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Phase 3 Trial Evaluating Iloperidone Demonstrates Improvement Compared to Placebo
Vanda also evaluated iloperidone's efficacy and safety in patients with specific genetic profiles using its expertise in pharmacogenetics (PG), as part of its commitment to give physicians and patients information to help personalize their antipsychotic therapy. Vanda had previously identified a polymorphism in a gene, occurring in approximately 70% of patients, hypothesized to be associated with the pathogenesis of schizophrenia which appeared to correlate with iloperidone response. Iloperidone achieved statistical significance vs. placebo on the PANSS scale in these patients, with a magnitude of response greater than that seen in the overall iloperidone population.
The Phase III trial was a randomized, double-blind, placebo-controlled, multi-center, 4 week inpatient study that enrolled 604 patients with schizophrenia. The trial examined iloperidone 12 mg dosed twice-daily, or 24 mg per day. The primary endpoint was efficacy vs. placebo in PANSS (total) using the Mixed Method Repeated Measures (MMRM) methodology. The secondary endpoint was efficacy in the genetic subpopulation.
The specific findings of efficacy vs. placebo include:
* Efficacy (intent to treat population):
* PANSS (total): p=0.006
* PANSS (positive symptoms only): p=0.0009
* PANSS (negative symptoms only): p=0.027
* Brief Psychiatric Rating Scale (BPRS): p=0.0128
* Efficacy (genetic subpopulation):
* PANSS (total): p=0.002
Under Last Observation Carried Forward (LOCF) methodology, iloperidone met the primary and secondary endpoints with statistical significance. Iloperidone efficacy was also equal to the active arm.
Vanda also measured the effect of iloperidone on the QT interval, a well understood atypical antipsychotic class side effect. The mean QT prolongation was consistent with previous experience. No patients experienced QT intervals in excess of 500 milliseconds, a threshold of concern to the FDA. Vanda also confirmed with an additional genetic marker that the QT prolongation was shorter in the majority of patients who are good iloperidone metabolizers.
The specific findings include:
* QTc change from baseline:
* All patients: 11.4 milliseconds (msec)
* Good metabolizers: 10.4 msec
* Poor metabolizers: 15.0 msec (p=0.008, good vs. poor)
"We are extremely pleased to have achieved this outcome with iloperidone. The success of this trial moves us one step closer to our NDA filing, expected in late 2007, and one step closer to making iloperidone available to patients and providers dealing with schizophrenia," stated Paolo Baroldi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Vanda.
"We are especially pleased to have achieved our pharmacogenetic results," stated Mihael Polymeropoulos, M.D., President and CEO of Vanda. "For the first time in the treatment of a psychiatric disease, we have applied pharmacogenetic tools to identify patients best suited for a specific drug therapy. Our market research indicates that physicians treating schizophrenia patients would enthusiastically welcome such information in making prescribing decisions. We are committed to further exploration, after iloperidone approval, to identify the genetic basis of many aspects of iloperidone response."
Schizophrenia is a chronic, debilitating mental disorder characterized by hallucinations, delusions, racing thoughts and other psychotic symptoms (collectively referred to as "positive symptoms"), as well as moodiness, anhedonia (inability to feel pleasure), loss of interest, eating and sleep disturbances, and difficulty concentrating (collectively referred to as "negative symptoms"). Schizophrenia develops in late adolescence or early adulthood in approximately 1% of the world's population. Genetic and environmental factors are believed to be responsible for the disease.
Source: Vanda Pharmaceuticals Inc