000 people in the U.S., or that will likely not make a profit because there are too few patients who have the disease.
This designation provides various incentives, including tax credits for clinical tests and fee waivers, and it may confer seven-year market exclusivity if the therapy is approved.