Breakthrough Clinical Results
Clene, Inc. announced a positive Type C meeting with the FDA regarding its statistical analysis plan for CNM-Au8 in ALS patients. The FDA provided constructive feedback on the proposed analysis of neurofilament light (NfL) biomarker data from an NIH-sponsored Expanded Access Program. Two additional FDA meetings are scheduled for Q3 2025 to discuss ALS survival data and the Phase 2 MS program results. Clene plans to submit a New Drug Application (NDA) for ALS under the accelerated approval pathway in Q4 2025.
Key Highlights
- Positive FDA feedback on CNM-Au8 statistical analysis plan for ALS.
- Two additional FDA meetings scheduled for Q3 2025 to discuss ALS survival data and MS program.
- NDA submission for ALS under accelerated approval pathway planned for Q4 2025.
- CNM-Au8 shows promise in treating both ALS and MS.
Incidence and Prevalence
Global ALS Incidence and Prevalence Estimates
Incidence Rates by Region
The annual incidence rate of ALS varies significantly across different regions and populations worldwide:
- In Japan, a nationwide survey conducted in 2013 found an annual incidence rate of 2.2 per 100,000 people (95% CI 2.1-2.3)
- When adjusted for age and sex using the 2000 U.S. standard population, Japan's incidence rate was 2.3 per 100,000 people (95% CI 2.2-2.4)
- Cuba reported an adjusted death rate from ALS for the population older than 15 years of 0.83 per 100,000
- Brazil showed adjusted mortality rates of 0.61 to 0.89 per 100,000 person-years over 20 years, and 1.77 to 2.3 per 100,000 person-years over 45 years
- In London, the adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3), while in those of European ancestry it was 1.97 per 100,000 person-years (95% CI 1.55-2.48)
- A notable cluster was observed in Middleborough, Massachusetts, with an ALS incidence of 2.51 deaths per 100,000 person-years compared to the statewide rate of 1.26 per 100,000 person-years (1969-1985)
Prevalence Data
- In Japan, the annual crude prevalence rate was reported as 9.9 per 100,000 people (95% CI 9.7-10.1)
Ethnic and Demographic Variations
Significant ethnic variations in ALS incidence have been documented:
- The incidence of ALS in Japanese populations was reported to be much lower than in Caucasian populations of Europe and North America
- Brazil showed a predominance of ALS in Caucasians compared to the general population with an odds ratio of 2.92 (95% CI 2.78-3.07)
- The odds ratio for ALS in blacks was 0.04 (95% CI: 0.03-0.04), in mestizos was 0.05 (0.04-0.07), and in Indians was 0.02 (0.01-0.04)
- In Cuba, the adjusted mortality rate per 100,000 was lower in the mixed population (0.55; CI 0.4-0.72) than in whites (0.93; CI 0.83-1.03) and blacks (0.87; CI 0.62-1.17)
- The overall mortality rate from ALS in Cuba is similar to that described in Hispanic populations in the United States and is lower than in Northern European populations
Age and Gender Patterns
ALS shows consistent patterns regarding age and gender:
- In Japan, the age group with the highest prevalence and incidence was 70-79 years, with a male-female ratio of approximately 1.5
- Brazil reported an average age of ALS patients of 62.7 ± 13.2 years, with a predominance of males (1.3:1)
- In Cuba, the mean age at death was 63.7 years with a slight male predominance (1.1:1)
Genetic Factors
- Approximately 10% of ALS cases have a family history
- Pathogenic variants in the SOD1 gene are the second most frequent causative factor of genetics-based ALS worldwide, after C9ORF72 hexanucleotide repeat expansion
- Research has identified clinically significant pathogenetic variants in 14.43% of ALS cases
Economic Burden
Economic Burden of Treating Amyotrophic Lateral Sclerosis (ALS) in the USA and Europe
Economic Burden in Europe
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that imposes a great burden on patients, families, and society across Europe. The economic impact varies significantly between countries:
- In Denmark, data from the Danish National Patient Registry (1998-2009) showed an annual mean excess health-related cost of €18,918 per ALS patient.
- Germany reported substantially higher total annual costs per patient at €83,060.
- A Spanish study from 2004 calculated a mean annual cost per patient of €36,194, with major cost categories including informal care, early retirement, medications, and orthopaedic devices.
- A systematic review found that most studies reported total costs per patient ranging from €9,741 to €114,605.
- At the national level, the total costs for ALS varied between €149 million and €1,329 million according to the systematic review.
The health-related quality of life for ALS patients in Europe is severely impacted, with the Spanish study reporting a mean EQ-5D index score of 0.18 and mean EQ-5D VAS score of 29.
When comparing different motor neuron diseases in Germany, ALS had cost-utilities estimated at €138,960/QALY, which was lower than SMA (€525,033/QALY) but higher than HSP (€49,573/QALY).
Economic Burden in the USA
In the United States, the economic burden increases significantly as the disease progresses:
- Annualized costs for people living with ALS (plwALS) were $31,411 in early-stage, $51,481 in middle-stage, and $121,903 in late-stage disease.
- The higher costs in later stages were primarily driven by increased frequency and cost per hospital admission.
- The national economic burden of ALS in the US was estimated at US$ 279-472 million (standardized to 2015 US$).
- The annual total cost per patient in the US was estimated at US$ 69,475 (standardized to 2015 US$), which was higher than in other countries.
Healthcare Resource Utilization
Healthcare resource utilization (HCRU) increases with disease progression in the US:
- Late-stage ALS patients had more hospital admissions (0.74 vs 0.15 in early stage)
- More outpatient visits (48.54 vs 26.81)
- More emergency department visits (1.03 vs 0.46)
- More prescriptions (12.72 vs 9.23) over 12 months
A prospective study of 18 US ALS centers found the mean salary/benefit cost per patient per clinic was $507 (range $258-$806 across centers), and the mean total salary/benefit cost per clinic day for all providers was $2,964 (range $1,692-$5,236).
Common Factors Across Regions
Several factors consistently drive costs in both Europe and the USA:
- Studies confirmed a rise in costs with disease progression, peaking close to the death of a patient.
- The main cost drivers were informal care (across all motor neuron diseases) and disease-modifying treatments.
- The main predictors of high cost of illness were disease progression and loss of individual autonomy.
- ALS patients had significantly higher rates of health-related contact and medication use and higher socioeconomic costs.
- Patients with ALS had very low employment rates, while those in employment had a lower income level than control subjects.
Researchers note that further research is needed to establish a cost-effective health policy in consideration of disease severities.
HTA Approvals
Drug Approvals for ALS by UK, France, and Germany in the Last Three Years
I cannot provide specific information about drug approvals for Amyotrophic Lateral Sclerosis (ALS) by the Health Technology Assessment (HTA) agencies of the UK, France, and Germany over the last three years, as this information is not present in the provided context.
The context provided does not contain any relevant information about: - ALS drug approvals - HTA decisions in the UK, France, or Germany - Any specific medications for ALS - Recent regulatory decisions regarding ALS treatments
Without this specific information in the context, I cannot accurately address which drugs, if any, have been approved for ALS by these agencies in the specified timeframe.