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Schizophrenia Therapy Options Increasing

Kunj Gohil PharmD, RPh
Brielle Carramusa

Schizophrenia is a complex, chronic psychiatric disorder associated with an array of debilitating symptoms.1 The global prevalence in 2012 was approximately 2.5 million patients, 2 million of whom were receiving treatment. Therapies that year yielded $5.2 billion in U.S. market sales and $6.3 billion in global market sales. By 2022, those figures are expected to grow to $6.1 billion in the U.S. and $7.9 billion globally.2

Schizophrenia symptoms are classified into three categories: positive, negative, and cognitive. Positive manifestations, which include hallucinations and delusions, are the most easily recognizable. Negative symptoms are more psychosocial: for example, emotional flattening and lack of speech. Cognitive dysfunctions consist of impairments in attention, working memory, and executive function.1

First-generation (typical) anti-psychotics, the first drugs approved for the treatment of schizophrenia, were discovered starting more than 50 years ago.3 Although they were effective in treating positive symptoms, they were associated with a high occurrence of extrapyramidal side effects (EPS).3 This led to the development of second-generation (atypical) anti psychotics, which did not carry the risk of EPS and demonstrated a greater clinical benefit in patients.3

Current Food and Drug Administration (FDA)–approved medications for schizophrenia address positive symptoms, but fall short in treating negative and cognitive symptoms.4 Most therapies require daily dosing, which contributes greatly to the poor adherence seen in up to two-thirds of schizophrenic patients.5

Future therapies, which include new long-acting injectables and drugs with novel mechanisms of action to target negative and cognitive symptoms, are in the works to help patients better manage this disease.1

Future Therapies

Drug Manufacturer Status Regimen Information Pivotal Studies Expected Approval Anticipated Peak Year Sales/Pricing
Aripiprazole lauroxil Alkermes Phase 3 IM injection: 300 mg or 600 mg once monthly NCT01469039 2015 Aripiprazole lauroxil will likely enter the market at a 3%–5% markup over Abilify Maintena because it does not require reconstitution
Cariprazine Forest Labs Phase 3 Oral: 3–9 mg once daily NCT01412060
NCT01104792
NCT01104779
NCT01104766
2015 The atypical cariprazine is expected to be priced at a 2%–4% premium over the highest-cost branded oral therapy at the time of its launch
Brexpiprazole Otsuka/Lundbeck Phase 3 Oral: 1–4 mg daily EQUATOR (NCT01668797) NCT01810380 2015 Otsuka is expected to price brexpiprazole (the follow-up drug to aripiprazole) in reference to Abilify, with a 25% markup projected in the U.S. and Japanese markets and a 2%–5% markup in the EU
Zicronapine Lundbeck Phase 3 Oral: 7 mg once daily NCT01295372
NCT00768326
2015 Zicronapine will be priced competitively with Saphris (asenapine); a small (0%–2%) discount may be applied
Bitopertin Roche Phase 3 Oral: once daily NCT01235559
NCT01192880
NCT01235585
NCT01192906
2015 A novel therapy that is intended to fulfill a major unmet need by treating negative symptoms, bitopertin is expected to be priced at an approximate 20% premium over current brands
EVP-6124 Bayer Phase 3 Oral: 0.3–1 mg daily NCT00968851
NCT00968851
NCT01714661
2019 EVP-6124 is expected to be priced 5%–7% higher than bitopertin, as it will introduce a new therapeutic class and target cognitive symptoms, which is a large unmet need in the atypicals market

EU = European Union; IM = intramuscular

Sources: GlobalData; ClinicalTrials.gov; manufacturers’ websites: Alkermes, Forest, Otsuka, Lundbeck, Roche, Bayer; FierceBiotech

