It is an exciting time within the schizophrenia market as numerous monotherapies and adjunctive therapies are being developed to address some of the most important unmet needs observed with current antipsychotic treatments, says GlobalData. Key opinion leaders (KOLs) interviewed by the leading data and analytics company were hopeful that these novel pipeline agents might help provide more complete symptom relief to a larger patient population.

The current schizophrenia treatment landscape includes many established atypical antipsychotic products that can help manage the positive symptoms of the disorder, such as hallucinations, delusions, and disorganized speech. However, these are only effective in a portion of patients.

Christie Wong, Pharma Analyst at GlobalData, comments: “At the moment, all the atypical antipsychotic drugs used for schizophrenia target similar signalling pathways and therefore have a similar efficacy profile in reducing the severity of psychotic thoughts and behaviors. They are differentiated only by slight differences in their safety profiles. Unfortunately, these atypical antipsychotic drugs are not effective in all patients.”

A recent survey* by GlobalData has revealed that treatment options for cognitive impairment, treatment-resistant disease, and the negative symptoms of schizophrenia were consistently ranked by high-prescribing psychiatrists as the most significant unmet needs in the schizophrenia market (ranking from 1 to 9, where 1 indicated the most significant need and 9 the least significant). This trend was mirrored throughout the 7MM**.

Wong continues: “KOLs interviewed by GlobalData indicated that 30% of patients have only a partial response to antipsychotics, with residual symptoms remaining even after treatment. Another 30% of patients are treatment-resistant and fail to respond to at least two different antipsychotic drugs, including an atypical antipsychotic.

“Clozapine, a drug associated with severe neurological and metabolic side effects, is the only approved drug available for these treatment-resistant patients. If patients do not respond to clozapine treatment, it leaves psychiatrists with no further treatment options to administer to their patients.”

Both negative symptoms and impairments in cognition are common in schizophrenia patients and contribute significantly to the disability of the disease. Impairments in cognitive functioning include aspects of attention, concentration, memory, reasoning, and processing speed. Negative symptoms of schizophrenia refer to symptoms like lack of motivation, social withdrawal, and flat emotional affect.

Wong notes: “Negative symptoms and cognitive impairment greatly impact the ability of people with schizophrenia to live the lives they want to. KOLs interviewed by GlobalData agreed that these untreated symptoms have a major impact on the quality of life of the patient, as these symptoms persist even during periods of positive symptom remission.”

Fortunately, several pipeline drugs with novel mechanisms of action are in development that may help address these unmet needs. For example, Neurocrine Biosciences’ Ingrezza (valbenazine), Karuna Therapeutics’ KarXT (trospium chloride + xanomeline), and Acadia Pharmaceutical’s Nuplazid (pimavanserin tartrate) are adjunctive therapies with novel mechanisms of action that may help manage the positive and negative symptoms in patients who do not respond adequately to standard treatment.

In addition, Boehringer Ingelheim’s BI-425809 and Biogen’s BIIB104 (pesampator) are in development to target the cognitive impairment associated with schizophrenia. Furthermore, Minerva Neurosciences’ roluperidone is under investigation to specifically manage the negative symptoms in adult patients with schizophrenia.

*2022 Schizophrenia high prescriber survey: GlobalData surveyed 84 high-prescribing psychiatrists, who represented the 7MM. The survey was launched in and completed in June 2022.

**7MM: US, France, Germany, Italy, Spain, UK, and Japan.