Denovo Biopharma LLC has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its drug candidate DB104 (liafensine) in development for treatment-resistant depression (TRD). The designation aims to accelerate the review process for drugs addressing serious conditions with unmet medical needs.
Liafensine is a first-in-class triple reuptake inhibitor targeting serotonin, norepinephrine, and dopamine transporters. TRD affects over 30% of individuals with major depressive disorder (MDD) in the U.S., representing a significant challenge due to limited treatment options and associated toxicities.
Precision Medicine Approach
Denovo's approach involves a novel pharmacogenomic biomarker, DGM4, identified using artificial intelligence (AI) and whole genome sequencing (WGS). The biomarker is designed to predict liafensine's efficacy, potentially revolutionizing the treatment of psychiatric diseases through precision medicine.
The Phase 2b ENLIGHTEN clinical trial (NCT05113771) evaluated liafensine in 197 TRD patients, including both DGM4-positive and DGM4-negative individuals. The study met its primary endpoint, demonstrating a statistically significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline at 6 weeks in DGM4-positive patients (p=0.0056).
Safety and Efficacy
The ENLIGHTEN trial also highlighted a favorable safety profile for liafensine, with no reports of common side effects associated with existing TRD treatments, such as dissociation, respiratory depression, movement disorders, or metabolic dysfunction with morbid weight gain.
"This FDA Fast Track designation is an accelerator for liafensine's development," said Xiao-Xiong Lu, PhD, Denovo's Chief Technical Officer. "We are pleased that FDA has recognized our innovative biomarker approach and will continue to work with the agency to bring this biomarker-based precision medicine to TRD patients."
Previous Development
Liafensine was previously under development by Bristol Myers Squibb (BMS), who conducted two Phase 2b clinical trials in TRD that failed in non-biomarker-selected patient populations. Denovo's DGM4 biomarker platform allowed for the identification of patients most likely to respond to the drug.
