Navigation Links
Data Presented at the American Psychiatric Association (APA) Annual Meeting Demonstrate Iloperidone's Efficacy and Safety, With Low Rates of Movement and Metabolic Adverse Events

Pharmacogenetic Findings May Lead to Individualized Treatment for


WASHINGTON, MAY 6 /PRNewswire-FirstCall/ -- Data presented today on Vanda Pharmaceuticals Inc.'s (Nasdaq: VNDA) investigational drug candidate, iloperidone, included its 4-week, short-term Phase III trial, as well as a pooled analysis of three long-term, 52-week trials, studying the efficacy and safety of iloperidone. Iloperidone is a 5HT2/D2 antagonist ("atypical") antipsychotic currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia. Additional data were presented identifying genetic markers that may help predict response to iloperidone, which Vanda believes could lead to unique, individualized treatment for schizophrenia. These data were presented today at the 161st American Psychiatric Association (APA) Annual Meeting in Washington, D.C.

"The data from the clinical trials studying the efficacy and safety of iloperidone suggest that iloperidone could be a useful long-term treatment option for people with schizophrenia," said Peter Weiden, M.D., Director of the Psychosis Program of the Department of Psychiatry at the University of Illinois at Chicago and one of the leading experts on adverse events of antipsychotic medications.

The data presented are part of the New Drug Application (NDA) submitted and currently under review by the FDA and demonstrate that iloperidone is effective in the short-term treatment of schizophrenia and that iloperidone is non-inferior to haloperidol in long-term maintenance measured as time to relapse over 52 weeks. In these trials, iloperidone showed short- and long- term safety with respect to movement disorders and metabolic effects, including extrapyramidal symptoms (EPS) and akathisia, as well as blood glucose, body weight and lipid profiles.

Schizophrenia is a chronic, severe and disabling disorder that affects approximately one percent of Americans. A high degree of treatment dissatisfaction remains among patients with schizophrenia and the physicians who treat them. The recent CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, conducted by the National Institute of Mental Health (NIMH) and reported in the New England Journal of Medicine, evaluated several antipsychotic medications and revealed that 74 percent of patients taking antipsychotics discontinued treatment within 18 months, primarily because of insufficient efficacy and tolerability issues(*).

Iloperidone's Efficacy Profile

In data presented on a 4-week Phase III trial, iloperidone (24 mg/day) was more effective than placebo in the short-term treatment of acutely exacerbated schizophrenia, providing relief across both positive and negative symptom domains. Iloperidone showed significantly greater improvement than placebo in PANSS-T(1) scores, as did ziprasidone (-12.0; p=0.006 for iloperidone vs. placebo and -12.3; p=0.012 for ziprasidone vs. placebo); these improvements were seen in both the mean PANSS-P and PANSS-N(2) subscales. Additionally, BPRS(3) scores improved significantly with iloperidone (-7.4; p=0.013) and ziprasidone (-7.2; p=0.042) versus placebo; and CGI-S(4) scores also significantly improved with iloperidone (-0.65; p=0.007) and ziprasidone (-0.67; p=0.013) versus placebo(1).

In data presented from three prospective, 52-week Phase III trials comparing a dose range of iloperidone (4-16 mg/day given BID, n=981) to haloperidol (5-20 mg/day given BID, n=300), iloperidone was statistically non- inferior to haloperidol in time to relapse (89.8 days with iloperidone vs. 101.8 days with haloperidol; p=0.764). Additionally, the three trials found similar relapse rates and improvements in CGI-C(5) and PANSS-T scores.

Iloperidone's Safety Profile

Data presented from a 4-week Phase III trial demonstrated that rates of worsened BAS(6) total score was similar between iloperidone and placebo (8.3% vs. 11.6%; p=0.302) but significantly higher with ziprasidone versus placebo (26.0% vs. 11.6%; p<0.01). Iloperidone also showed significant improvements versus placebo on six ESRS(7) subscales (p<0.05), while ziprasidone was associated with improvements over three ESRS subscales (p<0.05). The incidence of treatment-emergent EPS was 3.0% in the iloperidone group, 2.0% in the placebo group and 9.3% in the ziprasidone group. On average, no patients in either treatment group had clinically meaningful increases in metabolic parameters such as blood glucose, body weight, total cholesterol, triglycerides, or prolactin elevation(3).

