Long acting injectable formulation comprising risperidone and biodegradable polymers
Inventors
Wagner, Avia Merenlender • VALITSKY, Anna Elgart • HARARY, Eran
Assignees
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Publication Number
US-12329851-B2
Publication Date
2025-06-17
Expiration Date
Abstract
The present invention is directed to methods of treating psychiatric diseases and disorders comprising administering to a subject in need thereof at a frequency of no more than once every 28 days an injectable formulation comprising risperidone, triblock and diblock copolymers wherein the concentration of the risperidone is 250-400 mg/mL and injection volume is 1 mL or less.
Core Innovation
The invention concerns switching a subject from daily oral risperidone therapy to a long acting injectable risperidone formulation. The method includes orally administering a final dose of the daily oral risperidone therapy and then administering, the next day, a first injectable dose subcutaneously from a pre-filled syringe, after which no further oral risperidone therapy is administered.
The long acting injectable formulation comprises risperidone or a pharmaceutically acceptable salt and specific biodegradable triblock and diblock copolymers. The formulation is constrained by a risperidone concentration of about 300-400 mg/mL, a poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) triblock copolymer, a methoxy-poly(ethylene glycol)-poly(lactic acid) diblock copolymer, specified repeat unit ranges, a ratio constraint between the triblock and diblock copolymers, and insolubility in an aqueous environment.
The switching method specifies multiple daily oral risperidone therapy dose levels, including 2, 3, 4, and 5 mg/day, and corresponding first injectable dose amounts from the pre-filled syringe, including 50, 75, 100, 125, 150, 200, and 250 mg. In documented contexts, the invention is evaluated in a schizophrenia relapse-prevention setting with placebo/vehicle and long acting injectable risperidone administered as once-monthly or once-every-2-months regimens after an oral conversion or stabilization stage.
Claims Coverage
Two independent claims are identified. They share the core switching sequence and the long acting injectable formulation with specified risperidone concentration and biodegradable polymer components, along with explicit oral dose-to-injection dose pairings.
Next-day switching from daily oral risperidone to long acting injectable without further oral risperidone
Orally administering to the subject a final dose of the daily oral risperidone therapy, after which no further oral risperidone therapy is administered; and the next day subcutaneously administering to the subject a first injectable dose from a pre-filled syringe of a long acting injectable risperidone formulation, thereby switching the subject from the daily oral risperidone therapy to the long acting injectable risperidone formulation.
Long acting injectable risperidone formulation with specified concentration and insoluble polymer blend
A long acting injectable risperidone formulation comprising risperidone or pharmaceutically acceptable salt at a concentration of about 300-400 mg/mL, and a biodegradable triblock copolymer with a poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) structure together with a biodegradable diblock copolymer with a methoxy-poly(ethylene glycol)-poly(lactic acid) structure, with specified repeat unit ranges, ratio constraints, and insolubility in an aqueous environment.
Oral dose to first injectable dose pairing for switching method
A switching method wherein 2 mg/day corresponds to 50 mg or 100 mg, 3 mg/day corresponds to 75 mg or 150 mg, 4 mg/day corresponds to 100 mg or 200 mg, and 5 mg/day corresponds to 125 mg or 250 mg.
Overall claim coverage is anchored in the same switching sequence, combined with a formulation defined by risperidone concentration, biodegradable triblock and diblock copolymers with specified repeat-unit ranges and ratio constraints, and explicit pairing of daily oral dose levels to specific first injectable dose amounts.
Stated Advantages
Rapid therapeutic levels within about 24 hours.
Provides statistically significant benefit versus placebo for time to impending relapse.
Reduces relapse risk compared with placebo.
Reduced relapse and reduced time to impending relapse.
Decreased PANSS over time.
Improved post-stabilization performance.
Higher proportions of subjects maintain stability.
Pharmacokinetic comparability across injection sites (abdomen vs upper arm).
Exposure equivalence to daily oral risperidone based on TAM (AUC0-tau) comparisons.
Documented Applications
Switching a subject from daily oral risperidone therapy to a long acting injectable risperidone formulation for psychiatric disorders, including schizophrenia.
Administration regimens that support dosing such as once every 28 days (Q1M), once every two months (Q2M), and once every six weeks (Q6W) as described in the provided partial content.
Relapse-prevention evaluation in schizophrenia, including a Phase 3 relapse-prevention trial comparing placebo/vehicle, once-monthly risperidone long-acting injectable, and once-every-2-months risperidone long-acting injectable after an oral conversion or stabilization stage.
Assessment of stability and remission-related outcomes in schizophrenia using PANSS total score-based criteria and other measures listed in the document.
Subcutaneous injection evaluation including described injection-site interchangeability between an upper arm and an abdomen.
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