JAMA Psychiatry
Novel antipsychotic shows symptom relief with fewer early adverse effects in phase 2 trial
Clinical takeaway: LB-102 shows clinically meaningful short‑term symptom reduction with a low burden of EPS and metabolic effects—supporting its potential role as a better‑tolerated dopamine antagonist pending phase 3 confirmation.
Managing acute schizophrenia often requires balancing symptom control against adverse effects that limit adherence. Benzamide antipsychotics have long been used outside the US for their efficacy, and LB‑102, an investigational agent in this class, was designed to build on that foundation while addressing prior tolerability and dosing limitations.
NOVA‑1 was a phase 2, multicenter, double‑blind randomized trial that evaluated the efficacy and safety of once‑daily, oral LB‑102 in adults hospitalized with acute schizophrenia. The US‑based study enrolled 359 adults aged 18 to 55 years and randomized them to LB‑102 50 mg, 75 mg, 100 mg, or placebo once daily for 4 weeks.
The trial met its primary endpoint: change in overall schizophrenia symptom severity from baseline to week 4, assessed using the Positive and Negative Syndrome Scale (PANSS), a 30‑item clinician‑rated measure designed specifically for schizophrenia. Mean PANSS total scores improved by 14.3 points with the 50‑mg dose and 14.0 points with the 75‑mg dose, compared with a 9.3‑point improvement with placebo (P<.001 and P=.002, respectively). The highest dose showed a larger numerical reduction (16.1 points) but was not included in the primary statistical testing hierarchy. Symptom separation from placebo emerged by week 1 and was sustained through week 4, with moderate effect sizes.
LB‑102 was generally well tolerated. Rates of extrapyramidal symptoms, akathisia, QTc changes, and sedation were low and comparable to placebo. Weight gain and prolactin elevations occurred infrequently, and serious adverse events were rare.
LB‑102 is now being evaluated in an ongoing phase 3, placebo‑controlled trial, with topline results anticipated in late 2027.
Sources:
Eramo, A, et al. (2026, April 22). JAMA Psychiatry. Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adults With Acute Schizophrenia: A Randomized Clinical Trial
LB Pharmaceuticals. (2026, April 22). Press release. LB Pharmaceuticals Announces Publication in JAMA Psychiatry of Results from Phase 2 NOVA-1 Trial of LB-102 in Schizophrenia