A Biomarker-Guided, Randomized, Placebo-Controlled Efficacy and Safety Study of Liafensine in Patients With TRD

Phase 2 Completed 197 enrolled Denovo Biopharma LLC

RandomizedParallel-groupDouble-blindTreatment

Summary

This study was conducted as a randomized, double-blind, placebo-controlled, multi-center Phase 2b study. Approximately 180 subjects with treatment resistant depression who meet all eligibility criteria will be enrolled. The primary endpoint is to demonstrate liafensine is superior to placebo in DGM4 positive patients with TRD.

Timeline

Start: 2022-06-29
Primary completion: 2024-02-06
Completion: 2024-03-05

Outcome

Met primary endpoint

registry analysis (superiority test); Liafensine 1mg or 2 mg vs Placebo; p = 0.0056; LS Mean Difference -4.4 (95% CI -7.6 to -1.3); MMRM NCT05113771 ↗

paper The mean (SE) MADRS score change in these patients was -15.4 (0.9) for liafensine (including both 1- and 2-mg doses) vs -11.0 (1.3) for placebo PMID 40928787 ↗

release “The primary endpoint was met: the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score” denovobiopharma.com ↗

Publications

Wang G, Aguado M, Spear MA, Alphs L, Chen C, Huang H, Lu XX, Doostzadeh J, Wu S, Wang S, Patel A, Nemeroff CB, Wang Z, Li A, Luo W. ANK3 as a Novel Genetic Biomarker for Liafensine in Treatment-Resistant Depression: The ENLIGHTEN Randomized Clinical Trial. JAMA Psychiatry. 2025 Dec 1;82(12):1186-1194. doi: 10.1001/jamapsychiatry.2025.2416.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Liafensine	Small molecule	1 mg	Oral
Subject	Liafensine	Small molecule	2 mg	Oral

Indications

No indication recorded.