Precision Medicine Breakthrough in Treatment-Resistant Depression

In a significant advancement for the treatment of treatment-resistant depression (TRD), Denovo Biopharma LLC has reported successful results from its late-stage global clinical trial known as ENLIGHTEN. The study focused on the drug DB104, also named liafensine, which is a novel triple reuptake inhibitor that targets the transporters for serotonin, norepinephrine, and dopamine. This breakthrough is particularly notable as it utilizes a genetic biomarker, DGM4, identified through Denovo’s proprietary big data platform, the Denovo Genomic Marker (DGM™).

The ENLIGHTEN trial was meticulously designed as a randomized, double-blind, and placebo-controlled study, enrolling 197 participants diagnosed with TRD. The trial’s primary goal was to evaluate the efficacy and safety of liafensine in patients who tested positive for the DGM4 biomarker. The results were impressive; patients treated with liafensine showed substantial improvements over the course of six weeks compared to those on placebo. Notably, liafensine outperformed placebo by a significant margin in the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure for assessing depressive symptoms.

Furthermore, the drug met all secondary endpoints, with improvements in the Clinical Global Impressions Scale–Severity (CGI–S) and the Sheehan Disability Scale (SDS), indicating a roughly 36% enhancement over placebo. The Clinical Global Impressions Scale-Improvement (CGI–I) also favored liafensine, reflecting a 0.6-point advantage over placebo. The drug was well-tolerated and maintained an excellent safety record, aligning with the outcomes of previous trials involving over 2,200 subjects.

Matthew Spear, Denovo’s Chief Medical and Development Officer, expressed his enthusiasm for the results, highlighting the drug’s potential to improve depression symptoms by more than 40%, a significant advancement over existing treatments. Wen Luo, Denovo’s CEO and Chief Scientific Officer, emphasized the trial’s success as a milestone for the company, showcasing their innovative biomarker strategy to revitalize late-stage drug development.

Denovo Biopharma is a clinical-stage biopharmaceutical company renowned for its innovative biomarker-driven approach to clinical trials. With a pipeline of eight late-stage drugs, Denovo is dedicated to addressing significant unmet medical needs, particularly in oncology and CNS diseases, with a focus on first-in-class drugs.

The successful ENLIGHTEN trial not only signals a new chapter in the development of TRD treatments but also underscores the potential of precision medicine to transform the approach to CNS disease management. With the next steps involving the search for a global partner to accelerate liafensine's market development, the future holds promise for millions of TRD patients worldwide.