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Iloperidone Results Show Favorable Akathisia Profile

September 12, 2017

According to study results presented today at the 2007 American Psychiatric Association annual meeting, iloperidone, an investigational atypical antipsychotic, was shown to have a favorable akathisia profile. Akathisia a debilitating sensation of restlessness that manifests as an inability to sit still is a frequent side effect of antipsychotic medications. Iloperidone is being studied by Vanda Pharmaceuticals Inc. (NASDAQ: VNDA), a biopharmaceutical company working to advance the science of personalized medicine.

"Many people who have akathisia will say that it is the worst experience in their life, and at its worst it can even lead to suicidal behavior given its severity. It is not a surprise that akathisia can lead to medication discontinuation, leading to further symptoms and relapse," said Peter Weiden, M.D., Director of the Psychosis Program of the Department of Psychiatry at the University of Illinois at Chicago. "Many of the newer medications have less akathisia than older antipsychotics, but it is still a significant problem. These findings suggest that iloperidone has a very low akathisia profile, which is positive news for patients with schizophrenia, and the physician community."

Akathisia was assessed in a Phase III trial conducted by Novartis, in which 706 patients were studied over six weeks at two dose ranges of iloperidone (12-16 mg/d, 20-24 mg/d) with placebo and risperidone controls (6-8 mg/d). When akathisia was measured on the Barnes Akathisia Scale (BAS), the iloperidone groups had fewer patients whose total akathisia score worsened (12%, p=0.04; 8%, p=0.004), compared to placebo (20%). The risperidone group (20%, p=1.00) was equal to placebo.

Three times as many patients in the risperidone group (22%), compared to placebo (7%), received anticholinergic medication to manage intolerable extrapyramidal symptoms (EPS) (such as tremor, slurred speech, restlessness and involuntary muscle movement) during the course of the study. In contrast, 5% of low-dose and 11% of high-dose iloperidone patients received anticholinergic medication.

"Iloperidone may be less likely to worsen akathisia because of its novel mechanism of action," said Paolo Baroldi, M.D., Ph.D., Chief Medical Officer, Vanda Pharmaceuticals Inc. "Akathisia is believed to be due to D2 activation, which is not present with iloperidone."

About the Study

In this Phase III randomized, double-blind, placebo- and risperidone-controlled, international multi-center six-week study conducted by Novartis, patients were randomized to one of four treatment groups: iloperidone low-dose (12�'16 mg/d, n=244), iloperidone high-dose (20�'24 mg/d, n=145), risperidone (6�'8 mg/d, n=157) or placebo (n=160).

Patients enrolled in the study were 62% male (n=435) and 38% female (n=271), approximately 39 years of age, and had a diagnosis of schizophrenia or schizoaffective disorder with a Positive and Negative Syndrome Scale (PANSS) score ≥60 at baseline.

Anticholinergic drugs for the treatment of EPS were permitted during the two-day placebo run-in period. EPS must have improved and anticholinergics discontinued for more than 24 hours prior to baseline measurement.

Changes in akathisia were measured weekly by the BAS and the Extrapyramidal Symptom Rating Scale (ESRS) from baseline to the six-week end point for patients in all treatment groups. Categorical analysis was conducted to determine the percentage of patients with akathisia that worsened, remained unchanged, or improved, from baseline, during the treatment period. Use of anticholinergics (benztropine or biperiden) was allowed during the double-blind phase in all four groups for treatment-emergent EPS, after assessment was completed by the EPS rating scales.

About Iloperidone

Iloperidone is an atypical antipsychotic, with a dual serotonin and dopamine receptor antagonist profile. Clinical trial experience with iloperidone suggests that this balanced antagonism may provide efficacy against positive and negative symptoms of schizophrenia, while causing reduced EPS and hyperprolactinemia relative to other available atypical antipsychotics. Iloperidone also appears to have a favorable weight and metabolic profile. In addition, Vanda is developing a genetic blood test to help identify those patients most likely to benefit from iloperidone.

Vanda has completed its Phase III program for iloperidone in schizophrenia and expects to file a new drug application (NDA) for the oral formulation in Q4 2007. Vanda is also developing a four-week injectable formulation of the compound.

About Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder that affects approximately one percent of Americans. Patients suffering from schizophrenia exhibit a range of symptoms, which are classified into three broad categories:

-- Positive symptoms reflect an excess or distortion of normal functions (e.g., hallucinations, delusions, thought and movement disorders).

-- Negative symptoms represent a loss or decrease in the ability to initiate plans, speak, express emotion, or find pleasure in everyday life.

-- Cognitive symptoms include problems with attention, memory or planning, and often interfere with normal routines.

Unmet Needs in Schizophrenia

Although there are many drugs approved to treat schizophrenia, including the commonly prescribed "atypical antipsychotics," a high degree of dissatisfaction remains among physicians and patients. The recent CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, conducted by the National Institute of Mental Health and reported in The New England Journal of Medicine, evaluated several antipsychotic medications and revealed that 74% of patients taking antipsychotics discontinued treatment within 18 months, primarily because of insufficient efficacy and tolerability issues.

About Vanda Pharmaceuticals Inc.

Vanda Pharmaceuticals Inc., headquartered in Rockville, Maryland, is a biopharmaceutical company working to advance the science of personalized medicine to improve the lives of patients with schizophrenia. The company has three product candidates in clinical development. Vanda's lead product candidate, iloperidone, is a compound for the treatment of schizophrenia and has completed its Phase III program. Vanda's second product candidate, VEC-162, is a compound for the treatment of sleep and mood disorders which is currently in Phase III for insomnia. Vanda's third product candidate, VSF-173, is a compound for the treatment of excessive sleepiness and is ready for a Phase II clinical trial. For more on Vanda Pharmaceuticals Inc., please visit vandapharma.

Note Regarding Forward-Looking Statements

This release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Words such as, but not limited to, "suggest," "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "plan," "targets," "likely," "will," "may," "would," "should," and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, a failure of iloperidone or Vanda's other product candidates to be demonstrably safe and effective, a failure to obtain regulatory approval for iloperidone or the company's other product candidates, a lack of acceptance of iloperidone or Vanda's other product candidates in the marketplace, a failure of the company to become or remain profitable, Vanda's inability to obtain the capital necessary to fund its research and development activities, a loss of any of the company's key scientists or management personnel, 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, 2006 (File No. 000-51863). No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Vanda undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

Vanda Pharmaceuticals Inc.