Newly Initiated Phase 2 BREAKTHROUGH Trial to Test 5-HT2C Receptor Agonist BMB-101 in Drug-Resistant Epilepsies
BMB-101, a 5-HT2C receptor agonist, will be tested in a cohort of 20 adults aged 18 to 65 with absence epilepsy or a developmental encephalopathy for an 8-to-12-week treatment period.
Ian McDonald
According to an announcement from Bright Minds Biosciences, the company has initiated a new phase 2 study, dubbed BREAKTHROUGH, that will assess the safety and efficacy of its investigational agent BMB-101 in adults with classic absence epilepsy and development epileptic encephalopathy (DEE). The therapy, a 5-HT2C receptor agonist, has previously demonstrated efficacy in animal models of Dravet syndrome and numerous models of generalized seizures.1
The study, designed as a basket clinical trial, features a 4-week baseline period, 8-to-12-week treatment period, and a 4-week follow-up phase for additional safety monitoring. BREAKTHROUGH is expected to include 20 adults aged 18-65 years old with absence epilepsy or a DEE. These comprise a range of rare epilepsy disorders, including epilepsy with eyelid myoclonia, also known as Jeavons Syndrome. Following the conclusion of the follow-up period, patients may be eligible to receive BMB-101 in an open-label extension that will last 12 months.
"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,” Ian McDonald, chief executive officer at Bright Mind Biosciences, said in a statement.1 "With its unique pharmacological profile, we believe BMB-101 has the potential to be a best-in-class 5-HT2C agonist. In our Phase 1 study, we demonstrated central target engagement, which, in conjunction with the wealth of 5-HT2C data within refractory epilepsies, gives us great confidence in this study."
BMB-101, a novel scaffold 5-HT2C Gq-protein biased agonist, was previously assessed in a 3-part, phase 1 study. The Australian-based study evaluated the safety, tolerability, pharmacokinetic (PK), and food effect of the agent in a single-ascending dose (SAD) and multiple ascending dose (MAD) fashion in healthy volunteers.
Both the MAD and SAD portions included 4 cohorts (6 drug and 2 placebo). In the SAD phase, a single dose of BMB-101 reached its planned top dose of 180 mg/70 kg, and approached preclinical exposure limits. The therapy was well tolerated, had a predictable PK, with oral paresthesias as the most common adverse event as a result of the liquid formulation. In the MAD, twice a day dosing for 7 days after meals resulted in a top dose of 150 mg/70 kg twice day, with noticeable effects on target biomarkers such as prolactin release and quantitative EEG.2
An analysis on food effect in 12 participants showed that BMB-101 had a relatively small effect, with investigators concluding that the therapy may be administered without the need for fasting. This group of patients crossovered with and without breakfast at a dose of 120 mg/70 kg.
McDonald added, "This compound is not only poised to make a significant impact in both the DEE and Absence Epilepsy communities but also has broad applicability across the 30% of all epilepsy patients who experience drug resistance. 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. We would like to thank the AECTN and the Epilepsy Study Consortium for their contributions to our upcoming study."
