Lundbeck's investigational drug, amlenetug, a human monoclonal antibody targeting multiple system atrophy (MSA), has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). This designation aims to expedite the development and review process for drugs treating serious conditions and addressing unmet medical needs, offering hope for patients with this rare and debilitating neurodegenerative disorder. The decision is based on encouraging outcomes from the Phase II AMULET trial and supports the ongoing Phase III MASCOT trial.
Mechanism of Action
Amlenetug is designed to bind to all major forms of extracellular α-synuclein, preventing its uptake and inhibiting the seeding of aggregation. The active Fc region of the antibody may also promote immune-mediated clearance of α-synuclein via microglia-mediated uptake. This dual mechanism aims to reduce the buildup of α-synuclein, thought to be responsible for damaging areas of the brain that control balance, movement, and autonomic functions in MSA patients.
Clinical Trial Data
The Fast Track Designation was supported by data from the Phase II AMULET trial (NCT05104476), a randomized, double-blind, placebo-controlled study involving 61 patients with MSA. While the trial did not meet its primary endpoint of statistically significant slowing of disease progression, it showed a consistent trend towards amlenetug slowing clinical progression in MSA patients. Specifically, a 19% slowing of clinical progression was observed as measured by the Unified Multiple System Atrophy Rating Scale (UMSARS) total score versus placebo.
Johan Luthman, EVP and Head of Research & Development at Lundbeck, stated, "We are pleased that amlenetug has received Fast Track Designation for the potential treatment of Multiple System Atrophy. This is a step forward in our commitment to address significant unmet needs in this devastating disease."
MASCOT Phase III Trial
Building on these results, Lundbeck has initiated the Phase III MASCOT trial (NCT06706622) to further evaluate the efficacy, safety, and tolerability of amlenetug in a larger patient population. MASCOT is a global, interventional, randomized, double-blind, parallel-group, placebo-controlled, optional open-label extension trial conducted in North America, Europe, and Asia. Participants will be randomized to receive either high or low doses of amlenetug or placebo for 72 weeks, followed by an open-label extension period where all participants can receive amlenetug.
Amlenetug will be administered as an intravenous infusion every four weeks. The trial aims to evaluate the efficacy, safety, and tolerability of amlenetug in patients with MSA.
Prior Designations and Strategic Significance
In addition to the Fast Track Designation, amlenetug has received Orphan Drug Designation from the FDA and the European Medicines Agency (EMA), as well as SAKIGAKE designation from Japan’s Ministry of Health, Labour and Welfare. These designations provide additional incentives and support for the development of treatments for rare diseases.
Lundbeck's commitment to the neuro-rare disease sector was further solidified by its acquisition of Longboard Pharmaceuticals in December 2024.
About Multiple System Atrophy
MSA is a rare, rapidly progressive neurodegenerative disorder affecting the brain's nerve cells responsible for motor control and autonomic functions. Symptoms typically begin between 55 and 60 years of age, with patients surviving approximately 6 to 9 years after onset. There is currently no cure for MSA, and treatments are limited to managing symptoms. MSA affects fewer than 200,000 people in the U.S. at the time of designation.
