Genetic Variation Associated With Treatment Response In A Clinical Study Of A New Atypical Antipsychotic Fiaptatm (iloperidone)

A study reported in the journal Pharmacogenomics suggests that a genetic variation in the Ciliary Neurotrophic Factor gene (CNTF) may affect response to antipsychotic treatment. The study, conducted by Vanda Pharmaceuticals Inc., included patients with acute symptoms of schizophrenia who were treated either with Fiapta(TM) (iloperidone), a novel atypical antipsychotic agent currently under review with the FDA, or placebo. Patients were also studied for a genetic variation in the CNTF gene. CNTF is a neurotrophic factor important for neuronal survival and recovery after injury. About 75% of the population carry two intact copies of the CNTF protein while 25% carry one or two truncated copies of the protein.

As previously reported in the clinical study overall, it was shown that Fiapta(TM) was significantly more effective than placebo in treating both the positive and negative symptoms of schizophrenia. In addition, Fiapta(TM) showed significant improvement from baseline in all symptoms across all patient genotypes of CNTF.

In the patient population carrying both intact copies of CNTF (representing 75% of the population), Fiapta(TM) treatment was significantly better than placebo in symptom improvement. In patients carrying at least one truncated copy of the CNTF protein, placebo and Fiapta(TM) treated patients had a significant improvement from baseline indicating an enhanced placebo response among this group of patients.

"This is a pioneering effort in understanding why some people respond to antipsychotic medication and others do not. The results of this prospective study on the genetics of drug response offer tantalizing clues on the involvement of neurotrophic factors in schizophrenia," said Steven G. Potkin, MD, Professor of Psychiatry, Robert R. Sprague Chair in Brain Imaging, and Director, Clinical Psychiatric Research at the University of California, Irvine.

These findings suggest that neurotrophic factors like CNTF and genetic variations within them may play important roles in antipsychotic response and the course of illness of patients with schizophrenia. "This study is an important first step towards understanding the role of genetic variation in antipsychotic treatment response and eventually the introduction of personalized medicine in the treatment of schizophrenia," noted Dr. Anil Malholtra, MD, Director, Division of Psychiatry Research, The Zucker Hillside Hospital.