Breakthrough Clinical Results
Prilenia Therapeutics and Ferrer announced the presentation of their planned pivotal Phase 3 study of pridopidine in Amyotrophic Lateral Sclerosis (ALS) at the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) 2025 Annual Meeting. The study aims to confirm encouraging Phase 2 data regarding global function, speech, respiratory function, and survival. Enrollment is expected to begin in early 2026, focusing on participants with early and rapidly progressive ALS. The study will assess the efficacy and safety of pridopidine, with endpoints including changes in ALSFRS-R scores, survival, and measures of speech and respiratory function.
Key Highlights
- Prilenia and Ferrer to present Phase 3 study design for pridopidine in ALS at NEALS 2025.
- Phase 3 study aims to confirm Phase 2 data showing improvements in global function, speech, respiratory function, and survival.
- Enrollment for the Phase 3 study is expected to begin in early 2026, focusing on early and rapidly progressive ALS patients.
- Pridopidine's potential to enhance neuronal survival by mitigating ER stress will also be presented.
Incidence and Prevalence
Global Estimates of ALS Incidence and Prevalence
Global Overview
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of bulbar and limb function, with patients typically dying from respiratory failure within 3 years of symptom onset. The global annual prevalence of ALS is estimated at 4.5 per 100,000 population.
Regional Incidence Rates
United States
In the United States, a 2021 study analyzing administrative claims data from over 100 million patients found average annual incidence estimates of 1.48 and 1.37 per 100,000 population. Predictive modeling indicates an increasing trend in both incident and prevalent cases through 2060.
Europe
In Europe, the incidence of ALS is 2-3 cases per 100,000 individuals, with an overall lifetime risk of developing the disease at 1:400.
Latin America
A systematic review of Latin American studies found standardized incidence ranging from 0.3 per 100,000 person-years in Ecuador to 3.6 per 100,000 person-years in Uruguay. In Brazil, a 2017 study found the adjusted mortality rate for ALS was 0.61 to 0.89/100,000 person-years over 20 years, and 1.77 to 2.3/100,000 person-years over 45 years.
Africa
In South Africa's Western Cape Province (2014-2018), the crude incidence rate was 1.09 per 100,000 person-years, with substantial differences between population groups: highest in those of European ancestry (2.62), lowest in those of African ancestry (0.56), and intermediate in those of mixed ancestry (1.09).
Regional Prevalence Rates
United States
The National ALS Registry reported U.S. prevalence rates of 4.3 per 100,000 during 2010-2011, increasing to 4.7 per 100,000 in 2012 and 5.0 per 100,000 in 2013. A 2021 study found point prevalence estimates of 6.85 and 5.16 per 100,000 population.
Europe
In Germany, a 2018 study projected that ALS prevalence will rise to about 9.2-9.8/100,000 person-years by 2050.
Middle East
A 2017 study in Israel found a relatively high prevalence of ALS at 8.1 per 100,000 population in 2013.
Demographic and Genetic Factors
Epidemiological studies show variation in incidence, mortality and prevalence between geographical areas and populations, suggesting that genetic factors linked to populations' ancestries, along with environmental and lifestyle factors, play significant roles.
There is a predominance of ALS in Caucasians compared to other ethnic groups. In Brazil, Caucasians showed an odds ratio (OR) of 2.92 compared to the general population. The C9orf72 repeat expansion occurs in 21%-57% of familial ALS and 3%-21% of sporadic ALS among Caucasians, compared to only 2.8% in familial ALS and 0.4% in sporadic ALS in Japanese populations.
The burden of motor neuron diseases is currently more relevant in high-income countries but increasing at the highest rate in low and middle-income countries.
Study Design Parameters
Study Design Parameters and Endpoints in Key ALS Trials
Study Designs
- Cross-sectional imaging studies provide valuable pathological insights into neurodegenerative changes
- Longitudinal studies are crucial for detecting subtle progressive changes over short periods
- Three time-point longitudinal studies explore anatomical patterns of disease spread using MRI metrics
- Multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) analyze white matter structural connectivity
- Single-centre prospective case-control studies assess corneal nerves using in vivo confocal microscopy
Patient Populations
- Studies typically include 15-51 ALS patients compared with matched healthy controls
- Some studies specifically focus on ALS patients with C9orf72 mutations
- According to eligibility criteria, approximately 80% of incident ALS cases are eligible for clinical trials under the Airlie House criteria
- Genetic testing is increasingly important, with guidelines recommending single-step genetic testing for all ALS patients
Assessment Tools
- ALSFRS-R (ALS Functional Rating Scale-Revised) is a primary outcome measure with 99.5% complete data, 0.91 within-subject correlation, and best survival prediction
- Edinburgh Cognitive and Behavioural ALS Screen (ECAS) with alternate versions to avoid practice effects
- MiND-B (Motor Neuron Disease Behavioural Instrument) detects behavioral changes, measuring apathy (75%), disinhibition (66%), and stereotypical behavior (58%)
- Other tools include Montreal Cognitive Assessment (MoCA), Electroencephalogram (EEG), and automated algorithms for corneal parameter evaluation
Endpoints and Biomarkers
- ALSFRS-R is a key endpoint where one-unit change in patient-perceived clinical function parallels a 9-point decrease
- Other outcome measures include forced vital capacity, manual muscle testing, and quality of life assessments
- Structural MRI metrics: cortical thickness, grey matter density, white matter alterations
- T1-relaxation times along the corticospinal tract
- CSF sTREM2 levels as potential disease monitoring markers
- Corneal parameters including nerve fibre density and branch density
- Neuroimaging endpoints face limitations including high costs, limited accessibility, and lack of standardization
Evolution of Trial Designs
- A 2012 systematic review found only one randomized controlled trial meeting inclusion criteria
- Successive failures of clinical trials have underlined the need for new strategies based on innovative tools
- Biomarker data is increasingly used to improve clinical trial designs
- With the advent of disease-modifying treatments, emphasis has shifted to timely diagnosis for more effective clinical management
- Artificial intelligence models show promise with 94.3% sensitivity and 98.9% specificity for ALS detection
Key Findings
- White matter degeneration can be detected early but shows limited progression over time
- Grey matter pathology is relatively limited at baseline but exhibits relentless progression
- Cognitive status overall did not change over a 7-month period despite progression of motor weakness
- Behavioral symptoms may develop over time even when executive function remains stable
Other Drugs with Similar Mechanism of Action as Pridopidine
Insufficient information available. Based on a thorough review of the available data, there is currently no information regarding other drugs being trialed for the same indication using the same mechanism of action (MoA) as pridopidine. Similarly, no details are available about the intervention models used in these trials.
The requested information about pridopidine alternatives, their clinical trials, mechanism of action comparisons, and intervention models cannot be provided at this time due to lack of relevant data.
For a comprehensive understanding of drugs with similar MoA to pridopidine and their trial methodologies, additional research from clinical trial databases, pharmaceutical publications, and medical literature would be necessary.