Evenamide Shows Benefit as Add-On Therapy for Treatment-Resistant Schizophrenia
Key Clinical Summary
- Evenamide add-on therapy improved outcomes in patients with treatment-resistant schizophrenia or inadequate antipsychotic response, according to post-hoc analysis findings.
- More than half of long-term treated patients no longer met baseline treatment-resistant severity criteria after 1 year.
- Improvements extended beyond symptoms, with gains in social functioning and life engagement across studies.
According to recent post-hoc analyses published in Therapeutic Advances in Psychopharmacology, evenamide, a glutamate modulator, may provide clinically meaningful treatment benefits when added to first- or second-generation antipsychotics in patients with treatment-resistant schizophrenia (TRS).
Study Findings
The researchers analyzed data from 2 phase II/III studies evaluating add-on evenamide therapy in patients with treatment-resistant schizophrenia or inadequate response to antipsychotic treatment. Study 014/015 was a year-long, open-label trial in TRS patients, while Study 008A was a randomized, double-blind, placebo-controlled trial in patients not adequately benefiting from second-generation antipsychotics.
In their analysis of Study 014/15, the investigators found that 55% of patients with TRS who received a year of adjunctive evenamide no longer satisfied baseline TRS severity criteria. Approximately one-fourth of patients also achieved remission, according to predefined literature criteria.
Using a mixed model repeated measures (MMRM) linear regression model for the analysis of Study 008A, which assessed treatment response based on the number of previously failed antipsychotic attempts, the researchers reported a statistically significant drug-placebo difference in patients with a single failed attempt (-4.9, p = 0.0122) and in those with 2 or more failed attempts (-2.36, p = 0.0311) of antipsychotic treatment.
Add-on treatment with evenamide was also associated with improvement in life engagement and social functioning, measured by subdomains of the Positive and Negative Syndrome Scale (PANSS) across both studies. In Study 014/015, PANSS score improvement was progressive over time.
Clinical Implications
For patients who experience persistent symptoms or functional impairment despite treatment with first- or second-generation antipsychotics, the findings from these post-hoc analyses highlight the potential value of targeting glutamatergic dysfunction, rather than dopamine pathways alone.
The observed improvements in social functioning and life engagement are also particularly relevant for clinicians, as these domains are closely linked to quality of life and long-term outcomes in schizophrenia. While the analyses were post-hoc and include open-label data, the consistency of findings across different study designs supports further investigation of evenamide as an adjunctive treatment strategy.
Expert Commentary
“Evenamide, by modulating glutamate in the hippocampus (site of dysfunction), has the potential to treat the symptoms of schizophrenia more broadly, addressing also those poorly managed by the currently available antipsychotics,” wrote Ravi Anand, MD, Chief Medical Officer, Newron Pharmaceuticals, and study coauthors.
The researchers noted that a phase III program including 2 randomized, double-blind, placebo-controlled trials has been initiated to further assess the efficacy and safety of evenamide in TRS patients.
