Regulatory authorities in Spain and Poland have approved the expansion of BioArctic AB's Phase 2a EXIST trial to include patients with Multiple System Atrophy (MSA), a rare and fatal neurodegenerative disorder. The trial will now evaluate the alpha-synuclein antibody exidavnemab in both Parkinson's disease and MSA patients.
The EXIST (EXIdavnemab Synucleinopathy Trial) study was originally designed to assess the safety and tolerability of exidavnemab in patients with Parkinson's disease. With this substantial protocol modification, researchers will now recruit an additional cohort of 12 MSA patients alongside the 24 participants with mild to moderate Parkinson's disease.
"This expansion represents a significant opportunity to address an area of critical unmet need," said Charlotte af Klercker, Senior Director of Sustainability and Communications at BioArctic. "MSA patients currently have no disease-modifying treatment options available to them."
Understanding Multiple System Atrophy
MSA is characterized by pathological alpha-synuclein aggregation that progressively damages nerve cells in the brain. The disease affects multiple neurological systems, impairing balance, movement, and autonomic functions including breathing, digestion, and bladder control.
The prognosis for MSA patients is particularly poor, with survival typically limited to 6-10 years after symptom onset. Few patients survive beyond 15 years. Classified as a rare disease, MSA affects fewer than 42,000 people in the United States.
Dr. Anders Martin-Löf, CFO of BioArctic, emphasized the disease's rapid progression: "The devastating nature of MSA and the complete lack of treatments that can slow its course make this an urgent area for clinical research."
Trial Design and Objectives
The randomized, double-blinded, placebo-controlled study is being conducted at clinical sites in Spain and Poland. Beyond the primary endpoints of safety and tolerability, the trial will evaluate a comprehensive range of biomarkers in plasma and cerebrospinal fluid (CSF), as well as through digital measurements.
This biomarker analysis may provide crucial insights into the drug's mechanism of action and potential efficacy signals. The inclusion of digital measurements represents an innovative approach to capturing subtle changes in neurological function that might not be detected through traditional clinical assessments.
Exidavnemab's Mechanism and Potential
Exidavnemab is a monoclonal antibody specifically designed to target and eliminate aggregated forms of alpha-synuclein, including oligomers, protofibrils, and fibrillar forms. These protein aggregates are implicated in the pathogenesis of several neurodegenerative disorders, including both Parkinson's disease and MSA.
The antibody's mechanism of action involves promoting the clearance of these toxic protein aggregates, potentially reducing their spread and harmful effects on neuronal function. By preserving cellular function and survival, exidavnemab aims to slow disease progression.
In March 2025, the U.S. Food and Drug Administration's Office of Orphan Products Development granted orphan drug designation to exidavnemab for the treatment of MSA, highlighting the significant unmet need in this patient population.
Significance for Alpha-Synucleinopathies
The EXIST trial, which has been ongoing since 2024, represents an important step toward a proof-of-concept study that would focus on the efficacy of exidavnemab. If successful, this approach could potentially address multiple neurodegenerative conditions characterized by alpha-synuclein aggregation.
BioArctic has established expertise in developing treatments for neurodegenerative diseases. The company is the originator of Leqembi® (lecanemab), the first drug proven to slow the progression of Alzheimer's disease and reduce cognitive impairment in early stages of the condition. Leqembi was developed in partnership with Eisai.
Looking to the Future
While the current study focuses on safety and tolerability, the inclusion of biomarker assessments may provide early indications of the drug's potential efficacy. However, BioArctic has emphasized that this release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety.
The company acknowledges that there is no guarantee that exidavnemab will successfully complete clinical development or gain health authority approval. Nevertheless, the expansion of the trial to include MSA patients represents an important advancement in the field of synucleinopathy research and offers hope for patients with limited therapeutic options.
The EXIST trial's results will be closely watched by clinicians, researchers, and patients affected by these devastating neurodegenerative conditions.