In data presented from three 52-week Phase III trials, comparing a dose range of iloperidone (4-16 mg/day given BID) to haloperidol (5-20 mg/day given BID), iloperidone demonstrated significant improvements in EPS at endpoint, as measured by ESRS, versus haloperidol (-1.6 vs. 0.6; p<0.001); and a significantly lower percentage of patients on iloperidone experienced worsening EPS (13.5% for iloperidone vs. 36.4% for haloperidol; p<0.001) and akathisia (9.2% for iloperidone vs. 23.7% for haloperidol; p<0.001). There were no clinically meaningful changes in serum cholesterol, glucose, or triglycerides. Mean weight increases were 2.6 and 0.6 kg for iloperidone and haloperidol during the 6-week phase and an additional weight gain of 1.2 and 1.7 kg was observed at endpoint for iloperidone and haloperidol, respectively.

Study of Genetic Markers to Predict Likelihood of Response to Iloperidone

Pharmacogenetic analysis in a Phase III trial studying the efficacy of iloperidone in acute schizophrenia identified six single nucleotide polymorphisms (SNPs) associated with efficacy of iloperidone.

-- The highest specificity and positive predictive value were observed

with rs11851892 (NPAS3) with a change from baseline to endpoint PANSS-T

score of -20.12 (p=0.000093)

-- The highest sensitivity and negative predictive value were seen with

rs9643483 (XKR4) with a change from baseline to endpoint PANSS-T score

of -15.02 (p=0.00017)

-- None of the six SNPs was significantly associated with response to


The combination of six markers defined several groups of patients with different probability of response to iloperidone. Twenty-seven percent of patients carried at least five of the most favorable genotypes and constituted a group of iloperidone responders who showed a response of greater magnitude and of an earlier onset as compared to patients with alternative genetic make- up. These genetic markers for iloperidone response were not correlated to prediction of ziprasidone response. These results, while requiring further confirmation, are encouraging and suggest that pharmacogenetics may have the potential to identify likely responders and differentiate antipsychotics.

"Whenever a new antipsychotic becomes available, it may be possible to help some of our patients who had not responded well to other available medications," said Dr. Weiden. "Based on my experience, individual patients may have very different responses to individual antipsychotics and one of the frustrating parts of trying new medications is that we have no good way of knowing in advance which patient will respond well to a medication. Research to help clinicians determine whether one medication might work better than another for a patient would be a big advancement."

"Pharmacogenetics research to help identify markers of schizophrenia treatment response is fundamental and may help usher us into an era of personalized treatments in schizophrenia and bring us one step closer to providing the optimal treatment for each patient," said Paolo Baroldi, M.D., Ph.D., Chief Medical Officer, Vanda Pharmaceuticals Inc.

About Vanda Pharmaceuticals Inc.

Vanda Pharmaceuticals Inc. is a biopharmaceutical company focused on the development and commercialization of clinical-stage product candidates for central nervous system disorders. The company has three product candidates. Vanda's lead product candidate, iloperidone, is under clinical investigation for the treatment of schizophrenia, but has not been approved by any regulatory authority. The FDA accepted Vanda's iloperidone New Drug Application (NDA) for filing in November 2007 and Vanda expects a decision from the FDA on or about July 27, 2008. Vanda's second product candidate, tasimelteon (VEC-162), is a compound for the treatment of sleep and mood disorders, which is currently in Phase III for chronic primary insomnia. Vanda's third product candidate, VSF-173, is a compound for the treatment of excessive sleepiness in Phase II. For more on Vanda Pharmaceuticals Inc., please visit

Cautionary Note Regarding Forward-Looking Statements

Various statements in this release are "forward-looking statements" under the securities laws. Words such as, but not limited to, "believe," "expect," "anticipate," "estimate," "intend," "plan," "targets," "likely," "will," "would," and "could," and similar expressions or words, identify forward- looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Vanda is at an early stage of development and may not ever have any products that generate significant revenue. Important factors that could cause actual results to differ materially from those reflected in the company's forward-looking statements include, among others: delays in the completion of Vanda's clinical trials; a failure of Vanda's product candidates to be demonstrably safe and effective; Vanda's failure to obtain regulatory approval for its products or to comply with ongoing regulatory requirements; a lack of acceptance of Vanda's product candidates in the marketplace, or a failure to become or remain profitable; Vanda's inability to obtain the capital necessary to fund its research and development activities; Vanda's failure to identify or obtain rights to new product candidates; Vanda's failure to develop or obtain sales, marketing and distribution resources and expertise or to otherwise manage its growth; a loss of any of Vanda's key scientists or management personnel; losses incurred from product liability claims made against Vanda; a loss of rights to develop and commercialize Vanda's products under its license and sublicense agreements and other factors that are described in the "Risk Factors" section (Item 1A) of Vanda's annual report on Form 10-K for the year ended December 31, 2007 (File No. 000-51863). In addition to the risks described above and in Item 1A of Vanda's annual report on Form 10-K, other unknown or unpredictable factors also could affect Vanda's results. There can be no assurance that the actual results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved.

