LB Pharmaceuticals has announced positive topline results from its Phase 2 NOVA1 trial, evaluating LB-102 in adult patients with acute schizophrenia. The study, involving 359 participants, met its primary endpoint by demonstrating a statistically significant change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at 4 weeks across all dose levels compared to placebo.
The NOVA1 trial was a randomized, double-blind, placebo-controlled, multi-center inpatient study. It enrolled adults aged 18 to 55 with a DSM-5 diagnosis of acutely exacerbated schizophrenia. Participants were randomized to receive either placebo, 50 mg, 75 mg, or 100 mg of LB-102 once daily.
Efficacy and Safety Results
The 50 mg dose arm (n=107) achieved an effect size of 0.61, with participants experiencing a 5.0-point reduction in PANSS total score compared to placebo (p=0.0009). The 75 mg dose arm (n=108) achieved an effect size of 0.41, leading to a 4.7-point reduction in PANSS total score compared to placebo (p=0.0022). An exploratory 100 mg dose (n=36) demonstrated an effect size of 0.83, with a 6.8-point reduction in PANSS total score compared to placebo (p=0.0017).
LB-102 was generally safe and well-tolerated. Subjects experienced a low incidence of extrapyramidal symptoms (EPS), limited clinical adverse events associated with elevated prolactin, and minimal QT interval (QTcF) prolongation – adverse events commonly associated with D2 antagonists. The average placebo-adjusted weight gain for treated subjects was 2 kg. Across 251 dosed subjects, only one case of sedation was reported.
Potential as a First-in-Class Treatment
LB-102, a methylated derivative of amisulpride, is being developed as a potential first-in-class benzamide antipsychotic in the U.S. Heather Turner, Chief Executive Officer of LB Pharmaceuticals, stated, "The efficacy, safety, and tolerability data observed in this study reinforce the potential of LB-102 to provide a first-in-class benzamide option for patients in the U.S. with acute schizophrenia." The company plans to advance LB-102 into Phase 3 trials and explore its potential in additional psychiatric indications, as well as the development of a long-acting injectable formulation.
Anna Eramo, M.D., Chief Medical Officer of LB Pharmaceuticals, noted, "This trial, designed to be considered a registrational trial in both size and statistical powering, provided high-quality data to inform our clinical path forward. We observed a clinically meaningful effect size across all three treatment arms, underscoring the clinical and statistical strength of the efficacy findings."
Expert Commentary
John M. Kane, M.D., Professor of Psychiatry and Molecular Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, and the Principal Investigator of NOVA1, commented, "These data highlight the potential of LB-102 to provide a new option for patients in the U.S. as the first-in-class benzamide antipsychotic with favorable efficacy, safety and tolerability results and convenient once-daily dosing. The safety profile of the 50 mg dose creates an opportunity to explore other settings where typically lower doses of antipsychotics are indicated, such as for mood disorders and as a long-acting injectable formulation."
Next Steps
LB Pharmaceuticals plans to engage with regulatory authorities to finalize the Phase 3 trial design and expects to initiate the Phase 3 development program late this year or early next year. Additional results from this study will be presented at upcoming scientific conferences in 2025.
