Iloperidone's efficacy and safety was also evaluated in this study in patients with specific genetic profiles using pharmacogenetics (PG), in order to potentially give physicians and patients information to help individualize their antipsychotic therapy. It had been previously identified that a certain polymorphism in a gene, occurring in approximately 70% of patients, may be associated with the pathogenesis of schizophrenia and 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 study that enrolled 604 patients with schizophrenia. The trial evaluated 12 mg of iloperidone 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 previous described genetic subpopulation.
The efficacy results 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
Using Last Observation Carried Forward (LOCF) methodology, iloperidone achieved statistical significance in both the primary and secondary endpoints. Iloperidone efficacy was also equal to the active control arm.
The study also evaluated 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. The study 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 results 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 very pleased with these results for iloperidone in this Phase III study", stated Louis R. Bucalo, Chairman, President and CEO of Titan Pharmaceuticals. "These results strongly support our position in the advancement of iloperidone".
The Phase III study was performed by Vanda Pharmaceuticals Inc. (Nasdaq: VNDA - News). Vanda acquired the rights to iloperidone from Titan's sublicensee, Novartis. Vanda plans to file an NDA for iloperidone by the end of 2007. Titan's agreements provide that Titan will receive a royalty of between 8-10% on worldwide sales of iloperidone.
About Schizophrenia
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.
About Titan Pharmaceuticals
Titan Pharmaceuticals, Inc. (AMEX:TTP - News) is a biopharmaceutical company focused on the development and commercialization of novel treatments for central nervous system disorders, cardiovascular disease, bone disease and other disorders. Titan's products in development utilize novel technologies that have the potential to significantly improve the treatment of these diseases. Titan also establishes partnerships with government institutions and other leading pharmaceutical development companies. For more information, please visit the Company's website at www.titanpharm.com.
The press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company's development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company's drug candidates, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug candidates that could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company's intellectual property or trade secrets and the Company's ability to obtain additional financing if necessary. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.
Contact: Titan Pharmaceuticals, Inc. Robert Farrell Executive Vice President & CFO 650-244-4990 or Media/Investors: The Trout Group Ian Clements, 415-392-3385
Source: Titan Pharmaceuticals, Inc.
