Schizophrenia is a chronic, disabling brain disorder which ranks among the top 10 causes of disability in developed countries affecting approximately 1.1% of the population. The schizophrenia market is currently dominated by second generation (atypical) antipsychotics. These products have been very successful in eliminating or reducing the disease symptoms. However, treatment success during the maintenance phase is limited due to poor patient compliance. Furthermore, many atypicals still exhibit extrapyramidal symptoms (EPS) at high plasma levels.
Lack of Medication Adherence
Lack of patient compliance is one of the most frequently cited unmet needs in the treatment of schizophrenia. Patient compliance is estimated at only 40% – 70% of patients. Noncompliance is a major reason that neuroleptic drugs are not more effective in keeping people with schizophrenia out of the hospital and accounts for about 40% of all relapse. If medication is discontinued, the relapse rate is about 80% within 2 years (compared to 40% with continued drug treatment). With each successive relapse, the patient’s long-term prognosis deteriorates and previous level of functioning is rarely achieved.
The cost of Medication Non-Adherence
In addition to the impact of non-adherence to patients, one should also consider the impact on the healthcare system and society overall. Hospital costs from maintenance phase relapse in the United States due to medication noncompliance (i.e., excluding refractory patients) was estimated at over $700 Million per year in 1995. Furthermore, direct healthcare costs are not the only costs associated with relapse. The remaining costs include lost time from work, social services, criminal justice resources, etc. The overall U.S. 2002 cost of schizophrenia was estimated to be $62.7 billion, with $22.7 billion excess direct health care cost. Direct healthcare costs are estimated to be approximately 30% of the total schizophrenia cost, making the total cost of non-adherence over $2.3 Billion per year. Of course the largest intangible cost is suffered by the patients and their families.
The Impact of Long Acting Formulations
Depot formulations have been introduced in the schizophrenia market and have illustrated the positive impact of long acting formulations in improving clinical outcomes. In 2003 the first atypical depot, Risperdal® Consta® (Consta), was introduced to the market. Consta, which is a 2 week injectable formulation of risperidone, showed very quickly the pharmacoeconomic benefits of a longer acting formulation by improving patient adherence. Two new atypical depot products have also been approved by the FDA last year.
The Limitations of Depot Formulations
Although depot formulations have demonstrated significant benefits, they display certain limitations including:
- Technical limit of depot technologies to provide consistent blood levels for more than 2-4 weeks.
- Safety issues since the drug cannot be withdraw if needed
- Poor pharmacokinetic profile resulting in side effects at high plasma.
The Future of Schizophrenia Treatment
The schizophrenia pipeline is weak and all six blockbuster atypical antipsychotics have lost (or will soon lose) exclusivity. Developing longer acting formulations and overcoming the limitations of depot technologies is the way to improve clinical outcomes and provide key differentiation in this important market. Delpor is currently developing two products (DLP-114 and DLP-115) which will offer the following treatment benefits:
- 3-6 month system offering improved adherence to the medication
- Ability to withdraw the medication if needed (not possible with the current formulations)
- Superior pharmacokinetic profile (no peaks and troughs resulting in safety and efficacy)
- Reduced invasiveness compared to depot formulations (one procedure several painful injections)
- Reduced cost (fewer relapses and doctor visits)