Neurocrine Biosciences’ schizophrenia program pivot has failed. The biotech was unable to replicate the cognition signal it saw in an earlier midphase study, prompting it to stop development of luvadaxistat.
San Diego-based Neurocrine in-licensed the DAAO inhibitor luvadaxistat and other R&D programs from Takeda for $120 million upfront in 2020. The next year, a phase 2 trial of luvadaxistat missed its primary endpoint. However, while the candidate failed to improve schizophrenia symptoms on the PANSS scale, Neurocrine did track a significant improvement on secondary endpoints that looked at cognition.
The secondary endpoint wins persuaded Neurocrine to run a second phase 2 trial that largely replicated the design of the earlier study. The key difference was the use of the Brief Assessment of Cognition in Schizophrenia as the primary endpoint. Neurocrine included another cognition scale as a secondary goal.
This time around, the biotech failed to replicate the cognitive data seen in the earlier trial. Neurocrine said the failure was partly caused by “the large variability seen in the cognitive measures across the population studied and a potential imbalance in the baseline characteristics of subjects enrolled across the treatment arms.”
Rather than try to address those issues in a third trial, the biotech has decided to stop development of the drug candidate and focus its resources on other assets. Specifically, Neurocrine plans to pump the money into phase 3 studies of NBI-1117568 for schizophrenia and NBI-1065845 for major depressive disorder.
Neurocrine’s share price fell 2% to below $119 in premarket trading, a muted reaction that likely reflects expectations for the program. William Blair analysts said they “viewed luvadaxistat development as high risk” in a note published in response to the failed trial. Neurocrine was open about the risks in the run-up to the readout, too.
“Cognitive impairment associated with schizophrenia has been a very, very challenging area. It's about as high risk as you could get, in my view, and there's not a lot known about clinical development in this space because there's such a few number of companies that have worked here,” Kyle Gano, Ph.D., chief business development and strategy officer at Neurocrine, said at a Wells Fargo event last week.
There are no FDA-approved treatments for cognitive impairment associated with schizophrenia. Biogen, Roche and Pfizer have studied candidates in the setting but no longer have any active trials. Recognify Life Sciences, an atai Life Sciences company, is running a phase 2 trial that is scheduled to end this year, according to ClinicalTrials.gov.