Summary

LB-102 is investigational and has no established place in therapy. LB Pharmaceuticals states that LB-102 has the potential to be the first benzamide antipsychotic approved for neuropsychiatric disorders in the United States and describes it as a potential alternative to branded and generic therapeutics for schizophrenia. The parent compound, amisulpride, is approved in more than 50 countries excluding the United States; the company reports that Sanofi announced in 2000 that it would not pursue U.S. approval for schizophrenia. The company expects to commercialize the oral formulation where amisulpride is unavailable as a generic and a long-acting injectable formulation worldwide.

The studied setting is acute inpatient care. NOVA-1 randomized 359 participants at 25 U.S. inpatient sites to 28 days of inpatient treatment, and its authors state that further studies are needed to assess whether the findings generalize to outpatients and that the trial was not designed to evaluate long-term durability. The company describes NOVA-2 as the pivotal phase 3 trial and NOVA-3 as an outpatient open-label trial that accrues the safety population for the NDA. Long-term outpatient maintenance use is therefore anticipated and has no controlled evidence yet.

Guidelines do not rank agents. The APA guideline states that an evidence-based ranking of antipsychotics is not possible and notes no preference between generations, the VA/DoD guideline bases the choice on patient characteristics and side effect profiles, and a 2026 Australian and New Zealand guideline names aripiprazole, brexpiprazole, cariprazine, and lurasidone as first-line agents and lists amisulpride among agents to consider second. Evidence for amisulpride comes from European trials and network meta-analysis: amisulpride had the largest standardized mean difference against placebo for positive symptoms (−0.69) among the 17 agents with a significant reduction, and the authors note that no placebo-controlled amisulpride study was available, which makes that evidence indirect; in EUFEST, 12-month all-cause discontinuation was 40% with amisulpride and 72% with haloperidol; in OPTiMiSE, 250 of 446 participants (56%) achieved remission on open-label amisulpride; and in BeSt InTro, the 52-week PANSS reduction was 32.7 points with amisulpride, 21.9 with aripiprazole, and 23.3 with olanzapine. The company reports at least two million monthly amisulpride prescriptions in 2023 in 16 continental European countries. Amisulpride is among the agents with the highest reported rates of hyperprolactinemia.

Company positioning: first benzamide antipsychotic in the United States

“We are building a pipeline that leverages the broad therapeutic potential of our lead product candidate, LB-102, which we believe has the potential to be the first benzamide antipsychotic drug approved for neuropsychiatric disorders in the United States.” (opens the source at this quote in a new tab)
“We believe that LB-102, if approved, can become a mainstay of psychiatric practice by offering a potentially attractive alternative to branded and generic therapeutics for the treatment of schizophrenia, bipolar depression, adjunctive MDD and other neuropsychiatric diseases, given the compelling balance of clinical activity and tolerability observed to date.” (opens the source at this quote in a new tab)

Company positioning in the 2025 initial public offering prospectus

“We believe that LB-102, if approved, can become a mainstay of psychiatric practice by offering a potentially attractive alternative to branded and generic therapeutics for the treatment of schizophrenia, bipolar depression, and other neuropsychiatric diseases.” (opens the source at this quote in a new tab)

Agents the company describes as first-line treatments in the United States

“This analysis also found that amisulpride was 20% more effective at reducing overall symptoms of schizophrenia compared to risperidone, which is a first-line treatment for schizophrenia in the United States.” (opens the source at this quote in a new tab)
“A 2020 Lancet Psychiatry report of a head-to-head long-term study showed amisulpride to have greater reduction in PANSS total score from baseline compared to first-line treatments of aripiprazole and olanzapine.” (opens the source at this quote in a new tab)

Company-stated target profile

“We believe a treatment that is effective, tolerable, supports adherence in a fragile population and can address negative and residual symptoms could become a mainstay of schizophrenia treatment.” (opens the source at this quote in a new tab)
“We believe LB-102 has the potential to meet this profile.” (opens the source at this quote in a new tab)

Amisulpride: approval outside the United States

“Amisulpride is a dopamine receptor antagonist originally developed in France in the 1980s and is approved in more than 50 countries worldwide (not including the United States) for the treatment of schizophrenia and, in certain countries outside of the United States, for the treatment of dysthymia, a form of depression, and predominantly negative symptoms of schizophrenia.” (opens the source at this quote in a new tab)
“In 2000, Sanofi S.A., the manufacturer of Solian, the branded version of amisulpride, announced it would not pursue approval for schizophrenia in the United States because the development and regulatory requirements of the FDA were incompatible with its patent coverage on the drug.” (opens the source at this quote in a new tab)

Amisulpride: company-reported use in Europe

“Amisulpride is a generic drug that has been extensively used in clinical practice following its initial approval in France in the 1980s, generating at least two million monthly prescriptions in 2023 in a subset of 16 continental European countries.” (opens the source at this quote in a new tab)
“Among these European prescriptions for amisulpride, our data suggest that approximately 60% are for schizophrenia and schizoaffective disorders, approximately 20% are for mood disorders, approximately 14% are for anxiety, and the remainder are for a variety of other indications.” (opens the source at this quote in a new tab)

Planned commercialization by formulation

“If approved for schizophrenia, we expect to commercialize the oral formulation of LB-102 in jurisdictions where amisulpride is unavailable as a generic, and we expect to commercialize an LAI form of LB-102 worldwide.” (opens the source at this quote in a new tab)

Studied setting: inpatient acute treatment in NOVA-1

“conducted at 25 inpatient sites in the US between December 2023 and August 2024.” (opens the source at this quote in a new tab)
“The inpatient setting minimized risks related to nonadherence, illicit substance use, and unauthorized concomitant medications; further studies are needed to assess whether these findings are generalizable to an outpatient population.” (opens the source at this quote in a new tab)
“was conducted over 4 weeks and was not designed to evaluate the long-term durability of treatment.” (opens the source at this quote in a new tab)

Phase 3 and outpatient open-label trials

“LB-102 is currently in late-stage clinical development for schizophrenia (pivotal Phase 3 NOVA-2 trial) and bipolar depression (Phase 2 ILLUMINATE-1 trial).” (opens the source at this quote in a new tab)
“we are enrolling an outpatient, open label trial (NOVA-3) to accrue the requisite safety population required to support NDA submission” (opens the source at this quote in a new tab)

“Doses selected to inform use in commercial setting” (opens the source at this quote in a new tab)
“~900 patients – rollover from Phase 3 trial + new patients” (opens the source at this quote in a new tab)

Amisulpride in European randomized trials

“Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57])” (opens the source at this quote in a new tab)

“Of the 446 patients in the intention-to-treat sample, 371 (83%) completed open-label amisulpride treatment, and 250 (56%) achieved remission after phase 1.” (opens the source at this quote in a new tab)

“After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025).” (opens the source at this quote in a new tab)
“We observed weight gain and increases of serum lipids and prolactin in all groups.” (opens the source at this quote in a new tab)

Amisulpride in the network meta-analysis of 32 antipsychotics

“Amisulpride was among the most efficacious antipsychotics, but no placebo-controlled study was available, making this evidence entirely indirect.” (opens the source at this quote in a new tab)
“The SMDs for the 17 (81%) drugs that significantly reduced positive symptoms compared with placebo ranged between −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole” (opens the source at this quote in a new tab)

Amisulpride in a 2026 guideline

“Certain medications, such as cariprazine, aripiprazole and low-dose amisulpride, may offer greater efficacy for negative symptoms and antidepressant augmentation may be helpful for some” (opens the source at this quote in a new tab)

Recommendations on benzamide antipsychotics in United States guidelines

No evidence found.