Introduction:What Clinical Attributes Will Be Most Persuasive for Psychiatrists and Payers Regarding the First Novel Drugs in this Highly Underserved Arena?
Decision Resources Group forecasts the number of diagnosed prevalent cases of schizophrenia with comorbid cognitive impairment to exceed 4 million in the seven major pharmaceutical markets in 2022. Cognitive impairment associated with schizophrenia (CIAS)—which may include deficits in attention, working memory, and executive function—has a negative impact on patients’ quality of life and ability to function. Although cognitive symptoms in schizophrenia are well characterized, no formal diagnostic criteria exist. Furthermore, no pharmacological agents are approved to treat the condition, and no marketed therapy tested to date has established clear, meaningful efficacy, which underscores the difficulty of drug development in this arena and accentuates the unmet need for proven treatment options. Significant commercial opportunity awaits future innovative therapies that can improve cognition and functional capacity in schizophrenia patients as adjunctive therapy to antipsychotic medication.
Questions Answered in This Report:
A drug’s performance on at least eight efficacy end points, including effect on patient function, is important for drug approval and physician use in CIAS. What are the key primary and secondary clinical trial end points with which new CIAS therapies are evaluated? How do U.S. and European psychiatrists weight efficacy measures and other drug attributes in their prescribing decisions for CIAS?
CIAS agents offering an improved effect on patient function and a lower risk of psychiatric side effects are key areas of unmet need according to the insights of surveyed U.S. and European psychiatrists. Are therapies in development for CIAS poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new CIAS therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?
A novel CIAS drug’s effect on positive and negative symptoms and effect on patient function as adjunctive therapy to antipsychotic medication are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new CIAS therapies. What trade-offs across these and other clinical attributes are U.S. psychiatrists willing to make when considering the use of emerging therapies for the treatment of CIAS? Based on the trade-offs in price and performance across key drug attributes that U.S. psychiatrists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for CIAS?
EnVivo Pharmaceuticals/Bayer HealthCare/Mitsubishi Tanabe Pharma’s encenicline emerges as the future gold-standard therapy in our Drug Comparator Model because of its potentially superior clinical profile over the key current therapies we evaluated. On what clinical attributes is encenicline most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by encenicline?
Attributes included in conjoint analysis based assessment of target product profiles for CIAS:
- Overall cognition–standard-deviation improvement (effect size) from baseline over placebo on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB).
- Patient function–standard-deviation improvement (effect size) from baseline over placebo on the UCSD Performance-Based Skills Assessment (UPSA).
- Positive and negative symptoms–standard-deviation change (effect size) from baseline over placebo on the Positive and Negative Symptom Scale (PANSS).
- Incidence of serious or life-threatening side effects.
- Incidence of nausea.
- Dosing frequency.
- Price per day.
Attributes included in assessment of U.S. payers’ receptivity to new therapies for CIAS:
- Improvement in overall cognition provided by a new CIAS drug prescribed as adjunctive therapy to an antipsychotic regimen.
- Improvement in patient function provided by a new CIAS drug prescribed as adjunctive therapy to an antipsychotic regimen.
- Improvement in positive and negative symptoms provided by a new CIAS drug prescribed as adjunctive therapy to an antipsychotic regimen.
- Incidence of nausea associated with use of a new, effective CIAS drug prescribed as adjunctive therapy to an antipsychotic regimen.
Physicians surveyed: 60 U.S. and 31 European psychiatrists.
Payers surveyed: 20 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- Donepezil (Pfizer/Eisai’s Aricept, other brands, generics)
- Modafinil (Teva’s Provigil, generics)
- Armodafinil (Teva’s Nuvigil)
- Memantine (Merz Pharmaceuticals/Grünenthal’s Axura; Lundbeck’s Ebixa, generics; Forest Laboratories’ Namenda/Namenda XR; Daiichi Sankyo’s Memary)
Rivastigmine (Novartis’s Exelon/Exelon Patch, other brands, generics)
- EnVivo Pharmaceuticals/Bayer HealthCare/Mitsubishi Tanabe Pharma’s encenicline
- AbbVie’s ABT-126
- Omeros’s OMS-824
- Avineuro’s AVN-211
- Teva’s irdabisant