title: Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia.
abstract: This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype.
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. .nisenbaum@lilly.com.
authors: Laura K
authors: LK
authors: Nisenbaum
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. downing_anncatherine_m@lilly.com.
authors: AnnCatherine M
authors: AM
authors: Downing
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. zhao_fangyi@lilly.com.
authors: Fangyi
authors: F
authors: Zhao
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. millen_brian_a@lilly.com.
authors: Brian A
authors: BA
authors: Millen
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. munsie_leanne_m@lilly.com.
authors: Leanne
authors: L
authors: Munsie
authors: Lundbeck LLC, Four Parkway North, Deerfield, IL 60015, USA. BKIN@lundbeck.com.
authors: Bruce J
authors: BJ
authors: Kinon
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. adams_david_henry@lilly.com.
authors: David H
authors: DH
authors: Adams
authors: Eli Lilly and Company, Indianapolis, IN 46285, USA. gomez_juan-carlos@lilly.com.
authors: Juan Carlos
authors: JC
authors: Gomez
authors: Computational Biology and Genomics, Biogen, 225 Binney Street, Cambridge, MA 02142, USA. michelle.penny@biogen.com.
authors: Michelle Ann
authors: MA
authors: Penny
keywords: HTR2A; pomaglumetad methionil; schizophrenia