FDA Fast Tracks Biomarker-Guided DB104 for Treatment-Resistant Depression

Denovo Biopharma, a leader in precision medicine and innovative drug development, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for DB104, also known as liafensine. This designation is designed to speed up the review process for drugs that treat serious conditions and meet unmet medical needs, highlighting the urgent need for new treatment options for Treatment-Resistant Depression (TRD).

TRD is the most challenging form of depression to manage, with patients often experiencing limited treatment options and significant side effects from existing therapies. Clinicians face difficulties in identifying effective treatments for TRD patients. Denovo Biopharma has discovered a novel pharmacogenomic biomarker, DGM4™, which marks a new advancement in the treatment landscape for liafensine. Liafensine is the first of its kind as a triple reuptake inhibitor, targeting serotonin, norepinephrine, and dopamine transporters.

The Phase 2b ENLIGHTEN clinical trial for liafensine, guided by the DGM4 biomarker, showed promising results. The trial met all its endpoints, including the primary endpoint of change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline at six weeks compared to the control group (p=0.0056). These results signify a significant breakthrough in TRD treatment and the application of precision medicine in psychiatric disorders. Additionally, liafensine demonstrated a favorable safety profile, with no reports of common side effects associated with approved TRD medications such as dissociation, respiratory depression, movement disorders, and significant weight gain.

Dr. Xiao-Xiong Lu, Chief Technical Officer at Denovo Biopharma, emphasized that the FDA's Fast Track designation would accelerate the development of liafensine. Dr. Lu expressed satisfaction with the FDA's recognition of their innovative biomarker approach and commitment to continue collaborating with the agency to deliver this precision medicine to TRD patients.

In the United States, over 23 million individuals suffer from major depressive disorder (MDD), with more than 30% of these patients not responding to current antidepressant treatments, thereby qualifying as TRD patients. This condition represents a significant unmet medical need, given the limited number of approved pharmacological treatments and generally poor outcomes.

Liafensine, a first-in-class triple reuptake inhibitor, was licensed from Albany Molecular Research, Inc. (now Curia) and previously developed by Bristol-Myers Squibb (BMS). BMS conducted two large Phase 2b clinical trials in TRD, which did not succeed in a non-biomarker-selected patient population. Denovo's advanced artificial intelligence (AI) and whole genome sequencing (WGS)-based Denovo Genomic Marker (DGM™) platform enabled the discovery of the novel genetic biomarker DGM4™, showing a strong correlation between DGM4-positive status and liafensine's efficacy in BMS’s studies. The ENLIGHTEN study results confirmed the use of DGM4 as a predictive biomarker for liafensine’s effectiveness in TRD patients, marking a first in the field of psychiatric genetic biomarkers.

Denovo Biopharma is a clinical-stage biopharmaceutical company that leverages novel biomarker strategies to conduct efficient clinical trials focused on targeted patient subpopulations, thereby increasing the likelihood of success. The company’s pipeline includes seven late-stage drugs addressing major unmet medical needs in central nervous system diseases and oncology, many of which are first-in-class drugs held under global rights.