Filana Therapeutics receives FDA clearance to advance simufilam into a Phase 2a trial for refractory TSC-related epilepsy, with screening expected in Q1 2027.
Written By: Rishabh Sonawane, BPharm
Reviewed By: Pharmacally Editorial Team
Filana Therapeutics has received FDA clearance to resume clinical development of simufilam in tuberous sclerosis complex (TSC)-related epilepsy, with patient screening for a planned Phase 2a proof-of-concept study expected to begin in the first quarter of 2027.
Simufilam was previously developed by Cassava Sciences for Alzheimer’s disease. Following the company’s corporate name change to Filana Therapeutics in 2026, the program is now being advanced in TSC-related epilepsy and other potential filamin A-related indications.
Why FDA Placed the Trial on Clinical Hold
The FDA placed the proposed TSC-related epilepsy study on full clinical hold on December 15, 2025, before patient enrollment began. According to the company’s SEC filing, the agency requested additional information, including additional preclinical data and modifications to the proposed clinical trial protocol, before the study could proceed.
During the hold, Filana worked to address the agency’s requests while completing trial-readiness activities. The FDA subsequently lifted the clinical hold in September 2026, allowing the company to progress toward study initiation and patient enrollment.
Phase 2a Trial to Evaluate Seizure Outcomes
The planned multicenter Phase 2a study will enroll approximately 40 patients aged 12 to 55 years with refractory TSC-related seizures. The 16-week trial will randomize participants to evaluate two doses of simufilam under double-blind conditions.
The study will assess safety, tolerability, and pharmacokinetics, along with seizure-related measures including seizure frequency, seizure intensity and duration, nighttime seizures, and sleep-related outcomes.
Patients who complete the 16-week double-blind treatment period will be eligible to enter a 48-week extension study. The resulting data will help inform the subsequent development path for simufilam, including potential studies in younger patient populations.
Simufilam Targets Filamin A
Simufilam is an oral small molecule intended to modulate the filamin A (FLNA) protein. Its development in TSC-related epilepsy is supported by findings from two preclinical mouse models.
Research conducted in the laboratory of Angélique Bordey, PhD, at Yale School of Medicine found that simufilam reduced seizure frequency in a mouse model of focal-onset seizures associated with TSC-related pathology.
In a separate study conducted through the TSC Alliance Preclinical Consortium using a TSC-knockout mouse model, simufilam attenuated the progression of seizure activity in a dose-dependent manner.
Filana holds an exclusive worldwide license from Yale University covering intellectual property supporting the use of simufilam in TSC-related epilepsy.
TSC-Related Epilepsy Remains a Significant Unmet Need
TSC is a rare genetic disorder caused by mutations in the TSC1 or TSC2 gene. These mutations disrupt the mechanistic target of rapamycin (mTOR) pathway and can lead to tumor formation in multiple organs, along with neurological complications.
Epilepsy affects approximately 80% to 90% of people with TSC, and most patients who develop seizures experience onset within the first year of life. Despite multiple available antiseizure treatments, more than 60% of patients with TSC-related epilepsy remain refractory to therapy.
This persistent treatment resistance highlights the need for additional approaches that target biological pathways associated with TSC-related seizure activity.
Patient Screening Expected in Early 2027
Filana has engaged a clinical research organization, identified clinical trial sites, and begun recruiting potential investigators as it prepares for the study. The company is also working with the TSC Alliance and the broader TSC community to support patient engagement and trial execution.
Patient screening is expected to begin in the first quarter of 2027. The Phase 2a study will provide the first clinical evaluation of simufilam in TSC-related epilepsy and will assess whether findings from preclinical models translate into measurable effects on seizure-related outcomes in patients.
The results will help determine the next stage of clinical development, including the potential expansion of evaluation into younger patients with TSC-related epilepsy.
Reference
Filana Therapeutics Announces FDA Lift of Clinical Hold on Simufilam, Enabling Phase 2a Study in TSC-Related Epilepsy, Filana Therapeutics, 22 September 2026
About the Writer
Rishabha Sonawane, B.Pharm (LinkedIn) is healthcare writer with a strong interest in medical writing, regulatory affairs, clinical research, and AI-driven drug discovery. He has completed specialized training from the NIH and ICMR in clinical pharmacology, clinical research, and scientific writing. Passionate about evidence-based healthcare communication, he focuses on translating complex scientific research into clear, accurate, and engaging medical content.