Breakthrough Clinical Results
Praxis Precision Medicines announced positive topline results from the Phase 2 RADIANT study of vormatrigine in patients with focal onset seizures. The study showed a median 56.3% reduction in seizure frequency over eight weeks, with approximately 22% of patients achieving a 100% reduction. A rapid response was observed, with over 54% of patients achieving a 50% reduction in the first week. Vormatrigine was generally well-tolerated. Praxis plans to complete the pivotal POWER1 study in Q4 2025 and initiate POWER2 shortly. The drug is a next-generation sodium channel blocker aiming to be a first-line treatment for focal epilepsy.
Key Highlights
- 56.3% median reduction in seizure frequency over 8 weeks
- Approximately 22% of patients achieved 100% seizure reduction
- Rapid response: >54% achieved 50% reduction in the first week
- Vormatrigine was generally well-tolerated
Incidence and Prevalence
Global Estimates of Focal Onset Seizures
Focal epilepsies account for approximately 60% of all epilepsies, making them the most common type of epilepsy in adults. This statistic is supported by findings from a 2018 study on whole exome sequencing in routine clinical care.
In terms of global burden, epilepsy affects over 70 million people worldwide according to a 2019 publication. While specific global prevalence rates for focal epilepsy were not provided, several regional studies offer insights into its distribution.
A 2017 study conducted in Tanzania and Zambia found that of 43 patients with epilepsy, 28 had focal or multifocal epilepsy (65%), and 15 (35%) had generalized epilepsy, suggesting a higher prevalence of focal epilepsy in these African regions.
The epidemiology of temporal lobe epilepsy (TLE), the most common type of partial epilepsy, remains somewhat unclear because its diagnosis requires advanced neuroimaging, positive EEG, and appropriate clinical semiology. Current knowledge on TLE epidemiology is primarily derived from tertiary referral centers and inferred from population-based epilepsy studies. Recent recognition of incidentally detected mesial temporal sclerosis in otherwise healthy individuals and benign temporal epilepsy suggests that the true epidemiology of TLE is underestimated.
In a study of children and adolescents in central Oklahoma, the prevalence rate of epilepsy was 4.71 per 1,000, with the highest prevalence in children aged 1-4 years. Males had a slightly higher prevalence rate than females (M:F = 1.1), with the male/female ratio varying by age. The group aged less than 1 year had the highest ratio (M:F = 1.5). Males had higher rates of simple partial epilepsy (M:F = 1.8) and infantile spasms (M:F = 1.5).
This study also revealed that the most common types of epilepsy were tonic, clonic, and tonic-clonic (1.14 per 1,000), complex partial (0.39 per 1,000), and partial seizures secondarily generalized (0.33 per 1,000).
Racial differences in epilepsy prevalence have been observed, with higher prevalence in blacks than in whites, primarily in generalized epilepsies (B:W = 1.8). A study of patients with epilepsy of unknown etiology and an affected first-degree relative found that generalized epilepsy was more common among Caucasian/white subjects (56.8%) than among those with African ancestry (43.1%). Conversely, non-acquired focal epilepsy (NAFE) was more prevalent among subjects of African ancestry (41.5%) compared to Caucasian/white subjects (33.0%).
The incidence of epilepsy has a bimodal distribution with the highest risk in infants and older age groups, though specific incidence rates for focal epilepsy were not provided.
Recent genetic studies have included large sample sizes, with a 2024 study analyzing ULK3 and epilepsy using genome-wide association study data with a sample size of 39,348 for focal epilepsy, indicating significant research interest in this area.
Key Unmet Needs and Target Populations for Focal Onset Seizures
Treatment-Resistant Populations
Approximately one third of patients with epilepsy suffer with medication-refractory epilepsy, and there is a persistent underuse of epilepsy surgery for these patients. Despite available treatments, seizure freedom is achieved in only 60% to 70% of all patients, leaving a significant population with uncontrolled seizures.
Adult patients with drug-resistant focal epilepsy are being prioritized for brivaracetam as add-on therapy, with studies showing these patients are more likely to experience a 50% or greater reduction in seizure frequency compared to placebo.
Surgical Candidates and Barriers
Half of patients potentially eligible for resective surgery decline the operation or further video-EEG monitoring (VEM) procedures. Patients most frequently decline surgery due to general fear of brain surgery (59%) and currently lower seizure frequency (22%). Less epilepsy-related fear is an independent predictor of patients declining surgical treatment.
Alternative Interventions for Non-Surgical Candidates
Neuromodulation treatments including deep brain stimulation (DBS) expand the surgical options and provide alternatives for patients who are not candidates for resective surgery. DBS of the bilateral anterior nucleus of the thalamus is an FDA-approved, safe, and efficacious treatment option for patients with refractory focal epilepsy.
Patients with drug-resistant focal epilepsy are being considered for responsive neurostimulation therapy, with research focusing on identifying biomarkers (particularly functional brain connectivity) to predict clinical response.
Specific Underserved Populations
Asian patients: Eslicarbazepine acetate (ESL) has shown efficacy as adjunctive therapy in adult Asian patients with refractory focal seizures.
Chinese patients: Lacosamide (LCM) efficacy, safety, and tolerability data are still lacking in Chinese epilepsy patients, particularly for pediatric populations and patients with renal or hepatic impairment.
Children: Focal epilepsy disrupts functional connectivity in children both locally and globally, but the wide variety of study methodologies limits clinical application of the results.
Emerging Treatment Approaches
Cenobamate (CNB) is a new anti-seizure medication recently approved for the add-on treatment of focal onset seizures in adult patients, which could pave the way for treatment of refractory or drug-resistant epilepsies.
Therapeutic drug monitoring (TDM) offers a significant opportunity for better management of epileptic patients, especially those undergoing combined therapy.
Patients with highly refractory, highly active epilepsy are being considered for empiric, palliative immunotherapy, with 29% demonstrating a sustained treatment response.
Quality of Life Concerns
Impairment in consciousness during and after seizures remains a debilitating symptom with unclear mechanisms. Identifying cortical physiological changes associated with impaired arousal and responsiveness may help guide future therapies to restore ictal and postictal consciousness.
Driving restrictions represent a significant clinical challenge, with patients experiencing first seizure while driving (FSWD) having higher seizure recurrence rates than those with first seizure at other times.
A total of 25% to 50% of patients also experience neurologic, psychiatric, cognitive, or medical disorders, which must be considered when selecting anti-seizure drugs.
Drug used in other indications
Vormatrigine Clinical Trials Beyond Focal Onset Seizures
I need to inform you that based on the provided context, there is insufficient information to determine what other indications Vormatrigine is being trialled for beyond focal onset seizures, or what intervention models are being used in these trials.
The context does not contain specific details about: - Additional indications for Vormatrigine clinical trials - Intervention protocols for any Vormatrigine trials - Dosing regimens being tested - Study designs for Vormatrigine research - Clinical trial data for non-epileptic indications
Without this information in the provided context, I cannot provide the requested 500-word response about Vormatrigine's additional indications and intervention models.
For accurate information about Vormatrigine clinical trials, I would recommend consulting: - Clinical trial registries such as ClinicalTrials.gov - Medical literature databases like PubMed - Pharmaceutical company publications regarding Vormatrigine - Regulatory authority documents from FDA or EMA