Current Therapies

Drug Manufacturer Approval Date Indicationa Regimen Informationb Approximate Cost of Course of Therapy Per Year c
First-Generation (Typical) Antipsychotics (5 most recent FDA-approved drugs with schizophrenia/psychosis indications)
Loxapine February 25, 1975 Adult SCZ 20–60 mg daily $476–$1,427d
Thiothixene July 24, 1967 Adult and adolescent SCZ Moderate: 15 mg daily
Severe: 20–30 mg daily
Moderate: $303e
Severe: $259–$388d
Haloperidol April 12, 1967 Adult and child psychosis 1–15 mg daily; also available as LAI $150f–$897e
Thioridazine March 15, 1962 Adult, adolescent, and child SCZ and psychosis 200–800 mg daily $498–$1,992g
Fluphenazine December 23, 1959 Adult psychosis 1–5 mg daily; also available as LAI $46–$231f
Second-Generation (Atypical) Antipsychotics
Latuda (lurasidone hydrochloride) Sunovion Pharmaceuticals October 28, 2010 Adult SCZ; depressive episodes seen in adult BP1 40–160 mg per day $8,519–$34,076h
Saphris (asenapine maleate) Forest Pharmaceuticals August 13, 2009 Adult SCZ; manic or mixed episodes associated with adult BP1 10–20 mg daily $4,195–$8,391d
Fanapt (iloperidone) Novartis May 6, 2009 Adult SCZ 12–24 mg daily $4,659–$9,318i
Invega (paliperidone) Janssen December 19, 2006 Adult and adolescent SCZ; adult SZA 3–12 mg daily; also available as LAI $8,876–$35,505j
Abilify (aripiprazole) Otsuka/Lundbeck November 15, 2002 Adult and adolescent SCZ; adult and child BP1; adult MDD; irritability with adolescent autism 10–15 mg daily; also available as LAI $18,889–$28,333e
Geodon (ziprasidone hydrochloride) Pfizer February 5, 2001 Adult SCZ; manic or mixed episodes associated with adult BP1; adult BP1 40–160 mg daily $4,276–$17,105h
Seroquel (quetiapine) AstraZeneca September 26, 1997 Adult and adolescent SCZ; adult, adolescent, and child BP1 400–800 mg daily $7,074–$14,148k
Zyprexa (olanzapine) Eli Lilly September 30, 1996 Adult, adolescent, and child SCZ; adult and adolescent mania seen in BP1 10–20 mg daily; also available as LAI $6,731–$13,461d
Risperdal (risperidone) Janssen December 29, 1993 Adult and adolescent SCZ; adult, adolescent and child BP1; irritability with adolescent and child autism 4–8 mg daily; also available as LAI $7,196–$14,391l
Clozaril (clozapine) Novartis September 26, 1989 SCZ; suicidal behavior in adult SCZ and SZA 300–450 mg daily $11,921 g–$18,962m

BP1 = bipolar I disorder; MDD = major depressive disorder; LAI = long-acting injectable; SZA = schizoaffective disorder; SCZ = schizophrenia

aAbbreviated indication for oral formulation provided; for full indication, please refer to prescribing information

bRegimens based on the recommended dosage and maintenance phases from prescribing information

cCosts calculated for oral regimens, using wholesale acquisition cost (WAC) and rounded to the nearest dollar

dCost calculated using 10 mg WAC price and regimen provided

eCost calculated using 5 mg WAC price and regimen provided

fCost calculated using 1 mg WAC price and regimen provided

gCost calculated using 100 mg WAC price and regimen provided

hCost calculated using 40 mg WAC price and regimen provided

iCost calculated using 12 mg WAC price and regimen provided

jCost calculated using 3 mg WAC price and regimen provided

kCost calculated using 400 mg WAC price and regimen provided

lCost calculated using 4 mg WAC price and regimen provided

mCost calculated using 100 mg and 25 mg WAC prices and regimen provided

Sources: GlobalData, Redbook, Drugs@FDA, prescribing information for each medication

References

  1. Crismon L, Argo TR, Buckley PF. Schizophrenia In: DiPiro JT, Talbert RL, Yee GC. Pharmacotherapy: A Pathophysiologic Approach. 9th edNew York: McGraw-Hill. 2014;1019–1046.
  2. Global Data. Schizophrenia—Global Drug Forecast and Market Analysis to 2022 February 2014;
  3. Gray JA, Roth BL. The pipeline and future of drug development in schizophrenia. Mol Psychiatry 2007;12;(10):904–922.
  4. Citrome L. Unmet needs in the treatment of schizophrenia: new targets to help different symptom domains. J Clin Psychiatry 2014;75;(suppl 1):21–26.
  5. Kaplan G, Casoy J, Zummo J. Impact of long-acting injectable antipsychotics on medication adherence and clinical, functional, and economic outcomes of schizophrenia. Patient Prefer Adherence 2013;7:1171–1180.