Bright Minds Biosciences has initiated the BREAKTHROUGH trial, a Phase 2 study designed to assess the safety and efficacy of BMB-101 in adult patients with classic absence epilepsy and developmental epileptic encephalopathy (DEE). This trial marks a significant step forward in addressing drug-resistant epilepsies, where current treatments often fall short.
BREAKTHROUGH Trial Design
The BREAKTHROUGH trial is structured as a basket clinical trial, incorporating a 4-week baseline period, an 8-to-12-week treatment period, and a 4-week follow-up phase for safety monitoring. The study aims to enroll 20 adults, aged 18-65 years, diagnosed with absence epilepsy or a DEE, including rare epilepsy disorders like Jeavons Syndrome. Following the follow-up period, eligible patients can continue receiving BMB-101 in a 12-month open-label extension.
BMB-101: A Novel 5-HT2C Receptor Agonist
BMB-101 is a novel scaffold 5-HT2C Gq-protein biased agonist. Preclinical studies have indicated its efficacy in animal models of Dravet syndrome and various generalized seizures. A prior Phase 1 study, conducted in Australia, evaluated the safety, tolerability, pharmacokinetic (PK) profile, and food effect of BMB-101 in healthy volunteers using single-ascending dose (SAD) and multiple-ascending dose (MAD) designs.
In the Phase 1 trial, both SAD and MAD portions included four cohorts (six drug and two placebo). The SAD phase reached a top dose of 180 mg/70 kg, approaching preclinical exposure limits, and was well-tolerated with a predictable PK profile. Oral paresthesias were the most common adverse event, attributed to the liquid formulation. The MAD phase involved twice-daily dosing for seven days, reaching a top dose of 150 mg/70 kg twice daily, and demonstrated noticeable effects on target biomarkers, including prolactin release and quantitative EEG.
Clinical Significance and Future Implications
Ian McDonald, CEO of Bright Minds Biosciences, stated, "We are excited to advance BMB-101 into this next phase of clinical development as we continue to build on the promising safety and pharmacodynamic data from our Phase 1 trial. With its unique pharmacological profile, we believe BMB-101 has the potential to be a best-in-class 5-HT2C agonist...BMB-101 offers a differentiated treatment option for patients with refractory epilepsy, where current therapies often fall short, and could provide a new standard of care for a much wider population of epilepsy sufferers."
Food effect analysis in 12 participants showed that BMB-101 had a relatively small food effect, suggesting it can be administered without fasting. This flexibility could improve patient compliance and convenience. The ongoing Phase 2 BREAKTHROUGH trial will further elucidate the potential of BMB-101 in addressing the unmet needs of patients with drug-resistant epilepsies.
