Lundbeck A/S announced new data from the TALISMAN study and additional findings from the AMULET trial of amlenetug (Lu AF82422) in Multiple System Atrophy (MSA) at the International Congress of Parkinson's Disease and Movement Disorders (MDS) in Philadelphia. The TALISMAN study provides insights into the progression of MSA in a Chinese population, while the AMULET trial demonstrates promising results for amlenetug in slowing clinical progression.
TALISMAN Study: Understanding MSA Progression in China
The TALISMAN study was a prospective, observational, multicenter cohort study conducted across eight sites in China, involving 89 participants with early-stage MSA. Approximately 52% of participants had MSA-C (cerebellar type), and 48% had MSA-P (parkinsonian type). The study aimed to understand the epidemiology of early-stage MSA over a relatively long observation period in the Chinese population. The mean rate of Total Unified Multiple System Atrophy Rating Scale (UMSARS) progression was 1.27 ± 0.13 [95%CI: 1.01, 1.53] points per month. Participants showed a progression of 0.64 ± 0.06 [0.51, 0.76] points/month on UMSARS Part I and 0.62 ± 0.07 [0.47, 0.77] points/month on UMSARS Part II.
AMULET Trial: Amlenetug Shows Promise in Slowing MSA Progression
The AMULET trial was a Phase II, double-blind, randomized, placebo-controlled trial investigating the safety and efficacy of monthly intravenous infusions of amlenetug (Lu AF82422) in patients with MSA (NCT05104476). The trial included 61 participants, with 40 receiving amlenetug and 21 receiving placebo. While the primary endpoint showed a non-statistically significant 19% slowing of clinical progression measured by UMSARS total score in the amlenetug group versus placebo, slope analysis of modified UMSARS (mUMSARS), UMSARS Part I, and UMSARS Part II showed a consistent slowing in clinical progression of 27%, 22%, and 17%, respectively. A post-hoc analysis of a less impaired subgroup demonstrated a 42% slowing of progression in amlenetug-treated patients. Additionally, a trend towards smaller regional MRI volumetric reduction was observed in the amlenetug group compared to placebo. Amlenetug was generally well-tolerated.
Amlenetug (Lu AF82422): Targeting Alpha-Synuclein in MSA
Amlenetug (Lu AF82422) is a human monoclonal antibody (mAb) designed to recognize and bind to all major forms of extracellular α-synuclein, potentially preventing its uptake and inhibiting the seeding of aggregation. The antibody has an active Fc region, which may enhance immune-mediated clearance of α-synuclein/mAb complexes through microglia-mediated uptake. Lundbeck is developing amlenetug under a joint research and licensing agreement with Genmab A/S.
Next Steps: Phase III Trial Planned for 2025
Based on the encouraging outcomes from the AMULET trial, Lundbeck is on track to initiate a Phase III trial of amlenetug at the beginning of 2025. This represents a significant step forward in addressing the unmet needs of patients with MSA, a rapidly progressing and debilitating neurodegenerative disorder.
Multiple System Atrophy: A Devastating Condition
Multiple System Atrophy (MSA) is a rare and rapidly progressing neurodegenerative condition characterized by damage to nerve cells in the brain. Symptoms typically manifest between 55 and 60 years of age, with patients surviving for approximately 6 to 9 years after symptom onset. The disease is marked by an abnormal build-up of the protein alpha-synuclein, leading to impaired balance, movement, and autonomic functions. Currently, there is no cure for MSA, and treatments to slow its progression are lacking.
