H. Lundbeck A/S presented key pipeline data for amlenetug, an investigational monoclonal antibody targeting α-synuclein, at the 2025 International MSA Congress in Boston. The presentations included results from the completed phase II AMULET trial and new natural history data from the TALISMAN study, providing crucial insights into multiple system atrophy (MSA) progression as the company prepares for phase III development.
Phase II AMULET Trial Results
The AMULET trial (NCT05104476) was a phase II, randomized, double-blind, placebo-controlled clinical trial evaluating amlenetug as a potential treatment for patients with MSA. Patients were randomized 2:1 to receive either amlenetug or placebo and treated for 48 to 72 weeks, followed by an ongoing 96-week open-label extension period offering all participants treatment with amlenetug.
The primary objective was to evaluate the efficacy of amlenetug on clinical progression in patients with MSA, aiming to demonstrate slowing in clinical progression in the active treatment arm compared to placebo on a 5% significance level evaluated one-sided, as well as assess safety and tolerability. Secondary objectives included evaluation of amlenetug's effects on patient functioning, disease severity and other aspects of MSA. Amlenetug was delivered as an intravenous infusion every four weeks.
Natural History Study Provides Critical Insights
Lundbeck also presented new insights from the TALISMAN study, a natural history investigation examining MSA progression. According to Johan Luthman, EVP and Head of Research & Development at Lundbeck, "MSA is a debilitating disease with a poor prognosis and a significant unmet medical need, however relatively little is known about its progression and natural history, particularly at the early stage."
Studying disease progression and survival is essential to understand the natural history of MSA, however currently there is limited data available. The TALISMAN study helps to better understand how the disease develops over time, particularly in the early MSA population, and support phase III drug development.
Patient-Centered Approach Informs Phase III Design
Lundbeck presented insights from patients who participated in the completed phase II AMULET trial. These insights highlight the burden of the disease, both for people living with MSA and their care partners. The perspectives from patient exit-interviews have informed the design of the phase III MASCOT trial, demonstrating Lundbeck's continued commitment to elevating the patients' voice in the R&D process and optimizing clinical trial design around patient needs.
Advancing to Phase III with MASCOT Trial
The data presentation comes as Lundbeck prepares for the phase III MASCOT trial (NCT06706622), an interventional, randomized, double-blind, parallel-group, placebo-controlled study with an optional open-label extension. The trial will be conducted in North America, Europe, Asia and Australia.
The MASCOT trial comprises two parts: a double-blind period where participants are 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 enrolled in the trial are offered treatment with amlenetug. The aim is to evaluate the efficacy, safety, and tolerability of amlenetug in patients with MSA, with amlenetug delivered as an intravenous infusion every four weeks.
About Amlenetug and MSA
Amlenetug is a human monoclonal antibody that recognizes and binds to all major forms of extracellular α-synuclein, intended to prevent uptake and inhibit seeding of aggregation. The drug is being developed by Lundbeck under a joint research and licensing agreement between Lundbeck and Genmab A/S.
MSA is a rare, rapidly progressing neurodegenerative disease for which there are currently no approved therapies. Luthman emphasized the importance of the patient-level data, stating it is "critical to guiding our R&D efforts as we move into Phase III trials" and expressed the company's commitment to "discussing the impact of this data on future horizons in MSA management."
