Amisulpride

LB Pharmaceuticals designed its phase 2 study to be considered a registrational trial. \n LB Pharmaceuticals has shared top-line data from a phase 2 schizophrenia trial, touting results that offer early support for its vision and putting it on track to start a pivotal study around the end of the year.The trial randomized 359 people with acutely exacerbated schizophrenia to receive one of three daily oral doses of LB-102 or placebo. LB-102 is a modified version of amisulpride, a dopamine inhibitor that was developed in the 1980s and marketed by Sanofi as a schizophrenia drug—Solian—outside the U.S. High doses of amisulpride are needed to achieve the optimum level of dopamine receptor occupancy.LB-102 could solve that limitation of amisulpride, enabling once-, rather than typically twice-, daily dosing while having superior efficacy and tolerability to the existing dopamine inhibitor and other drugs. The phase 2 trial represented a key test of that idea.LB Pharma saw statistically significant changes on the Positive and Negative Syndrome Scale (PANSS) after four weeks of treatment with all three tested doses of LB-102. Compared to placebo, patients on the low and middle doses of LB-102, respectively, had 5- and 4.7-point reductions in PANSS scores. The reduction in the smaller cohort that took the exploratory top dose was 6.8 points. Bristol Myers Squibb’s Cobenfy achieved an 8.4-point PANSS improvement over placebo after five weeks in a phase 3 trial that enrolled 256 people with schizophrenia experiencing acute psychosis. Neurocrine Biosciences saw placebo-adjusted improvements of up to 7.5 points in a phase 2 study of its would-be Cobenfy rival.Tolerability is central to LB Pharma’s pitch for the schizophrenia market, which is currently served by some drugs that are associated with side effects such as sedation and weight gain. Amisulpride is less prone to causing those side effects than other treatments. LB-102, like amisulpride, binds less to 5-HT2C, alpha-1 or H1 receptors than other treatments and could therefore enjoy the same tolerability benefits.LB Pharma saw one case of sedation across the 251 patients who took LB-102. Average placebo-adjusted weight gain was 2 kg. LB Pharma said the drug candidate’s safety profile was on par with amisulpride. The biotech will discuss the data in more detail at the J.P. Morgan Healthcare Conference next week and share more results later in the year. With phase 2 data in hand, LB Pharma plans to talk to regulators about starting a phase 3 trial late this year or early next year. The biotech designed the phase 2 study to be considered a registrational trial. There are also potential opportunities to study the lower dose of LB-102 in settings such as mood disorders.LB Pharma kept a fairly low profile in the past, raising funding from Deep Track Capital, TCG Crossover, Vida Ventures and Pontifax and moving through the clinic without making much noise. But the biotech has begun to speak up in recent months, publicizing its appointment of Heather Turner, who led Carmot Therapeutics to its $2.7 billion Roche buyout, as CEO and securing a slot at the J.P. Morgan event.

A private startup looking to bring an old schizophrenia drug class to the US has released new Phase 2 data and aims to start a pivotal trial this year. On Wednesday, LB Pharmaceuticals said its experimental treatment LB-102 improved patient symptoms compared with placebo in a schizophrenia rating score called the PANSS after four weeks. All three dose levels tested across 359 patients achieved statistical significance, the company said. It will next need to raise more money to run an additional study, CEO Heather Turner told Endpoints News , and that could come through either a private raise or an IPO. “We’d like to start with the private financing and see how that goes,” Turner said. “And then if the markets are there, we’ll do a public one as well.” LB-102 is a derivative of the antipsychotic medication amisulpride, which has been approved in some European countries since the 1990s. The drug was previously in development in the US: first by the French pharma company Synthélabo, and then by Sanofi after their 1999 merger. But Sanofi discontinued the drug in 2000 “based on IP” reasons, according to an LB investor deck from 2023 . At the time, the FDA had requested that researchers run an additional study. LB wants to bring an updated version of the drug to the US. LB-102 is in the same class as amisulpride — a dopamine D2 receptor antagonist — but modified slightly to add what’s known as a “methyl group,” lead trial investigator John Kane told Endpoints. That allows for easier penetration through the blood-brain barrier with a lower dose than amisulpride, curbing some side effects. “We have an opportunity to bring this medication to use in the US where, obviously, we have many patients with many unmet needs, many patients who change medications frequently,” Kane said. LB hopes the different class effects may help LB-102 eventually compete with Cobenfy, the recently approved schizophrenia drug from Bristol Myers Squibb. Cobenfy is the first new drug from its class of muscarinic receptor agonists, and Bristol Myers has played up that superlative in marketing the drug to schizophrenia patients. But the Phase 3 study for LB-102 will have to come first — and many schizophrenia drugs have failed at that phase after showing promising mid-stage data. Turner said the company is still deciding how it wants to design the trial and which of the three doses it wants to advance. The 50 mg dose induced a five-point reduction in the PANSS total score, the 75 mg dose coaxed a 4.7-point reduction, and the 100 mg dose saw a 6.8-point reduction. P-values for all of the dose arms were 0.0022 or below. LB last put together a funding round in January 2024, securing $75 million in a Series C, and has raised a total of about $122 million. The company had reportedly been considering an IPO as recently as June, but the public offering never materialized.