Liafensine significantly improves treatment-resistant depression in phase 2b trial

Key takeaways:

• Liafensine successfully met all of the phase 2b study endpoints.
• This is the first time a genetic biomarker has been used to enrich responders in this patient population.

Liafensine met all safety and efficacy endpoints and demonstrated significant improvements over placebo as a treatment for treatment-resistant depression in the phase 2b ENLIGHTEN trial, according to a manufacturer-issued press release.

Liafensine (DB104, Denovo Biopharma) is a first-in-class triple reuptake inhibitor that targets serotonin, norepinephrine and dopamine transporters. Based on research from the Denovo Genomic Marker biomarker platform, researchers hypothesized that a novel genetic biomarker, termed DGM4, would predict liafensine’s efficacy.

Researchers enrolled 197 patients with treatment-resistant depression in the DGM4-biomarker guided, randomized, double-blind, placebo-controlled global trial. Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score served as the study’s primary endpoint.

Over the 6-week treatment period, the change in MADRS score from baseline for liafensine demonstrated a significant 4.4-point improvement compared with placebo (P = .0056).

The secondary trial endpoints were also met, according to the release. Researchers reported that changes from baseline in both Clinical Global Impressions Scale Severity and Sheehan Disability Scale for liafensine revealed an approximate 36% improvement over placebo.

Further, liafensine showed a 2.3-point improvement in the Clinical Global Impressions Scale, representing a 0.6-point improvement over placebo (P = .0026).

Additionally, liafensine was well-tolerated and demonstrated an excellent safety profile, according to the release.

“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 the 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.”