Product
Fanapt
Approval Date
May 6, 2009
Release Date
January 11, 2010
Company
Novartis/Vanda Pharmaceuticals
Class
Antipsychotic (piperidinyl-benzisoxazole atypical)
Indication
Acute treatment of schizophrenia in adults.
Active Ingredient
Iloperidone
Agency Roster
The Cement Bloc, Inc. (professional)
Marketing Strategy/Execution
Novartis’ brand-new psychiatry field force began detailing Fanapt to specialists in January 2010, a mere two months following completion of its North American marketing deal with developer Vanda. However, the reps were armed only with package inserts because the advertising materials had not been approved by DDMAC yet. Without the usual glossy sales aids to enhance their educational efforts, reps began stressing Fanapt’s proven tolerability profile. In clinical trials, the incidence of akathisia, a feeling of inner restlessness often associated with other antipsychotics, was comparable between Fanapt and placebo, as was the discontinuation rate. Fanapt was not associated with medically important changes in triglyceride or total cholesterol measurements, and the atypical antipsychotic showed a low incidence of parkinsonism, dystonia, dyskinesia and bradykinesia. Notwithstanding Fanapt’s better tolerability, psychiatrists may be more likely to prescribe Eli Lilly’s Zyprexa (olanzapine) or AstraZeneca’s Seroquel (quetiapine), two very popular antipsychotics set to go generic in 2011. Long-acting formulations of atypicals, namely Janssen’s Invega Sustenna (paliperidone), could provide competition, too. While a four-week injectable “depot” formulation of Fanapt is being developed by Novartis to complement the existing twice-a-day oral version, there remains a good deal of uncertainty around the ability of Vanda and Novartis to expand the antipsychotic market.
Physician Outlook
Physicians will struggle to find the unique aspects of Fanapt that will encourage trial. Fanapt meets the positive and negative symptom efficacy requirements. As well, this newest atypical anti-psychotic offers a comparable side effect profile (including lower incidence of weight gain). The challenge for Novartis is that other more established products have been associated with these benefits for some time.
– Geoff Penney, Ph.D., Vice President, Research, GfK Healthcare
Also in the Pipeline (courtesy of Adis R&D Insight)
Drug: Abilify
Manufacturer: Bristol-Myers Squibb
Indication: Bipolar disorders (children), Psychotic disorders
Active ingredient: Aripiprazole
Phase: Phase III
Drug: Staccato/ALXZ-004
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Indication: Bipolar disorders, Schizophrenia
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Drug: Lurasidone/SM 13496
Manufacturer: Dainippon Sumitomo Pharma
Indication: Bipolar disorders, Schizophrenia
Active ingredient: Lurasidone
Phase: Phase III (bipolar disorders), Preregistration (schizophrenia)
Drug: Invega
Manufacturer: Johnson & Johnson
Indication: Aggression, Bipolar disorders, Manic episodes, Schizophrenia (in adolescents)
Active ingredient: Paliperidone
Phase: Phase III
Drug: S 1991
Manufacturer: Lundbeck A/S
Indication: Schizophrenia
Active ingredient: Sertindole
Phase: Preregistration
Drug: Saphris
Manufacturer: Organon
Indication: Psychotic disorders
Active Ingredient: Asenapine
Phase: Phase III
Drug: Zyprexa
Manufacturer: Eli Lilly
Indication: Personality disorders
Active Ingredient: Olanzapine
Phase: Phase III
Source: Wolters Kluwer Pharma Solutions
Recent MM&M Coverage
Professional Marketing: Novartis, Epocrates, Cegedim Dendrite and SK&A Information Services
Pharmacology
Iloperidone is an atypical antipsychotic agent whose efficacy in the treatment of schizophrenia may be due to its antagonism at dopamine types 2 and 3 (D2, D3) and serotonin type 2A (5-HT2A) receptors in the CNS.
Clinical Trials
Two placebo- and active-controlled clinical trials were conducted to assess the efficacy of iloperidone in the treatment of schizophrenia. A 6-week trial compared two doses ranges for iloperidone (12–16mg/day and 20–24mg/day, after titration) to placebo and an active control drug. The primary endpoint was the change from baseline on the Brief Psychiatric Rating Scale (BPRS) total score at the end of treatment (day 42). Both dose ranges for iloperidone were superior to placebo. Within the first 2 weeks, the active control psychiatric drug appeared to be superior to iloperidone. This may be explained by the more rapid titration that was possible for that drug.
In a 4-week trial, iloperidone 24mg/day after titration was compared to placebo and an active control drug which also required an initial titration phase. The primary efficacy endpoint was the change in baseline on the Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment (day 28). In this study, iloperidone was superior to placebo and had similar efficacy to the active control medication.
Adverse Reactions
Dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, increased weight; QT prolongation (discontinue if QTc >500msec persists), priapism, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, dysphagia.
Adults
≥18yrs: 1mg twice daily on day 1, 2mg twice daily on day 2, 4mg twice daily on day 3, 6mg twice daily on day 4, 8mg twice daily on day 5, 10mg twice daily on day 6, 12mg twice daily on day 7; target range 6–12mg twice daily; max 24mg/day. Reduce dose by 1/2 with concomitant strong inhibitors of CYP2D6 or CYP3A4. Retitrate if therapy suspended >3 days. Reassess periodically.
Children
<18yrs: not recommended.
Precautions
Bradycardia, hypokalemia, hypomagnesemia, congenital QT prolongation, recent MI, uncompensated heart failure, arrhythmias: avoid (risk of torsades de pointes/sudden death). Cardio- or cerebrovascular disease. Monitor electrolytes esp. K+, Mg++. Hepatic impairment: not recommended. Diabetes or risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia. History of breast cancer or seizures. Orthostatic hypotension. Pre-existing low WBC count or history of leukopenia/neutropenia: monitor CBC during 1st few months of therapy; discontinue if WBCs decline. Exposure to extreme heat. Dehydration. Suicidal tendencies. Write Rx for the smallest practical amount. Monitor for neuroleptic malignant syndrome. Elderly (not for dementia-related psychosis). Pregnancy (Cat.C). Nursing mothers: not recommended.
Interactions
Avoid other drugs that cause QT prolongation (eg, quinidine, amiodarone, sotalol, procainamide, chlorpromazine, thioridazine, moxifloxacin, methadone). May potentiate antihypertensives. Caution with alcohol, CNS depressants. Potentiated by inhibitors of CYP2D6 (eg, fluoxetine, paroxetine) or CYP3A4 (eg, clarithromycin, ketoconazole).
