Karuna Therapeutics recently announced positive topline results from the Phase III EMERGENT-2 trial of KarXT (xanomeline + trospium chloride) in acutely psychotic hospitalized adult patients with schizophrenia. According to GlobalData, if KarXT continues to show success within the EMERGENT trial program as a monotherapy, as well as in the ongoing ARISE trial as an adjunctive to traditional antipsychotics, the drug could have a major competitive edge over current atypical antipsychotics, particularly pricey, later-generation products.

The leading data and analytics company notes that Karuna Therapeutics will need to replicate its findings in its three ongoing EMERGENT trials in order to confirm that the drug can improve both positive and negative symptoms of schizophrenia, while not being associated with common side-effects of antipsychotics including weight gain, sedation, and movement disorders.

Christie Wong, Pharma Analyst at GlobalData, comments: “Unlike the atypical antipsychotics, KarXT does not modulate dopamine or serotonin signalling in the brain, instead targeting muscarinic acetylcholine receptors. This product could potentially offer a novel mechanism of action to the schizophrenia market, something not seen for many years.”

However, as numerous atypical antipsychotics and their generics dominate the schizophrenia market, it is unlikely that KarXT monotherapy will be used as a first-line treatment option. Key opinion leaders (KOLs) interviewed by GlobalData worried that patient uptake of novel monotherapies, such as KarXT, was likely to be limited by premium prices, compared to current antipsychotic treatments, such as generic aripiprazole and risperidone, and thus restricted reimbursement by payers.

Wong adds: “In an effort to expand the potential for patient uptake, Karuna is also positioning KarXT as an adjunctive therapy for the treatment of schizophrenia, targeting patients who have a partial response to antipsychotic medication. As such, KarXT can be used in combination with the marketed antipsychotics, rather than having to compete with them, which could greatly help Karuna establish itself within the crowded schizophrenia market.”

At present, although physicians will occasionally prescribe a second antipsychotic or antidepressant off-label to augment the effects of an antipsychotic, there are no approved combination therapeutic regimens for schizophrenia. Furthermore, KOLs reported only modest improvements in efficacy and increased side-effect burden with this type of polypharmacy.

Wong notes: “KOLs were hopeful that KarXT as an adjunctive therapy could benefit patients who have a partial response to current antipsychotic medication, a group that accounts for about 30% of total drug-treated cases. If positive results are achieved in Karuna Therapeutic’s ongoing Phase III ARISE clinical trial, KarXT could be the first approved adjunctive therapy for the treatment of schizophrenia.”

With a primary completion date of November 2023, GlobalData forecasts that KarXT will be launched as an adjunctive therapy in the US in Q3 2025.

Wong adds: “Neurocrine Biosciences’s Ingrezza (valbenazine tosylate) and Acadia Pharmaceuticals’s Nuplazid (pimavanserin tartrate) are two notable late-stage pipeline products that are also being developed as adjunctive therapies for schizophrenia and are set to compete with KarXT. However, as they both are anticipated to launch in the US in Q4 2025 for adjunctive use in patients with inadequately controlled symptoms of schizophrenia, GlobalData expects KarXT to have a first-to-market advantage.”