Fast Track Designation Granted to Liafensine for Treatment-Resistant Depression

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The US Food and Drug Administration (FDA) has granted Fast Track designation to Denovo Biopharma LLC’s DB104 (liafensine) for the treatment of patients with treatment-resistant depression (TRD).¹

"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."

Denovo discovered the novel pharmacogenomic biomarker, DGM4, which researchers hypothesized would predict liafensine’s efficacy.² This presents a new era for the first-in-class triple reuptake inhibitor, liafensine, which targets targeting transporters for serotonin, norepinephrine, and dopamine. This is the first time a genetic biomarker has been used to help those in this patient population. The biomarker-guided phase 2b ENLIGHTEN clinical trial of liafensine 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). Liafensine demonstrated a favorable safety profile, without reports of adverse effects common for currently approved TRD drugs, including dissociation, respiratory depression, movement disorders, and metabolic dysfunction with morbid weight gain.

“I am really excited about these positive results in treatment-resistant depression, which is one of the toughest central nervous system (CNS) diseases to treat. The results are remarkable as we have seen more than 40% improvements in depression symptoms, of greater magnitude than some approved drugs in current use,” Matthew Spear, MD, Denovo’s chief medical officer and chief development officer, said in a press release. “It also represents a breakthrough in using precision medicine for CNS diseases, as it is the first time a genetic biomarker has been used to enrich responders in TRD patients, which is the key to our success.”²

Other potential therapies under investigation for treatment-resistant depression include VLS-01, an oral transmucosal film formulation of DMT; extended-release oral ketamine formulations; and deep brain stimulation.

References

1. FDA grants fast track designation for biomarker-guided DB104 (liafensine) in patients with treatment-resistant depression (TRD). PR Newswire. News release. Accessed October 9, 2024. https://www.prnewswire.com/news-releases/fda-grants-fast-track-designation-for-biomarker-guided-db104-liafensine-in-patients-with-treatment-resistant-depression-trd-302270948.html

2. Liafensine significantly improves treatment-resistant depression in phase 2b trial. Healio. News release. April 15, 2024. Accessed October 9, 2024. https://www.healio.com/news/psychiatry/20240415/liafensine-significantly-improves-treatmentresistant-depression-in-phase-2b-trial