Invega

Product
Invega

Approval Date
December 19, 2006
 
Release Date
January 31, 2007
 
Company
Janssen

Class
Antipsychotic (benzisoxazole)
 
Active Ingredient
Paliperidone 3mg, 6mg, 9mg; ext-rel tabs.
 
Indication
Schizophrenia
 
Agency Roster
Blue Diesel
Cline Davis & Mann LLC
The Falk Group, LLC

Marketing Strategy/Execution
Janssen’s once-daily, oral atypical antipsychotic is the successor to Risperdal, which generated $2.5 billion in US sales in 2006. Early results show the pill is off to a slow start: US sales were $75 million through the first seven months of 2007, according to IMS Health, due in part to a warning on Invega’s label of a potentially fatal heart side effect. A bipolar mania filing is expected in 2008 that would add to its schizophrenia label. Risperdal’s label already supports both indications. J&J has said Invega is tracking with expectations but that MCOs have been restrictive in the use of the drug based on formulary status. J&J filed an NDA for a once-monthly injectable form of Invega.
 
The Market

Physician Outlook
Our early physician research shows Invega is perceived as less efficacious but better tolerated relative to its parent drug, Risperdal. Invega’s success will be challenged on two fronts: Risperdal’s loss of patent exclusivity in the first half of 2008 and psychiatrists’ reliance and need for more “powerful” efficacy in the schizophrenia marketplace.
 
—Geoff Penney, VP, category business leader, Psychiatry, GfK Market Measures, October 2007
 
Also in the Pipeline (courtesy of Adis R&D Insight)
Drug: Abilitat
Manufacturer: Otsuka Pharmaceutical/Bristol-Myers Squibb
Active ingredient: Aripiprazole
Indication: Depression, ADHD, autism, psychotic disorders, Asperger syndrome, cognition disorders, drug abuse
Phase: Filed, III (ADHD, autism, psychotic disorders), II (Asperger syndrome), Preclinical (cognition disorders, drug abuse)
 
Drug: Zyprexa
Manufacturer: Eli Lilly
Indication: Bipolar disorders, Schizophrenia, Personality disorders, Gilles de la Tourette’s syndrome
Active ingredient: Olanzapine
Phase: Filed, III (Personality Disorders), Clinical (Gilles de la Tourette’s syndrome)
 
Drug: INVEGA/ RO 76477/RO 92670
Manufacturer: Johnson & Johnson
Indication: Bipolar disorders, Manic episodes, Schizoaffective disorder, Schizophrenia
Active Ingredient: Paliperidone/9-hydroxyrisperidone
Phase: III
 
Drug: CP 88059/ Geodon/ Zeldox
Manufacturer: Pfizer
Indication: Bipolar disorders, Schizophrenia, Bipolar depression, Bipolar disorders, Anxiety disorders
Active Ingredient: Ziprasidone mesylate
Phase: Approved (Bipolar disorders, Schizophrenia), III (Bipolar depression, Bipolar disorders), Preclinical (Anxiety Disorders)
 
Drug: DU 127090
Manufacturer: Lundbeck A/S, Wyeth
Indication: Schizophrenia, Bipolar disorders
Active Ingredient: Bifeprunox
Phase: Filed (Schizophrenia), III (Bipolar disorders)
 
Drug: Zomaril
Manufacturer: Sanofi-Aventis
Indication: Schizophrenia
Active Ingredient: Iloperidone
Phase: Filed
 
Drug: ORG 5222
Manufacturer: Organon
Active Ingredient: Asenapine
Indication: Bipolar disorders, Psychotic disorders, Schizophrenia
Phase: III
Source: Wolters Kluwer Health, Oct. 2007
 
Recent MM&M Coverage
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Medical/Surgical Journal Ad Review
‘Fully Engaged’ docs more open to influence
Specialties Journal Ad Review: Feeling the Pinch
Heavyweights Fall Hard
Mixed Fortunes
Tough Losses
Move over lithium; FDA sanctions use of Risperdal in teens
Product News from the 05/01/07 News Brief
Risperdal changeover tests J&J
Product News from the 01/02/07 News Brief
Janssen to launch Risperdal offshoot next month
 
Pharmacology
Paliperidone is the major active metabolite of risperidone. Although the mechanism of action of this atypical antipsychotic is unknown, the therapeutic effect may be due to a combination of central dopamine Type 2 (D₂) and serotonin Type 2 (5HT_2a) receptor antagonism. Paliperidone also antagonizes at a₁ and a₂ adrenergic receptors and H1 histaminergic receptors.
Invega tablets use osmotic pressure to deliver paliperidone at a controlled rate. Peak plasma concentrations occur approximately 24 hrs after dosing; steady state concentrations are attained within 4–5 days.
Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is coadministered with paliperidone.
 
Clinical Trials
The short-term efficacy of paliperidone was determined in three placebo-controlled and active-controlled (olanzapine), 6-week, fixed-dose trials involving 1665 patients who met DSM-IV criteria for schizophrenia. The doses studied among these three trials included 3, 6, 9, 12, and 15mg/day. Efficacy was evaluated using the Positive and Negative Syndrome scale (PANSS) and the Personal and Social Performance scale (PSP). In all three studies, paliperidone was superior to placebo on the PANSS at all doses. Paliperidone was also superior to placebo on the PSP in these trials.
The efficacy of paliperidone has not been evaluated in placebo-controlled trials for longer than six weeks. Therefore, patients who are taking paliperidone for extended periods should be reevaluated periodically.
 
Adverse Reactions
Tachycardia, extrapyramidal effects, akathisia, dizziness, anxiety, somnolence, headache, GI upset; may cause neuroleptic malignant syndrome, tardive dyskinesia, QT prolongation, hyperglycemia, orthostatic hypotension, syncope, hyperprolactinemia, priapism.
 
Adults
Swallow whole. =18yrs: 6mg once daily in AM; may increase in increments of 3mg/day at intervals of >5 days if needed. Max 12mg/day. Renal impairment: CrCl =50–80mL/min: max 6mg/day; CrCl 10–< 50mL/min: max 3mg/day.
 
Children
<18yrs: not recommended.
 
Precautions
Avoid in congenital long QT syndrome, cardiac arrhythmias. Diabetes risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia. Pre-existing severe GI narrowing: not recommended. Cardio- or cerebrovascular disease. Orthostatic hypotension. History of seizures. Patients at risk for aspiration pneumonia. Renal insufficiency. Severe hepatic impairment. Exposure to extreme temperatures. May have antiemetic effect. Suicidal patients. Reevaluate periodically. Elderly (not for dementia-related psychosis); consider monitoring renal function and for orthostatic effects. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions
Avoid alcohol, drugs that prolong QT interval (eg, Class 1A and Class III antiarrhythmics). Caution with other CNS drugs. May antagonize levodopa, other dopamine agonists.