MedPath

Risperidone

Generic Name
Risperidone
Brand Names
Perseris, Risperdal, Rykindo, Uzedy, Okedi
Drug Type
Small Molecule
Chemical Formula
C23H27FN4O2
CAS Number
106266-06-2
Unique Ingredient Identifier
L6UH7ZF8HC
Background

Risperidone is a second-generation antipsychotic (SGA) medication used in the treatment of a number of mood and mental health conditions including schizophrenia and bipolar disorder. It is one of the most widely used SGAs. Paliperidone, another commonly used SGA, is the primary active metabolite of risperidone (i.e. 9-hydroxyrisperidone).

Schizophrenia and various mood disorders are thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. Risperidone is thought to reduce this overactivity through inhibition of dopaminergic D2 receptors and serotonergic 5-HT2A receptors in the brain.

Risperidone binds with a very high affinity to 5-HT2A receptors, approximately 10-20 fold greater than the drug's binding affinity to D2 receptors, and carries lesser activity at several off-targets which may responsible for some of its undesirable effects.

Indication

Risperidone is indicated for the treatment of schizophrenia and irritability associated with autistic disorder. It is also indicated as monotherapy, or adjunctly with lithium or valproic acid, for the treatment of acute mania or mixed episodes associated with bipolar I disorder.

Risperidone is additionally indicated in Canada for the short-term symptomatic management of aggression or psychotic symptoms in patients with severe dementia of the Alzheimer type unresponsive to nonpharmacological approaches.

Risperidone is also used off-label for a number of conditions including as an adjunct to antidepressants in treatment-resistant depression.

Associated Conditions
Acute Mania, Irritability, Mixed manic depressive episode, Psychosis, Schizophrenia, Acute Manic episode, Agitated psychotic state

FDA Accepts Teva's Applications for UZEDY in Bipolar Disorder and AJOVY for Pediatric Migraines

• Teva Pharmaceutical Industries saw a 14% stock price increase following FDA acceptance of a Supplemental New Drug Application for UZEDY, an extended-release injectable for maintenance treatment of bipolar I disorder. • The FDA also accepted Teva's supplemental Biologics License Application to expand AJOVY's use for preventing migraines in pediatric patients, potentially opening significant new market opportunities. • Despite recent positive regulatory developments, Teva's shares experienced volatility amid broader market concerns about recession potential and proposed pharmaceutical tariffs.

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FDA Accepts Review of UZEDY for Bipolar I Disorder Treatment Extension

• Teva and Medincell announce FDA acceptance of supplemental New Drug Application for UZEDY as a maintenance treatment for bipolar I disorder in adults, expanding from its current schizophrenia indication. • The application leverages existing UZEDY clinical data and previous FDA findings on risperidone formulations for bipolar I disorder, potentially offering a new long-acting injectable treatment option. • If approved, UZEDY would address medication adherence challenges in bipolar I disorder, which affects over 3.4 million U.S. adults and causes significant mood and behavioral disruptions.

MedinCell's Olanzapine LAI Phase 3 Trial Completes, Triggering $5M Milestone Payment from Teva

• MedinCell has successfully completed the SOLARIS Phase 3 trial for their long-acting injectable olanzapine formulation in schizophrenia treatment, reaching a significant development milestone. • The completion of the pivotal study has triggered a $5 million milestone payment from development partner Teva Pharmaceuticals, demonstrating continued progress in the program. • The companies are advancing towards U.S. regulatory submission, aiming to address an important unmet need in schizophrenia treatment through this novel long-acting formulation.

Lyndra Therapeutics and Thermo Fisher Partner to Advance Long-Acting Oral Therapies

• Lyndra Therapeutics and Thermo Fisher Scientific have entered a strategic collaboration to advance Lyndra's long-acting oral therapies. • Thermo Fisher will provide global clinical research and commercial manufacturing services for Lyndra, including its lead product, oral weekly risperidone (LYN-005). • LYN-005 demonstrated efficacy compared to daily Risperdal in a Phase III pivotal study, with a safety study planned for early 2025. • The collaboration leverages Thermo Fisher’s Accelerator Drug Development services and aims to bring groundbreaking, long-acting oral therapies to patients.

Schizophrenia Market Set for Strong Growth, Driven by Novel Therapies

• The schizophrenia market is expected to grow significantly, driven by the launch of novel therapies and increased diagnosis rates. • Long-acting injectables (LAIs) are gaining traction despite higher costs, offering an alternative to oral antipsychotics. • The US dominates the schizophrenia market due to a large patient population and high drug costs. • Emerging treatments like Cobenfy, evenamide, Ingrezza, and iclepertin aim to address unmet needs in managing both positive and negative symptoms.

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• Teva's TEV-'749, a long-acting injectable, significantly improved social functioning and quality of life in schizophrenia patients in the Phase III SOLARIS trial. • The SOLARIS study evaluated three doses of TEV-'749, showing improvements by week 8 compared to placebo in social functioning and quality of life. • TEV-'749 met the primary endpoint in September, demonstrating significant improvements in PANSS total score from baseline to week 8. • The drug may offer a long-acting olanzapine option without the risk of Post-Injection Delirium/Sedation Syndrome (PDSS), an advancement for schizophrenia treatment.

