Luvadaxistat

Neurocrine is halting further development of luvadaxistat after it failed to improve cognitive impairment in patients with schizophrenia in a mid-stage study . The company said in a Thursday update that luvadaxistat “failed to replicate the cognitive endpoints data” seen in a previous study because of “large variability” in cognitive abilities among the studied population. There was also an “imbalance in the baseline characteristics” of patients in the treatment arm, Neurocrine said. The hope was that the new data would validate previous Phase 2 results reported in 2021, which found luvadaxistat improved cognitive ability, the trial’s secondary endpoint. But the drug failed the primary endpoint of that trial, which was improvement in negative symptoms of schizophrenia. Negative symptoms describe schizophrenia patients withdrawing or isolating themselves from the world. Positive symptoms apply more to changes in behavior, like hallucinations. Luvadaxistat is now absent from the company’s pipeline, according to an updated R&D chart . Since Neurocrine will “halt further development of luvadaxistat at this time,” resources will instead go toward advancing two other neuropsychiatry candidates into Phase 3, CMO Eiry Roberts said in a statement. One such asset is NBI-1117568, which had a positive readout as a treatment for schizophrenia last month, albeit one that did not meet the company’s expectations. The company reported that the drug notched a 7.5-point improvement in schizophrenia symptoms compared to placebo, slightly less than the 8-point improvement that was hoped for. But the treatment paradigm in schizophrenia could potentially evolve in the next few years. Bristol Myers Squibb’s recently acquired KarXT is set for an FDA decision later this month and AbbVie is advancing a schizophrenia drug it got a hold of after buying Cerevel Therapeutics. Neurocrine expects to launch the Phase 3 study for NBI-’568 in early 2025. The company is also looking to advance its NBI-1065845 for major depressive disorder.

Concept art to depict schizophrenia and split personality disorder iStock, wildpixel BMO Capital Markets analyst Evan Seigerman said luvadaxistat’s inconsistencies between mid-stage trials raise questions about Neurocrine Biosciences’ developmental efforts moving forward. Neurocrine Biosciences on Thursday announced that it will no longer push through with the development of its investigational schizophrenia drug luvadaxistat after its disappointing mid-stage performance. The Phase II study, dubbed ERUDITE , was designed to evaluate luvadaxistat versus placebo in more than 200 schizophrenia patients with impaired cognition. The trial’s primary endpoint was cognitive improvement from baseline. Neurocrine did not provide specific figures in its announcement but said that luvadaxistat fell short of its primary endpoint in ERUDITE and was unable to “replicate the cognitive endpoints data seen in the earlier INTERACT study.” In the Phase II INTERACT trial, a 50-mg dose of luvadaxistat resulted in significant improvements in cognition, as assessed by two different tools. According to the biotech, INTERACT was “the first time statistical significance had been demonstrated for cognitive measure and function within a single study.” The company pinned ERUDITE’s failure on the “large variability” in cognitive measures across the study population, as well as a “potential imbalance” in the patients’ baseline characteristics. CMO Eiry Roberts in a statement called Thursday’s readout “disappointing,” noting that because of the failure Neurocrine will “halt further development of luvadaxistat at this time.” Instead, the company will focus resources on the Phase III development of its other neuropsychiatric assets, including NBI-1117568 in schizophrenia and NBI-1065845 in major depressive disorder. BMO Capital Markets analyst Evan Seigerman in a note to investors said that luvadaxistat’s inconsistency between trials raises important questions about Neurocrine. “We are left puzzled as to how baseline characteristics were left imbalanced,” Seigerman wrote, pointing out that “such a failing in trial construction makes us less optimistic for Neurocrine’s developmental efforts in an already notoriously tough indication.” Luvadaxistat’s failure and discontinuation will also add pressure on Neurocrine’s shares, though Seigerman expects the overall effect to be “minor” given that cognitive impairment associated with schizophrenia “was not an indication many investors were holding their breath for.” Thursday’s failure comes after the biotech reported late last month that another schizophrenia candidate, dubbed NBI-1117568, significantly improved symptoms in a Phase II study—though only at its lowest dose. All other strengths missed the primary endpoint. Investors were underwhelmed with these results and sent Neurocrine’s shares dropping 20% at the time. Earlier this year, Neurocrine scored a Phase II win for its investigational drug candidate NBI-1065845 in major depressive disorder, resulting in significant symptom reduction at 28 days versus placebo. NBI-1065845 is being developed with Takeda.