LB-102 Shows Promise in Reducing Acute Schizophrenia Symptoms: New Phase 2 Data

John M. Kane, MD

Credit: Northwell

LB Pharmaceuticals announced on January 8, 2025, that their phase 2 trial, NOVA, met its primary endpoint: LB-102 provided a statistically significant change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at 4 weeks.

LB-102, a once-daily oral drug, has the potential to be the first-in-class benzamide antipsychotic for US adult patients with acute schizophrenia. The drug targets both positive and negative symptoms of schizophrenia.

“These data highlight the potential of LB-102 to provide a new option for patients in the US [with schizophrenia] as the first-in-class benzamide antipsychotic with favorable efficacy, safety, and tolerability results and convenient once-daily dosing,” said lead investigator John M. Kane, MD, professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in a statement.

In NOVA, a phase 2, double-blind, placebo-controlled, multi-center inpatient trial, investigators sought to evaluate the efficacy and safety of LB-102 in 359 adults aged 18 – 55 years with a DSM-5 diagnosis of acutely exacerbated schizophrenia. The primary endpoint was the change from baseline in the PANSS total score at day 28, and secondary endpoints included improvement in CGI-S, PANSS subscale and Marder Factor scores, safety and tolerability, and pharmacokinetics. Participants were randomized 3:3:3:1 to receive a placebo, 50 mg LB-102, 75 mg LB-102, or 100 mg LB-102.

Compared with placebo, participants on 50 mg of LB-102 (n = 107) experienced a 5.0-point reduction in the PANSS total score (effect size of 0.61; P = .0009), and participants on the slightly higher dose of 75 mg (n = 108) had a 4.7-point reduction in the PANSS total score (effect size of 0.41; P = .0022). Participants on the exploratory dose of 100 mg (n = 36) had a 6.8-point reduction in the PANSS total score compared to placebo, with an effect size of 0.83 (P = .0017).

“We observed a clinically meaningful effect size across all three treatment arms, underscoring the clinical and statistical strength of the efficacy findings,” said Anna Eramo, MD, chief medical officer of LB Pharmaceuticals, in the press release.

LB-102 was safe and well-tolerated, with low extrapyramidal symptoms, adverse events linked to increased prolactin, and QT interval prolongation. Only 1 participant on LB-102 reported sedation.

The mean weight gain was 2 kg or 4.4 lb. The safety profile of LB-102 is comparable to amisulpride, a drug considered 1 of the best-tolerated antipsychotics. LB-102 is a methylated derivative of amisulpride.

“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,” Kane said.

LB Pharmaceuticals plans to meet with regulatory authorities to finalize the phase 3 trial design, hoping to start the phase 3 trial in late 2025 or early 2026.

“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,” Eramo said.

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.}