FDA Grants Fast Track Designation to Potential Treatment for Multiple System Atrophy

Amlenetug (Lundbeck, Deerfield, IL), a monoclonal antibody (mAb) that targets extracellular α-synuclein, was granted Fast Track Designation (FTD) by the Food and Drug Administration (FDA) for investigation as a potential treatment for multiple system atrophy (MSA). According to a statement from Lundbeck, amlenetug is designed to slow neuronal loss by preventing α-synuclein uptake and aggregation and promoting immune-mediated clearance of α-synuclein via microglia. In April 2024, amlenetug was granted Orphan Drug Designation (ODD) by the FDA for the potential treatment of MSA.

The FDA’s decision was based on data from the phase 2, randomized, double-blind, placebo-controlled AMULET clinical trial (NCT05104476), in which 61 participants with possible or probable MSA were randomized 2:1 to receive treatment with amlenetug or placebo via intravenous (IV) infusion.

• Over a 72-week treatment period, amlenetug treatment was associated with 19% slower disease progression compared with those taking placebo as measured by the Unified MSA Rating Scale (UMSARS). This was not a statistically significant difference, and the primary endpoint was not met.
• In less-impaired participants (baseline USMARS Part I ≤16), amlenetug treatment (n=30) was associated with 37% slower clinical progression vs placebo (n=12).
• A total of 45 participants elected to continue treatment during an additional 48-week open-label extension (OLE) phase.

“We are pleased that amlenetug has received Fast Track Designation for the potential treatment of Multiple System Atrophy,” said Johan Luthman, Executive Vice President and Head of Research & Development at Lundbeck. “This is a step forward in our commitment to address significant unmet needs in this devastating disease.”

Lundbeck has initiated the ongoing MASCOT phase 3 clinical trial (NCT06706622) clinical trial, which will evaluate the efficacy and safety of amlenetug administered every 4 weeks by IV infusion for over 300 participants with parkinsonian (MSA-P) or cerebellar (MSA-C) MSA subtypes. The study comprises an initial, 72-week, double-blind, placebo-controlled period followed by an OLE period wherein all participants will receive amlenetug treatment.