All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this release is provided only as of the date of this release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

(*) Lieberman JA, et al. Effectiveness of Antipsychotic Drugs in Patients
with Chronic Schizophrenia. N Engl J Med 2005 Sep 22;353(12):1209-23.

(1) Positive and Negative Symptom Scale Total (PANSS-T)

(2) PANSS Negative (PANSS-N), PANSS Positive (PANSS-P)

(3) Brief Psychiatric Rating Scale (BPRS)

(4) Clinical Global Impression Severity (CGI-S)

(5) Clinical Global Impression of Change (CGI-C)

(6) Barnes Akathisia Scale (BAS)

(7) Extrapyramidal Symptom Ratings Scale (ESRS)

SOURCE Vanda Pharmaceuticals Inc.
Copyright©2008 PR Newswire.
All rights reserved

Related medicine technology :

1. Treprostinil Data to be Presented at Annual Meeting of the American Thoracic Society
2. New Data on SEROQUEL XR(TM) in Treatment of Both Major Depressive Disorder and Generalized Anxiety Disorder Presented at APA Annual Meeting
3. Phase 3 Data Regarding Anti-RSV Antibody To Be Presented at Pediatric Academic Societies (PAS) Annual Meeting
4. Interim Results from Boceprevir Phase II Study in Genotype 1 Treatment-Naive Hepatitis C Patients Presented At EASL
5. Final Results of Ideal Study Presented at Annual Meeting of the European Association for the Study of the Liver (EASL)
6. Data Presented at AAN Support Potential for Adjunctive use of Intravenous Lacosamide as Short-Term Replacement for Oral Treatment in Partial Epilepsy
7. Data Presented at the American Academy of Neurology Show XP13512/GSK1838262 Significantly Improved Symptoms of Moderate-to-Severe Primary Restless Legs Syndrome
8. Data Presented at AAN Show That Lacosamide Significantly Reduced Pain and was Generally Well Tolerated in Patients With Diabetic Neuropathic Pain
9. Preclinical Study Presented at AACR Annual Meeting Shows Peregrines Anti-PS Immunocytokines Can Generate Protective Immune Responses in a Highly Aggressive Breast Cancer Model
10. Data Presented at AACR Annual Meeting Shows Bavituximab Equivalent Plus Docetaxel Reduces Tumor Growth By Up to 95% and Halts Metastasis in a Model of Hormone-Refractory Prostate Cancer
11. Preclinical Study Presented at AACR Annual Meeting Shows Broad Anti-Cancer Potential of Peregrines anti-PS Vascular Targeting Antibodies
Post Your Comments:
(Date:10/11/2017)... , Oct. 11, 2017  Caris Life Sciences ... on fulfilling the promise of precision medicine, today announced ... joined Caris, Precision Oncology Alliance™ (POA) as its 17 ... centers, the St. Jude Crosson Cancer Institute will help ... the use of tumor profiling, making cancer treatment more ...
(Date:10/11/2017)...  Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), today provided ... Piedras, Puerto Rico , where the ... Following a comprehensive onsite ... structural damage, temporary loss of power and minimal water ... manufacturing operations have resumed, and the company expects to ...
(Date:10/10/2017)... , Oct. 10, 2017   West Pharmaceutical Services, ... solutions for injectable drug administration, today shared the results ... Adapter for improving the intradermal administration of polio vaccines. ... Vaccination Summit in May 2017 by Dr. Ondrej ... Department, World Health Organization (WHO), and recently published in ...
Breaking Medicine Technology:
(Date:10/13/2017)... ... October 13, 2017 , ... Southern ... and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice Frueh, ... cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU School ...
(Date:10/13/2017)... ... ... Apple Rehab Shelton Lakes , which specializes in the delivery of sub-acute ... of a disaster drill on October 3rd. , Apple Rehab participated with the Shelton ... well as the Connecticut Long Term Care Mutual Aid Plan (LTC-MAP). The LTC-MAP ...
(Date:10/13/2017)... N.J. (PRWEB) , ... October 13, 2017 , ... The ... Holly Day Market. Featuring a collection of specialty vendors and unique items from across ... personalized and quality-focused health and wellness services offered by the VNA. The boutique ...
(Date:10/13/2017)... NJ (PRWEB) , ... October 13, 2017 , ... Global ... at scenic Alexandria Park in Milford, NJ. This free event, sponsored by Global ... physical activity. The fun run is geared towards children of all ages; it ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented host, actor Rob Lowe, ... in a new episode of "Success Files," which is an award-winning educational program ... investigates each subject in-depth with passion and integrity. , Sciatica occurs when the ...
Breaking Medicine News(10 mins):