Neurocrine looks for the silver linings in schizophrenia failure

When in doubt pivot. Today’s mid-stage failure of Neurocrine Biosciences/Takeda’s luvadaxistat in schizophrenia negative symptoms, while disappointing, might not spell the end of the road for this project. The phase II Interact study missed its primary endpoint, changes in the PANSS NSFS score from baseline; however, two secondary endpoints concerning cognitive assessment were nominally positive, the companies said. Given this outcome and the unmet need in treating negative schizophrenia symptoms, Neurocrine and Takeda are expected to press on with luvadaxistat, which is thought to increase NMDA activity and thereby address the NMDA receptor hypofunction that has been linked with schizophrenia symptoms. Still, today’s setback is unlikely to dispel concerns about the NMDA hypothesis, which also took a blow in February with the failure of Concert Pharmaceuticals’ CTP-692. Stifel analysts said the two molecules addressed different patient populations and worked differently – CTP-692 is a deuterated form of D-serine, a co-agonist of the NMDA receptor, while luvadaxistat inhibits D-amino acid oxidase, the enzyme that breaks down D-serine. Neurocrine, which signed its deal with Takeda over luvadaxistat last June, saw its stock fall 6% this morning.

Neurocrine's clinical pipeline
Project Indication Description Note
Phase III
Crinecerfont (NBI-74788) Congenital adrenal hyperplasia CRF1 antagonist Ph3 in adults (NCT04490915), ph2 in children (NCT04045145)
Phase II  
Luvadaxistat (NBI-1065844/TAK-831)* Negative symptoms of schizophrenia D-amino acid oxidase inhibitor Ph2 Interact study failed Mar 2021
NBI-827104 (ACT-709478)** Rare paediatric epilepsy (CSWS) T-type  calcium channel blocker  Ph2 (NCT04625101) completes Dec 2021
Phase I  
NBI-921352 (XEN901)^ Rare paediatric epilepsy (SCN8A-DEE) & adult focal onset seizures NaV 1.6 sodium channel blocker Ph2 to start in 2021
NBI-1065845/TAK-653* Treatment-resistant depression Ampa potentiator Ph2 to start in 2021
NBI-1065846/TAK-041* Anhedonia in depression GPR139 agonist Ph2 to start in 2021
CSWS = epileptic encephalopathy with continuous spike and wave during sleep. SCN8A-DEE = SCN8A developmental and epileptic encephalopathy. *Under Takeda collaboration; **licensed from Idorsia; ^licensed from Xenon. Source: EvaluatePharma & company presentation.

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