Progressive Supranuclear Palsy Treatment, ASN120290, Gets Orphan Drug Designation

This afternoon, July 18, 2018, the US Food and Drug Administration (FDA) granted an orphan drug designation to Asceneuron SA for its product, ASN120290 (formerly known as ASN-561), for the treatment of progressive supranuclear palsy (PSP), a sporadic and rare neurodegenerative disorder characterized by the accumulation of aggregates of the tau protein in the brain.

ASN120290 is a selective O-GlcNAcase enzyme inhibitor believed to have the ability to substantially reduce the build-up of toxic aggregates of tau into neurofibrillary tangles. Historically, neurofibrillary tangles have been recorded as a key driver of neurodegeneration and clinical symptoms in the majority of dementia cases.

"PSP is a rare neurological condition for which there is currently no treatment available,” commented Dirk Beher, chief executive officer and a founder of Asceneuron, in a recent statement. “The granting of Orphan Drug Designation for ASN120290 by the FDA is an important milestone for the team and the company. It strengthens our commitment to serving this important unmet medical need and bringing this molecule to patients."

In preclinical studies, ASN120290 showed therapeutic potential with its demonstrated ability to substantially reduce the build-up of toxic aggregates of tau into neurofibrillary tangles in mice. Specifically, ASN120290 increased O-GlcNAcated tau 12-fold. After 3.5 months of treatment, the mice also experienced increases in tau O-GlcNAcylation with 100 mg/kg. A dose of 30 mg/kg was not as effective.

Overall, mice treated with higher doses of ASN120290 were found to have less phosphorylated tau, to have developed 40% fewer paired helical filaments in cortex, and to have formed 80% fewer neurofibrillary tangles.

ASN120290 was also recently assessed in a completed a randomized, double-blind, placebo-controlled phase 1 study for safety and efficacy of single and multiple doses among healthy young and elderly volunteers. Data from the study will be presented at the Alzheimer's Association International Conference (AAIC) held this year in Chicago, Illinois, from July 22 to 26.