Teva's TEV-'749 Shows Promise in Improving Social Functioning in Schizophrenia Patients

• Teva's TEV-'749, a long-acting injectable olanzapine, demonstrated significant improvements in social functioning and quality of life in schizophrenia patients after eight weeks. • The Phase 3 SOLARIS trial indicated that TEV-'749 has a safety profile consistent with existing oral olanzapine formulations, with no new safety concerns identified. • In vitro and Phase 1 data suggest that TEV-'749's drug delivery system effectively minimizes the risk of Post-Injection Delirium/Sedation Syndrome (PDSS). • Real-world data on Teva's Uzedy (risperidone) showed high adherence rates among schizophrenia patients with unmet social needs, highlighting its potential benefits.

Teva's Olanzapine LAI Shows Positive Phase 3 Results for Schizophrenia

• Teva presented Phase 3 SOLARIS trial data showing Olanzapine LAI significantly improved social functioning and quality of life in schizophrenia patients. • The study reported no cases of Post-Injection Delirium/Sedation Syndrome (PDSS) with Medincell's subcutaneous delivery technology. • Real-world data on UZEDY demonstrated high adherence rates among schizophrenia patients with social vulnerabilities. • UZEDY's usage data highlights the need for innovative treatments to address the challenges faced by individuals with schizophrenia.

Teva's TEV-'749 Shows Promise in Improving Social Functioning in Schizophrenia Patients

• Teva's TEV-'749, a subcutaneous olanzapine injection, demonstrated significant improvements in social functioning and quality of life in schizophrenia patients in the Phase 3 SOLARIS trial. • The SOLARIS trial showed statistically significant improvements in Personal and Social Performance Scale scores with TEV-'749 compared to placebo (p<0.05) across multiple doses. • Real-world data analysis of UZEDY (risperidone) showed high adherence rates among schizophrenia patients with social needs, highlighting the importance of addressing social determinants of health. • TEV-'749 drug delivery technology resulted in no Post-Injection Delirium/Sedation Syndrome (PDSS) events to date, suggesting a potentially safer long-acting injectable option.

Teva's TEV-'749 Shows Promise in Improving Social Functioning in Schizophrenia Patients

• Teva's TEV-'749, a subcutaneous long-acting injectable olanzapine, demonstrated significant improvements in social functioning and quality of life in adults with schizophrenia in the Phase 3 SOLARIS trial. • The SOLARIS trial showed statistically significant improvements in the Personal and Social Performance Scale and Schizophrenia Quality of Life Scores compared to placebo. • Real-world analyses of UZEDY (risperidone) showed high adherence rates among adults with schizophrenia, particularly those with unmet social needs like housing instability and food insecurity.

Uzedy Demonstrates Reduced Relapse Risk in Schizophrenia Patients

• New data presented at the ECNP Congress show Uzedy, a risperidone extended-release injectable, significantly reduces relapse risk in adults with schizophrenia compared to placebo. • Pharmacokinetic analysis suggests switching to Uzedy 4 weeks after the final dose of once-monthly RBP-7000 results in comparable drug exposure. • Simulation models support switching to Uzedy at 100 mg (once-monthly) or 200 mg (once-every-2-months) from 120 mg of once-monthly RBP-7000. • The availability of different dosing options allows healthcare professionals to better tailor treatment to individual patient needs and preferences.

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Teva's TEV-749 Shows Promise in Schizophrenia Treatment with No PDSS Incidence

• Teva's TEV-749, a once-monthly subcutaneous olanzapine injection, significantly improved schizophrenia symptoms in a Phase 3 trial, meeting its primary endpoint. • The SOLARIS trial demonstrated statistically significant improvements in PANSS, CGI-S, and PSP scores compared to placebo at week 8 across three dosing groups. • Notably, no cases of post-injection delirium/sedation syndrome (PDSS) were observed, a significant advantage over existing long-acting olanzapine treatments. • The safety profile of TEV-749 was consistent with oral olanzapine, with long-term safety data expected in the first half of 2025.

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• The FDA has approved Cobenfy (xanomeline and trospium chloride) as the first new class of drug for schizophrenia in over 30 years, offering a novel approach to treatment. • Cobenfy targets muscarinic receptors, unlike traditional antipsychotics that focus on dopamine, potentially reducing side effects like weight gain and movement disorders. • Clinical trials demonstrated Cobenfy significantly reduced schizophrenia symptoms compared to placebo, marking a transformative moment in managing this challenging condition. • Expected to launch in late October, Cobenfy offers a new option for adults with schizophrenia, with ongoing studies exploring its potential in Alzheimer's psychosis and other conditions.

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• A New Jersey jury initially awarded $750 million in punitive damages against Johnson & Johnson in a talc-cancer case, later reduced to $187 million due to state law limitations. • Four plaintiffs who developed cancer after using J&J's talc products were previously awarded $37 million in compensatory damages in the same trial. • J&J's CEO Alex Gorsky made his first-ever jury trial appearance regarding talc litigation, while the company faces approximately 16,000 talc-related lawsuits amid ongoing safety concerns.
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