Denovo Biopharma Receives US FDA Fast Track Designation for Liafensine

Denovo Biopharma Receives US FDA Fast Track Designation for Liafensine

By, Admin 14 October 2024

Denovo Biopharma receives US FDA fast track designation for its liafensine for treating patients with treatment-resistant depression

Overview

Denovo Biopharma LLC, a pioneer in applying precision medicine to development of innovative drugs, announced that the US Food and Drug Administration (FDA) has granted fast track designation for its drug candidate, DB104 (liafensine) being developed for treating patients with treatment-resistant depression (TRD).

About FTA

Fast track designation may potentially expedite the review of a drug that is intended for the treatment of a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need for such a disease or condition.

Statement from the CTO: Denovo

  • This US 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 US FDA has recognized our innovative biomarker approach and will continue to work with the agency to bring this biomarker-based precision medicine to treatment-resistant depression patients.

About Treatment-Resistant Depression

  • Treatment-resistant depression is the most difficult depression to treat and TRD patients have limited treatment options that are often associated with significant treatment-related toxicities. 
  • Furthermore, clinicians have challenges identifying the appropriate therapies that most likely benefit these patients. 
  •  Denovo’s discovery of a novel pharmacogenomic biomarker, DGM4, presents a new era for liafensine, a first-in-class triple reuptake inhibitor. 
  • The positive results from the biomarker-guided phase 2b ENLIGHTEN clinical trial, which met all endpoints including the primary endpoint of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline at 6 weeks vs. control (p=0.0056), represent a major advance in TRD as well as the application of precision medicine to psychiatric diseases. 
  • Liafensine’s safety profile was also favorable, without reports of side effects common for approved TRD drugs, such as dissociation, respiratory depression, movement disorders, and metabolic dysfunction with morbid weight gain.

Epidemiology: Major Depressive Disorder

  • More than 23 million people in the US alone suffer from major depressive disorder (MDD). 
  • Over 30% patients with MDD do not benefit from currently available antidepressants and are diagnosed with treatment-resistant depression (TRD). 
  • TRD remains a major unmet medical need as there are few approved pharmacological agents for TRD and overall outcomes remain poor.

First-In-Class Triple Reuptake Inhibitor: Liafensine

  • Liafensine is a first-in-class triple reuptake inhibitor targeting transporters for serotonin, norepinephrine, and dopamine. 
  • It was licensed from Albany Molecular Research, Inc. (now Curia) and was previously developed by Bristol Myers Squibb (BMS: recently obtained FDA approval for Cobenfy, a first-in-class treatment for schizophrenia), who had conducted two large phase 2b clinical trials in TRD which failed in non-biomarker-selected patient population. 
  • Denovo’s unique artificial intelligence (AI) and whole genome sequencing (WGS)-based Denovo Genomic Marker (DGM) biomarker platform allowed discovery of a novel genetic biomarker, termed DGM4, with strong correlation of DGM4-positive status with liafensine’s efficacy in the BMS studies.