Brilaroxazine (RP5063) Clinical Experience in Schizophrenia: "A New Option to Address Unmet Needs"

Abstract

Schizophrenia is a condition comprising of both treatment and comorbidity factors that both complicate its management and present multiple unmet needs. Brilaroxazine (RP5063), a dopamine (D)/serotonin (5-HT) modulator, possesses a broad in vitro pharmacology profile against D 2/3/4 and 5-HT 1A/2A/2B/6/7 receptors, nicotinic acetylcholine (α 4 β 2 ) receptors, and the serotonin transporter. In Phase 1 and 2 clinical experience in healthy volunteers, patients with schizophrenia and schizoaffective disorder, brilaroxazine was well tolerated, with the repeated 100 mg oral dose as the maximum tolerated dose. Investigators observed no cardiometabolic, cardiovascular, prolactin, or neurologic complications. Adherence in Phase 2 was good with discontinuation rates generally less than placebo. In a Phase 2 evaluation of patients with acute exacerbations in schizophrenia and schizoaffective disorders, brilaroxazine met its primary endpoint of significance versus placebo for Total Positive and Negative Symptom Scale (PANSS) Score at Day 28 as compared to baseline. In Phase 1 multi-dose pharmacodynamic evaluation, brilaroxazine displayed clinical activity in patients with stable disease and a PANSS greater than 50, as early as Day 10 of treatment. Pharmacokinetic analyses demonstrated brilaroxazine to have a substantial and relatively rapid oral absorption, linear (dose proportional) increases in maximum concentration (C max ) and area under the curve (AUC), lack of excessive accumulation, and a relatively long terminal half-life of about 60 hours. Early clinical findings with brilaroxazine in schizophrenia and schizoaffective disorders indicate that this compound appears to be effective, well tolerated, and possess a straightforward once-daily dosing pharmacokinetic profile.

Comparative Clinical and Neuropsychological Characteristics in Schizophrenia and Schizophrenia–Obsessive-Compulsive Disorder Patients

“…In the schizophrenia + OCD group, it was found that the number of female patients was significantly lower and the number of male patients was significantly higher. Although there are studies in the literature reporting that OCS are significantly higher in men than women (Baek et al, 2020; Cheng et al, 2019), many studies have not found sex difference in terms of OCS (Bhat et al, 2018; Kazhungil et al, 2017). There are studies in the literature reporting that adult OCD shows an equal distribution in men and women (Bhat et al, 2018), as well as studies reporting higher frequency in women (Sa et al, 2009).…”

“…Although there are studies in the literature reporting that OCS are significantly higher in men than women (Baek et al, 2020; Cheng et al, 2019), many studies have not found sex difference in terms of OCS (Bhat et al, 2018; Kazhungil et al, 2017). There are studies in the literature reporting that adult OCD shows an equal distribution in men and women (Bhat et al, 2018), as well as studies reporting higher frequency in women (Sa et al, 2009). The result of our study is consistent with the results of the study reporting that OCS are more common in male patients with schizophrenia in the literature.…”

Brilaroxazine lipogel displays antipsoriatic activity in imiquimod‐induced mouse model

“…Such brilaroxazine Lipogel delivery characteristics offer potential for psoriasis, but this promise needs translation from animals to the clinic. Currently, brilaroxazine's clinical development program involves schizophrenia as a lead indication in clinical phase 3 studies for its oral formulation with plans to further expand the portfolio in bipolar disorder, major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), pulmonary arterial hypertension (PAH), and idiopathic pulmonary hypertension (IPF) as rare disease indications 52–54 These directions may offer a connection to psoriasis. First, psoriasis appears relevant as there appears to be a relationship between patients with mental illness with psoriasis, which may occur in as high as 36% of such patients 5–9 .…”

Brilaroxazine (RP5063), a Novel Serotonin-Dopamine Stabilizer, Displays Antipsychotic Efficacy in Rodents

“…Schizophrenia is a complex, chronic, and debilitating psychiatric syndrome affecting approximately 1% of the world's population 1 . This disorder is characterized by a complex mix of positive symptoms, negative symptoms, mood symptoms, cognitive impairment and immune system abnormalities 2,3 . The pathobiology of schizophrenia involves an imbalance of dopamine (D) and serotonin (5-HT) levels in the brain due to a dysfunctional D/5-HT signaling system.…”