LB-102 Significantly Improves Disease Severity in Acute Schizophrenia, with John Kane, MD

LB Pharmaceuticals announced additional positive data from NOVA, a phase 2 study evaluating LB-102 in acute schizophrenia, at the 2025 Annual Congress of the Schizophrenia International Research Society held in Chicago from March 29 to April 2.1 LB-102 provided significant improvement in disease severity, as demonstrated by the mean change from baseline in Clinical Global Impression of Severity (CGI-S) scores.

At week 4, participants on 50 mg of LB-102 (n = 107) achieved a mean change in baseline CGI-S score of -0.72 compared with placebo (P = .0008). For LB-102 doses 75 mg (n = 108) and 100 mg (n = 36), participants achieved a mean change in CGI-S from baseline of -0.67 (P = .00048) and -0.84 (P = .0026), respectively.

This announcement followed the company’s previous announcement on January 8, 2025, stating that NOVA met its primary endpoint, with LB-102 significantly reducing the Positive and Negative Syndrome Scale (PANSS) total scores over 4 weeks in adults with acute schizophrenia compared to placebo.2

Already, LB-102, a once-daily oral benzamide antipsychotic targeting both positive and negative symptoms, was evaluated in NOVA, a double-blind, placebo-controlled, multicenter trial with 359 adults aged 18 – 55 years who had a DSM-5 diagnosis of acutely exacerbated schizophrenia. NOVA’s primary endpoint was the change from baseline in the PANSS total score at day 28, and secondary endpoints included improvements in CGI, PANSS subscales, Marder Factor scores, safety and tolerability, and pharmacokinetics. Participants were randomized 3:3:3:1 to receive placebo or LB-102 at daily doses of 50 mg, 75 mg, or 100 mg for 4 weeks.

HCPLive recently spoke with lead investigator John M. Kane, MD, professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, about the new data on improved CGI-S scores.

“This is another perspective that helps clinicians evaluate the efficacy of a medication, and the PANSS total score reflects results on specific items, and the CGI is really a measure of overall severity,” Kane explained. “And so, we see patients moving from one level of severity to a lower level…That's a very good clinical indicator.”

During the interview, Kane provided insight into the tolerability of LB-102 compared to 6 existing psychotics in terms of prolactin levels, weight gain, and extrapyramidal symptoms. Some patients on LB-102 experienced increased prolactin levels, but despite this, very few led to breast enlargement or erectile dysfunction. Very few patients experienced extrapyramidal symptoms, and while some experienced weight gain, it was not a lot.

When asked in what scenarios Kane might recommend LB-102 over current first—or second-line agents, he said it depends on trial results. LB-102 had already been successful as a first-line agent in trial participants.

People can also try LB-102 if they do not respond to other drugs. There are no current medications to treat negative symptoms of schizophrenia, so research may find LB-102 could manage these symptoms.

“We're also thinking about the maintenance effects, what are the characteristics of this medication over time, in terms of patient improvement, acceptability, and continuation,” Kane said. “…to me, that's really important. Most patients will be candidates to continue an antipsychotic medication for long periods of time, and how the drug performs over time is going to be very important. From what we've seen with amisulpride…the possibilities for LB-102 are very encouraging.”

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

References

1. LB Pharmaceuticals Presents New Data from Phase 2 Clinical Trial of LB-102 at the 2025 Annual Congress of the Schizophrenia International Research Society. GlobeNewswire. March 31, 2025. https://www.globenewswire.com/news-release/2025/03/31/3052289/0/en/LB-Pharmaceuticals-Presents-New-Data-from-Phase-2-Clinical-Trial-of-LB-102-at-the-2025-Annual-Congress-of-the-Schizophrenia-International-Research-Society.html. Accessed April 11, 2025.

2. Derman, C. Phase 2 LB-102 Data, Advancing Treatment Landscape in Schizophrenia, with John Kane, MD. HCPLive. January 10, 2025. https://www.hcplive.com/view/phase-2-lb-102-data-advancing-treatment-landscape-in-schizophrenia-with-john-kane-md. Accessed April 11, 2025.