Breakthrough Clinical Results
Alterity Therapeutics announced positive topline data from the open-label Phase 2 clinical trial (ATH434-202) of ATH434 in patients with multiple system atrophy (MSA). The trial, which enrolled patients with more advanced disease than a previous Phase 2 trial, showed ATH434 demonstrated clinical benefit on the Modified Unified MSA Rating Scale and global measures of neurological symptoms. Neuroimaging biomarkers indicated target engagement and slowed brain atrophy. ATH434 was well-tolerated. These results are consistent with the earlier Phase 2 trial and support further development of ATH434 for MSA.
Key Highlights
- ATH434 showed clinical benefit in advanced MSA patients.
- Neuroimaging biomarkers demonstrated target engagement and slowed brain atrophy.
- ATH434 was well-tolerated with a favorable safety profile.
- Data support advancement of ATH434 in MSA.
Incidence and Prevalence
Latest Estimates of Multiple System Atrophy Incidence and Prevalence
US Prevalence and Incidence (2023)
A 2023 US study provided the most recent epidemiological data on Multiple System Atrophy (MSA), estimating the crude prevalence at 7.2 per 100,000 persons in 2021. After standardization, the age-adjusted prevalence was 12.4 per 100,000, which translates to approximately 41,133 persons in the 2021 US population. For individuals with at least two MSA claims, the figures were lower: crude prevalence of 3.1 and age-adjusted prevalence of 5.7 per 100,000 persons.
The same study reported that the crude cumulative incidence of MSA for individuals aged 30 years and older was 9.8 per 100,000 persons in 2021. When age-adjusted to the 2021 US population, the estimated cumulative incidence rose to 14.2 per 100,000.
Japanese Epidemiology
A 2016 epidemiological study from Hokkaido, Japan analyzed data from 839 MSA patients. In this population, 49% were male, and the mean onset age was 62.1 ± 10.4 years. The study found that patients with cerebellar ataxia onset symptoms had better prognosis than those with parkinsonism or autonomic failure onset. Additionally, higher onset age correlated with poor prognosis.
Another finding from Japan indicates that MSA accounts for more than 40% of spinocerebellar ataxias in the country.
Pan-American Data
A 2015 Pan-American multicentre cohort study reported the mean age at onset of MSA was 65 ± 10 years. In this population, 67.29% of individuals had the MSA-P variant with a mean onset age of 61.47 ± 10.28 years. For MSA-C patients, the mean onset age was 57.44 ± 10.58 years.
Interestingly, MSA-C was more prevalent in Non-Caucasian populations (50 Mestizo and 2 Asian patients) than in Caucasians (51.92% vs. 20.79%, p = 0.0001). The study noted that epidemiological data appears similar to other Western international series, except for the MSA-C phenotype predominance in Non-Caucasians, specifically the Mestizo population.
Associated Conditions
A 2021 study of 658 MSA patients with a mean disease duration of 2.55 ± 1.47 years found that cognitive impairment was present in 45.0% of patients. Among these patients, hypertension was recorded in 20.2%, diabetes mellitus in 10.3%, hyperlipidemia in 10.2%, smoking in 41.2%, drinking in 34.8%, and obesity in 9.6%.
While these studies provide valuable regional insights into MSA epidemiology, comprehensive global incidence and prevalence rates are not available in the most recent literature. Recent studies (2023-2024) have focused more on biomarkers and diagnostic tools rather than global epidemiological data.
Economic Burden
Economic Burden of Multiple System Atrophy in Europe
European Economic Impact
According to a 2011 Danish study, the annual mean excess health-related cost for patients with Multiple System Atrophy (MSA) was €9,771 (equivalent to $13,491/£8,332) per patient. Additionally, MSA patients received an annual mean excess social transfer income of €844 (equivalent to £719/$1,165).
This comprehensive study compared 647 MSA patients with 2,588 control cases matched for age, gender, civil status, and geographic location. The research revealed that MSA patients had significantly higher rates of health-related contact and medication use, resulting in a higher socioeconomic cost.
The employment impact was substantial, with MSA patients showing very low employment rates. Those who remained employed had lower income levels than employed control subjects. Importantly, these employment and health-related consequences could be identified up to 8 years before the first diagnosis and increased with disease advancement.
Recent Epidemiological Data from Spain
A 2024 Spanish study reported the first population-based epidemiological study on MSA in Spain, finding a point prevalence of 2.43/100,000 inhabitants in December 2021. The study observed a crude average annual incidence rate of 0.49/100,000 person-years, with the highest incidence occurring in the 60-69 years age group.
The median age at symptom onset was 65 years (range 47-76), and the median time to diagnosis was 36 months. Median survival time from clinical onset was 7 years, with age of onset above 70 years and autonomic onset associated with reduced survival.
Socioeconomic Impact
MSA, along with Parkinson's disease, has major socioeconomic consequences for both patients and society. The health effects of MSA are present for up to more than 8 years before a diagnosis, indicating a prolonged period of economic burden before formal diagnosis.
United States Economic Data
The provided context does not contain specific information about the direct healthcare costs, indirect costs, or total economic burden associated with Multiple System Atrophy treatment in the United States according to recent PubMed-published estimates.
Study Design Parameters
Study Design Parameters and Endpoints in Multiple System Atrophy Trials
Trial Characteristics
A systematic review identified 60 clinical trials including 1375 MSA patients. Most studies were small and single-centered, with 51% being single-arm studies and only 28% having a parallel design. Only 13.3% of trials were conducted in a multicenter setting, though three multicenter studies accounted for nearly half (49.3%) of all included patients. Most were early-phase clinical trials that were short in duration and frequently underpowered.
Methodological Issues
The quality of MSA trials has been problematic. Primary outcomes were unclear in 60% of trials, and only 16.7% clearly described the randomization process. Blinding procedures were at high risk of bias in most studies. The dropout/withdrawal rate was high at 23.4%. Inadequate reporting was common for randomization processes, sequence generation, allocation concealment, blinding, and sample size calculations.
Patient Populations
Patient populations varied across studies. One notable study included 105 carefully phenotyped individuals with MSA. Another examined 28 euthyroid patients with probable MSA, divided into MSA-cerebellar type (MSA-C) and MSA-parkinsonian type (MSA-P).
Diagnostic Approaches
Diagnoses were typically based on clinical presentation, with precision-medicine tools such as genetic and molecular testing rarely included. Some studies utilized imaging biomarkers like the midbrain to pons ratio and the Magnetic Resonance Parkinsonism Index.
Example of Trial Design
One detailed trial investigated autologous mesenchymal stem cells (MSC) in patients with MSA-C. This study: - Used change in total UMSARS scores from baseline throughout a 360-day follow-up period as the primary endpoint - Included secondary endpoints measuring changes in UMSARS part II scores, cerebral glucose metabolism, gray matter density, and cognitive performance - Had inclusion criteria requiring probable MSA-C diagnosis and baseline UMSARS scores of 30-50 - Randomized thirty-three patients to receive MSC or placebo - Employed mixed model analysis to evaluate treatment effects over time - Found the MSC group had a smaller increase in UMSARS scores compared to placebo
Current Status and Research Priorities
Despite numerous trials, there is no treatment that cures MSA or slows its progression. The design and quality of reporting is generally unsatisfactory. Experts have identified critical research areas including pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, biomarkers, and trial designs. International collaboration is considered vital for advancing MSA research.