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T94

LB-102 FOR ACUTE SCHIZOPHRENIA IN ADULTS: RESULTS FROM THE PHASE 2 NOVA1 CLINICAL TRIAL, FOCUSED ON PANSS TOTAL SCORE RESPONDER AND CGI-S REMITTER RATES

Christoph U Correll — Anna Eramo2, Rezi Zawadzki2, George Nomikos2, Leslie Callahan2, Niccolo Bassani3, John Kane4 1The Donald and Barbara Zucker School of Medicine, Northwell, Universitätsmedizin Charité Berlin, German Center for Mental Health (DZPG), 2LB Pharmaceuticals Inc, 3Worldwide Clinical Trials, 4The Donald and Barbara Zucker School of Medicine

2026 ASCP Annual Meeting

Background

LB-102 (N-methylated amisulpride) is a novel benzamide antipsychotic currently under development for the treatment of patients with acute schizophrenia as well as other neuropsychiatric diseases. Primary analysis of the large-scale, phase 2 NOVA1 study in adults with acute schizophrenia (NCT06179108) highlighted that LB-102 had a clinically significant treatment effect on the Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impression of Severity (CGI-S) score after 4 weeks of treatment. This analysis explores response rates to LB-102 on the PANSS total score and CGI-S at the end of Week 4.

Methods

NOVA1 was a randomized, double-blind, placebo-controlled trial in eligible adults (18–55 yr) diagnosed with schizophrenia. Participants were randomized (3:3:3:1) to oral once-daily placebo (PBO), LB-102 50mg, LB-102 75mg, or LB-102 100mg (exploratory). The primary analysis was change from baseline to Week 4 in PANSS total score, with effect sizes and responder/remitter rates calculated based on observed cases. Post hoc analyses were conducted to determine PANSS total score response rates of ≥20%, ≥30%, and ≥40% at Week 4, with PANSS item scores rescaled (0–6; total score range: 0–180) to adjust for the mathematical floor effect. CGI-S remission was defined, a priori, as a participant with a CGIS rating of 3 (mildly ill), 2 (borderline mentally ill), or 1 (normal, not at all ill) at Week 4.

Results

359 participants were randomized (PBO, n=108; 50mg, n=107; 75mg, n=108; 100mg, n=36), with 261 (73%) completing the 6-week trial. LB-102 met the primary endpoint, with mean changes from baseline to Week 4 in PANSS total score being -9.3 (PBO, n=93), -14.3 (50mg, p=0.0009 vs PBO; effect size=0.61, n=91), -14.0 (75mg, p=0.0022; effect size=0.41, n=84), and -16.1 (100mg, nominal p=0.0017; effect size=0.83, n=23). Post hoc (floor-adjusted) analysis of PANSS total scores demonstrated a higher proportion of responders for all LB-102 doses compared to PBO for the ≥20% (50mg, 57.1%, p=0.03; 75mg, 53.6%, p=0.02; 100mg, 78.3%, p=0.001 vs PBO, 38.7%) and ≥30% (50mg, 31.9%, p=0.03; 75mg, 31.0%, p=0.01; 100mg, 39.1%, p=0.02 vs PBO, 16.1%) PANSS total score responders, as well as ≥40% PANSS total score responders for LB-102 50mg (20.9%, p=0.01) and 75mg (16.7%, p=0.02) compared to PBO (6.5%). All LB-102 doses demonstrated significantly greater improvements from baseline to Week 4 in CGI S score compared to PBO (50mg, least squares mean difference, -0.33 [standard error, 0.10], p < 0.001; 75mg, -0.28 [0.10], p=0.005; 100mg, -0.45 [0.15], p=0.003). LB-102 50mg (23.4%, p=0.001) and 75mg (17.6%, p=0.02) demonstrated significantly greater CGI-S remitter rates at the end of Week 4 compared to placebo (7.4%). Treatment-emergent adverse events (TEAEs) were reported in 56% (PBO), 69% (50mg), 57% (75mg), and 75% (100mg) of participants. Ten participants reported TEAEs leading to withdrawal (PBO, n=2; 50mg, n=2; 75mg, n=3; 100mg, n=3) and 5 reported serious TEAEs (PBO, n=2 [including 1 death]; each LB-102 arm, n=1).

Discussion

This phase 2 clinical trial provided robust evidence demonstrating the efficacy and safety of LB-102 for adults with acute schizophrenia, with greater PANSS total score responder and CGI-S remitter rates at the end of Week 4 compared to placebo.