Comprehensive Report on Bavisant (DB12299): An Investigational Histamine H3 Receptor Antagonist

I. Executive Summary

Bavisant (DrugBank ID: DB12299), also known by its research codes JNJ-31001074 and BEN-2001, is an investigational small molecule drug. Its primary mechanism of action is as a potent and selective antagonist or inverse agonist of the histamine H3 (H3R) receptor, a target predominantly expressed in the central nervous system (CNS).[1] By modulating H3R activity, Bavisant was hypothesized to increase the release of several key neurotransmitters, including histamine, acetylcholine, norepinephrine, and dopamine, thereby promoting wakefulness and enhancing cognitive functions.[2]

Initially developed by Johnson & Johnson (Janssen), Bavisant showed promise in preclinical models for disorders related to cognition and wakefulness.[6] This led to a broad clinical development program investigating its utility in Attention Deficit Hyperactivity Disorder (ADHD) in both adult and pediatric populations, narcolepsy, and alcoholism, alongside extensive Phase 1 pharmacokinetic and drug interaction studies.[8] However, a key Phase 2 study (NCT00880217) in adults with ADHD failed to demonstrate significant clinical efficacy compared to placebo, even though active comparators (atomoxetine and OROS methylphenidate) showed clear benefits.[11] This lack of efficacy led to the discontinuation of Bavisant's development for ADHD and subsequently for narcolepsy by Johnson & Johnson.[13]

Following these discontinuations, Bavisant (re-designated BEN-2001) was investigated by BenevolentAI for the treatment of Excessive Daytime Sleepiness (EDS) in patients with Parkinson's Disease (PD).[2] A Phase 2b dose-finding study (CASPAR, NCT03194217) was completed, and while trial registry information indicates "results posted" [15], external research commentary suggests these results were negative.[16]