Breakthrough Clinical Results
Cassava Sciences announced positive preclinical results for simufilam in a mouse model of tuberous sclerosis complex (TSC)-related epilepsy. The study, conducted in collaboration with the TSC Alliance, showed simufilam attenuated seizure activity in a dose-dependent manner. These findings are consistent with previous research and support simufilam's potential as a first-in-class treatment. Cassava plans to initiate a Phase 2 proof-of-concept clinical trial in the first half of 2026.
Key Highlights
- Positive preclinical results for simufilam in a TSC-related epilepsy mouse model.
- Simufilam demonstrated a dose-dependent reduction in seizure activity.
- Findings consistent with previous research in a different mouse model.
- Phase 2 proof-of-concept clinical trial planned for H1 2026.
Incidence and Prevalence
Global Estimates of Epilepsy Incidence and Prevalence
Epilepsy represents one of the major brain disorders worldwide, affecting nearly 70 million people globally. The prevalence of epilepsy generally centers around 1% of the global population, though there are wide prevalence differences among various populations across different regions.
Regional Variations
The majority of people with epilepsy live in developing countries, where epilepsy remains a major public health problem. Significant variations exist across sub-Saharan Africa, Latin America, and Asia. Notably, prevalence is lower in Southeast Asia than in sub-Saharan Africa and Latin America.
In West Uganda, a study found a crude prevalence rate of 1.3% (age-standardized rate of 1.1%), with clustering in different villages ranging from 0.2% to 3.4%. The age-specific prevalence was highest between 10 and 19 years, with a rate of 3.6% for the study area as a whole, and up to 10.0% in villages of high epilepsy prevalence.
Recent data from southern Han Chinese (2015) found the one-year prevalence of active epilepsy was 2.8‰, and the five-year prevalence was 3.7‰, with prevalence significantly higher in rural areas than in urban areas.
In the United States (2010-2013), 1.7% of adults aged ≥18 years (4.0 million) had epilepsy, with 1.0% having active epilepsy and 0.7% having inactive epilepsy. The prevalence was significantly higher for non-Hispanic whites (1.9%) and non-Hispanic blacks (1.8%) compared with Hispanics (1.0%).
A study in Philadelphia (2009) found Hispanics had the highest epilepsy risk overall, followed by African Americans, and then Caucasians.
In British Columbia, 5.5 per 1000 children were classified as having epilepsy, with higher prevalence among those with low socioeconomic status.
Developing vs. Developed Countries
The incidence of epilepsy in developing countries appears to be greater than in the industrialized world. The treatment gap (difference between people with active epilepsy and those appropriately treated) varies from 10% in developed countries to 75% in low-income countries.
In Taiwan, epilepsy was diagnosed in 0.8 deaths/100,000 population (1996). Japan reported only 0.17% of the total population with epilepsy (2008), less than one-third of Western countries' rates. In India, epilepsy prevalence in the pediatric age group is 3.13 to 3.73 per 1000.
Contributing Factors
These prevalence differences may be related to the distribution of risk factors such as infectious diseases with neurologic sequel, head injuries, or genetic factors. Stigmatization of people with epilepsy could lead to underestimating the prevalence, even in well-conducted studies.
Refractory epilepsies (resistant to medication) occur in approximately one-third of recently diagnosed patients. In southern Han Chinese populations, the most common causes were cerebrovascular disease (32.3%) and traumatic brain injury (29.0%), with a large treatment gap of 93.4%.
Standardizing the process of epidemiologic monitoring of epilepsy is crucial to improve reliability in data comparison across regions and populations.
Economic Burden
Economic Burden of Treating Epilepsy in USA and Europe
The economic consequences of epilepsy-related morbidity and mortality are substantial worldwide. According to a 2021 study, the cumulative value of lost economic welfare (VLW) related to epilepsy was estimated at $647.37 billion (2016 US dollars, purchasing power parity). These economic welfare losses were equivalent to a mean of 1.45% (±1.00%) of gross domestic product globally. Notably, the value of economic losses attributable to cases requiring neurosurgical consultation was $258.95 billion and for neurosurgical intervention was $155.37 billion.
In the United States, limited specific cost information is available in recent studies. The mean prevalence of epilepsy is estimated at 0.68% in the US. Interestingly, studies have shown statistically higher overall healthcare costs during periods of generic antiepileptic drug (AED) use compared to branded AEDs in both the USA and Canada. This finding was observed in both stable and unstable epilepsy patients, with more pronounced cost increases in patients receiving multiple generic versions. Contrary to expectations, brand-to-generic substitutions of AEDs do not necessarily reduce overall healthcare costs and may even increase them.
In Europe, several country-specific studies provide detailed economic burden estimates:
In the United Kingdom, the total annual cost of established epilepsy was estimated at 1930 million pounds (US$2895 million), with over 69% due to indirect costs (unemployment and excess mortality). The cost per patient with active epilepsy was approximately 4167 pounds (US$6251), while inactive epilepsy cost about 1630 pounds (US$2445) per patient annually. UK studies also evaluated specific treatments: chronic topiramate treatment costs £21,353 per QALY gained, with sensitivity analyses suggesting a range from £19,915 to £24,518 per QALY.
In Denmark, a 2011 study found direct net annual health care and indirect costs were €14,575 for patients compared to €1,163 for controls, resulting in an excess cost of €13,412. Danish patients with epilepsy also received an annual mean excess social transfer income of €4,194.
A Greek study from 2019 evaluated lacosamide treatment, finding it was associated with higher costs (€1,064) and an additional 0.119 QALYs compared with zonisamide, resulting in an incremental cost-effectiveness ratio of €8,938 per QALY gained.
A 2002 study across 14 epilepsy centers found that total annual costs varied significantly across patient groups: 3945 Euro (surgical candidates), 2198 Euro (drug-resistant), 1626 Euro (non-drug-resistant), 1002 Euro (newly diagnosed), 558 Euro (occasional seizures), and 412 Euro (seizure remission).
Across all countries, direct costs peak in the first year after diagnosis and then vary according to the severity of the disease, the response to treatment, and the presence of comorbidity. The main items of expenditure are consistently hospital stay (including day-hospital), followed by drug treatment and outpatient visits. While many countries cover costs through national health systems, out-of-pocket costs may represent a significant fraction of overall expenses, especially in countries with suboptimal public healthcare management.
Simufilam Clinical Trials Beyond Epilepsy
Based on the available information, there is insufficient data to provide a comprehensive answer about other indications for which Simufilam is being trialed beyond epilepsy, or about the intervention models used in these trials.
Simufilam (PTI-125) is an investigational drug that has been primarily studied for Alzheimer's disease. The query suggests it is also being investigated for epilepsy, but specific details about additional indications, intervention protocols, dosage regimens, or administration schedules are not available in the provided context.
Without access to complete clinical trial information, it's not possible to outline:
- Other medical conditions being targeted
- Intervention models used in various trials
- Dosing protocols for different indications
- Primary and secondary outcome measures for non-Alzheimer's trials
- Patient populations being studied
- Trial phases for different indications
For accurate and current information about Simufilam clinical trials across various indications, consulting official clinical trial registries such as ClinicalTrials.gov or reaching out directly to the drug developer, Cassava Sciences, would be recommended.