LB-102 for Schizophrenia Sees Positive Phase 2 Topline Results

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LB Pharmaceuticals just announced positive topline results from NOVA1, a phase 2 dose finding trial evaluating N-methyl amisulpride (LB-102), a once-daily orally administered novel dopamine D_2/3/5-HT₇ inhibitor and potential first-in-class benzamide antipsychotic, in adult patients with acute schizophrenia.^1,2

The study met its primary endpoint with LB-102 demonstrating statistically significant change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at 4 weeks. The 50 mg dose arm (n=107) achieved an effect size of 0.61 and participants experienced a 5.0-point reduction in PANSS total score when compared with placebo (P=0.0009). The 75 mg dose arm (n=108) achieved an effect size of 0.41 and participants experienced a 4.7-point reduction in PANSS total score when compared with placebo (P=0.0022). The exploratory dose of 100 mg (n=36) demonstrated an effect size of 0.83 and participants experienced a 6.8-point reduction in PANSS total score when compared with placebo (P=0.0017).

“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 US with acute schizophrenia,” said Heather Turner, chief executive officer of LB Pharmaceuticals. “Based on these findings, we plan to advance LB-102 into phase 3, explore its potential in additional psychiatric indications, and pursue the global development of a long-acting injectable formulation.”

In terms of safety profile, LB-102 was generally safe and well-tolerated. Participants experienced a low incidence of extrapyramidal symptoms (EPS), limited clinical adverse events associated with elevated prolactin, and minimal QT interval (QTcF) prolongation. In treated particpants, the average placebo-adjusted weight gain was 2 kg. Only 1 case of sedation was reported across 251 dosed participants. LB-102 is a methylated derivative of amisulpride, and as such, LB-102's emerging safety profile is favorable to amisulpride.

“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 3 treatment arms, underscoring the clinical and statistical strength of the efficacy findings,” said Anna Eramo, MD, chief medical officer of LB Pharmaceuticals. “We were pleased to see a generally safe and well-tolerated therapeutic profile across all 3 doses with a potential to further increase the dosage in future studies. Taken together, the strength of our findings in efficacy, safety, and tolerability underpins the potential of LB-102 to provide a much-needed treatment option for patients with schizophrenia.”

In terms of next steps, LB Pharmaceuticals intends to work with regulatory authorities to finalize phase 3 trial design. The phase 3 development program will likely be initiated late this year or early next year.

“Today, people living with schizophrenia frequently switch between medications in search of a treatment that adequately addresses their symptoms while being tolerable and safe for long term use. These data highlight the potential of LB-102 to provide a new option for patients in the US 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,” said John M. Kane, MD, professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, the codirector of the Institute for Behavioral Science at the Feinstein Institutes for Medical Research, and the principal investigator of NOVA1.

Investigators will present additional results from this study at upcoming scientific conferences in 2025.

References

1. LB Pharmaceuticals announces positive topline results from phase 2 trial of LB-102 in schizophrenia. News release. January 8, 2025. https://www.globenewswire.com/news-release/2025/01/08/3006104/0/en/LB-Pharmaceuticals-Announces-Positive-Topline-Results-from-Phase-2-Trial-of-LB-102-in-Schizophrenia.html

2. Wong DF, Chand GB, Caito N, et al. PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement. Neuropsychopharmacology. 2024;50(2):372-377.