Paliperidone Palmitate Six-Monthly (PP6M)

Drug information

Drug's link(s)

Not provided

Generic name

Paliperidone Palmitate Six-Monthly (PP6M)

Brand names

INVEGA HAFYERA®, BYANNLI®

Compound type

Small molecule

Drug class/category

Metabolite of Risperidone (dopamine D2 & serotonin 5HT2A receptor antagonist)

Summary

Paliperidone palmitate administered as a once every six-month long-acting injectable (PP6M) is indicated for the maintenance treatment of schizophrenia in adult patients who are adequately treated with 1-monthly paliperidone palmitate injection at doses of 100 mg or 150 mg (preferably for four months or more) or 3-monthly paliperidone palmitate injection at doses of 350 mg or 525 mg (for at least one injection cycle) and do not require dose adjustment. BYANNLI® and INVEGA HAFYERA® manufactured by Janssen Pharmaceuticals are available in dosage formulations of 700mg and 1000mg. Maximum plasma concentrations of PP6M are achieved after approx. 33-35 days (median Tmax), and are expected to remain in circulation for up to four years at < 1% of the average steady state levels.

Approval status

PP6M was approved under the trade name of INVEGA HAFYERA® in August 2021 by the United States Food and Drug Administration (US FDA) for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA® (PP1M) for at least 4 months OR an every-three-month paliperidone palmitate (PP3M) extended-release injectable suspension (e.g., INVEGA TRINZA®) for at least one three-month cycle. PP6M is also approved by the European Medicines Agency (EMA) under the trade name of BYANNLI® (previously Paliperidone Janssen) for the maintenance treatment of schizophrenia in adult patients who are clinically stable on PP1M or PP3M. The transition to BYANNLI should be initiated in place of the next scheduled dose of paliperidone palmitate injection.

Regulatory authorities

PP6M (1000 mL/5 mL and 750 mg/3.5 mL) has received regulatory approval from 15 Drug Regulatory Authorities across 45 countries, including the FDA, EMA, TGA, MEDSAFE, DH, KMFDS, HSA, NPRA, ISP, INVIMA, Rwanda FDA, SFDA, ALIMS, NMPA, and DCH. The formulation is marketed under the brand name BYANNLI in the European Union (EU) and European Economic Area (EEA). In other regions, including the United States, Australia, New Zealand, Hong Kong, South Korea, Singapore, Malaysia, Chile, Colombia, China, Thailand, and Georgia, it is branded as INVEGA HAYFERA.

Therapeutic area(s)

Mental Health Disorders (incl. schizophrenia, bipolar disorders, Schiz. Aff. Dis.) : "Schizophrenia (naive and previously treated) , Psychotic or manic symptoms of schizoaffective disorde"

Use case(s)

Treatment

Administration route

Intramuscular

Associated long-acting platforms

Aqueous drug particle suspension, Lipid Depot-Nanocrystal technology

Use of drug

Ease of administration

Administered by a nurse
Administered by a specialty health worker
Administered by a community health worker

Frequency of administration

Every 6 months

User acceptance

Not provided

Dosage

Available dose and strength

1,092 mg/3.5 mL ; 1560 mg/5 mL single-dose prefilled syringes

Maximum dose

1560 mg

Recommended dosing regimen

1) Previously treated with PP1M - initial dose - 1092 mg then 1560 mg 2) Previously treated with PP6M - initial dose - 1092 mg then 1560 mg

Additional comments

1. Contraindications: cerebrovascular ADR, neuroleptic malignant syndrome, QT prolongation, Tardive dyskinesia, Orthostatic hypotension, Leukopenia, Hyperprolactinemia & Seizures 2. Drug-drug interactions: Avoid using strong CYP3A4 and/or P-gp inducers

Dosage link(s)

https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/207946s014s015lbl.pdf

Associated compounds, formulations and regimens

Not provided

Associated technologies

Not provided

Additional information

Paliperidone is an atypical antipsychotic drug indicated for the treatment of both schizophrenia & schizoaffective disorder. Paliperidone is the primary active metabolite of risperidone and functions by strongly binding to dopaminergic D2- and serotonergic 5-HT2-receptors and selectively blocking monoamine effects. Although paliperidone is a potent D2-antagonist, it has less of impact on motor function and catalepsy than traditional neuroleptics. Paliperidone palmitate is the palmitate ester prodrug of paliperidone and displays modest solubility in polar solvents. Several long-acting injectable aqueous nanocrystal formulations of paliperidone palmitate are available as once-monthly (PP1M), three-monthly (PP3M) and six-monthly (PP6M) extended-release suspensions for intramuscular injection.

Developer(s)

Originator

Belgium

Johnson & Johnson

Janssen Pharmaceuticals is a subsidiary company of Johnson & Johnson headquartered in Beerse, Belgium. They focus on manufacturing and developing pharmaceutical products for use in areas such as, Immunology, Infectious Diseases & Vaccines, Pulmonary Hypertension, Cardiovascular & Metabolism, Oncology, and Neuroscience.

Drug structure

Scale-up and manufacturing prospects

Scale-up prospects

PP6M is commercially manufactured by Janssen Pharmaceuticals. The PP6M injectable contains a racemic mixture of (+)- and (-)- of paliperidone, and is joined with palmitic acid through an ester linkage. Similarly to paliperidone palmitate once-monthly injectable (PP1M) and three-monthly injectable (PP3M), PP6M is manufactured using Nanocrystal Technology to improve the dissolution properties of paliperidone palmitate, which is highly insoluble in water. PP6M has a bi-annual dosing interval arising from a higher concentration and an increased nanocrystal particle size.

Tentative equipment list for manufacturing

NanoCrystal® Colloidal Dispersion Nanomill™ apparatus.

Manufacturing

NanoCrystal technology enables intrinsically high loading of insoluble drugs as dosage forms consist mostly of pure API packed as a solid crystal, which is the most efficient form possible in relation to weight-to-volume. Paliperidone palmitate particles are dispersed in an aqueous suspension and transformed into smaller nanocrystals through particle-size reduction. These nanocrystals have a greater surface area than the larger original particles, resulting in increased water solubility. This medicinal product does not require any special storage conditions and has a shelf life of two years.

Specific analytical instrument required for characterization of formulation

Digital microscope and scanning electron microscopy (SEM) to determine shape of the particles. Differential scanning calorimetric (DSC) and Fourier transforms infrared spectroscopy (FTIR) for quality control.

Excipients & delivery device(s)

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredient Database (IID) for the specified route of administration

No novel excipient or existing excipient used

Residual solvents used

No residual solvent used

Delivery device(s)

No delivery device

Safety, Efficacy and Evidence Summary

Safety

Not provided

Efficacy

Not provided

Evidence Summary

Not provided

References and relevant studies

Not provided

Description

Methods for improving resuspendability of a paliperidone palmitate extended-release injectable suspension within a syringe

Brief description

Provided are methods for improving resuspendability of a paliperidone palmitate extended-release injectable suspension within a syringe, for reducing a force required for injection of a paliperidone palmitate extended-release injectable suspension, or for reducing the likelihood of incomplete injection of a paliperidone palmitate extended-release injectable suspension comprising maintaining the syringe in a desired orientation during shipping of the syringe that varies from the orientation of the syringe during pre-shipping storage. Also provided are populations of syringes that respectively contain paliperidone palmitate extended release injectable suspension

Representative patent

WO2022112367