Phase 2 LB-102 Data, Advancing Treatment Landscape in Schizophrenia, with John Kane, MD

On January 8, 2025, LB Pharmaceuticals announced their phase 2 NOVA trial met its primary endpoint, demonstrating LB-102 significantly reduced Positive and Negative Syndrome Scale (PANSS) total scores over 4 weeks in adults with acute schizophrenia—setting the stage to advance the therapy to a phase 3 trial.

LB-102, a once-daily oral benzamide antipsychotic, targets both positive and negative symptoms and could become the first-in-class benzamide antipsychotic available in the US, according to the company release.

“The idea here was to enable a new chemical compound to be introduced into the US that would share some of the characteristics that we’ve seen with an existing compound that’s widely used outside of the united states," lead investigator John M. Kane, MD, professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, told HCPLive.

NOVA was a double-blind, placebo-controlled, multicenter trial that enrolled 359 adults aged 18–55 years with a DSM-5 diagnosis of acutely exacerbated schizophrenia. Participants were randomized 3:3:3:1 to receive placebo, 50 mg LB-102, 75 mg LB-102, or 100 mg LB-102 daily for 4 weeks. The primary endpoint was the change from baseline in PANSS total score at day 28 and secondary endpoints included improvements in CGI-S, PANSS subscales, Marder Factor scores, safety and tolerability, and pharmacokinetics.

Results showed significant reductions in PANSS total scores for LB-102 compared to placebo: 5.0 points for the 50 mg dose (effect size 0.61; P=.0009), 4.7 points for 75 mg (effect size 0.41; P=.0022), and 6.8 points for 100 mg (effect size 0.83; P=.0017).

According to the release from LB Pharmaceuticals, safety data were favorable, with minimal extrapyramidal symptoms, sedation reported by only one participant, and low adverse events linked to prolactin increase or QT prolongation. The average weight gain was 2 kg, which the release noted was comparable to amisulpride.

In the aforementioned release, LB Pharmaceuticals noted its plans to meet with regulatory authorities to finalize the phase 3 trial design, with the trial expected to begin in late 2025 or early 2026.

Relevant disclosures for Kane include Otsuka Pharmaceuticals, Sumitomo Pharmaceuticals, H. Lundbeck, Teva Pharmaceuticals, Alkermes, and Boehringer Ingelheim, among others.

References:

LB Pharmaceuticals Announces Positive Topline Results from Phase 2 Trial of LB-102 in Schizophrenia. Global Newswire. 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. Accessed January 8, 2025.