Abilify Asimtufii (aripiprazole two-month) / Lundbeck, Otsuka - LARVOL DELTA

A review of clinical applications of pharmacokinetic simulations for a 2-month long-acting injectable formulation of aripiprazole. (PubMed, Curr Med Res Opin) - "Aripiprazole 2-month ready-to-use (Ari 2MRTU) is a long-acting injectable antipsychotic that was approved for use in Europe in March 2024, for the maintenance treatment of schizophrenia in adult patients stabilized with aripiprazole; it is administered via gluteal intramuscular injection once every two months...Various simulations conducted across 8 weeks (representing the first dosing interval), or 32 weeks (representing maintenance dosing) demonstrated an aripiprazole exposure profile for Ari 2MRTU that was similar to aripiprazole once-monthly (AOM), but with an extended dosing interval...The availability of Ari 2MRTU extends the range of options for the maintenance treatment of schizophrenia in Europe. Ari 2MRTU may provide adherence benefits due to its extended dosing interval and the option to initiate treatment using a two-injection start regimen, which does not require 14 days of overlapping oral supplementation."

Journal • PK/PD data • Review • CNS Disorders • Psychiatry • Schizophrenia

Health Canada Approves Otsuka and Lundbeck's (Pr)ABILIFY ASIMTUFII (aripiprazole), the First-and-Only, Once-Every-Two-Months, Long-Acting Injectable (LAI) Treatment for Schizophrenia and for Maintenance Monotherapy of Bipolar I Disorder in Adults (Canada Newswire) - "Otsuka Pharmaceutical Canada Inc. (Otsuka) and Lundbeck Canada Inc. (Lundbeck) announce that Health Canada has issued a Notice of Compliance for ABILIFY ASIMTUFII (aripiprazole prolonged release injectable suspension) for intramuscular use, a once-every-two-months treatment for schizophrenia and maintenance monotherapy of bipolar I disorder in adults....ABILIFY ASIMTUFII, a long-acting treatment, offers continuous delivery of medication, which may help those living with schizophrenia or bipolar I disorder."

Canada approval • Bipolar Disorder • Schizophrenia

Use of an injection of aripiprazole given once every 2 months (Abilify Asimtufii®) in people with bipolar I disorder: a Plain Language Summary of Publication. (PubMed, Ther Adv Psychopharmacol) - "The purpose of this summary is to explain key findings from a study that included people with bipolar I disorder, as described in two separate articles (see the 'Further Information' section for more details). The study compared a new formulation of aripiprazole, given as an injection once every 2 months, with a once‑monthly injection of aripiprazole."

Journal • Review • Bipolar Disorder • CNS Disorders • Psychiatry

Aripiprazole 2-month ready-to-use: a novel long-acting injectable antipsychotic formulation for administration once every 2 months (ECNP 2024) - "Until recently, aripiprazole has been available in a daily oral formulation and as an extended-release, once-monthly formulation for intramuscular (IM) injection (aripiprazole once-monthly 400 mg [AOM 400]). Ari 2MRTU is a novel LAI formulation of aripiprazole monohydrate for gluteal IM administration that comes in a ready-to-use syringe and does not require reconstitution. Increasing the dosing interval to 2 months has the potential to reduce the treatment burden for patients and clinicians."

CNS Disorders • Psychiatry • Schizophrenia • CYP3A4 • DRD2

Population Pharmacokinetics and Dosing Simulations for Aripiprazole 2-Month Ready-to-Use Long-Acting Injectable in Adult Patients With Schizophrenia or Bipolar I Disorder. (PubMed, Clin Pharmacol Drug Dev) - "A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once-monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI). Additional simulations accounted for missed/delayed doses, cytochrome (CYP) 2D6 metabolizer status, and concomitant use of CYP2D6 or CYP3A4 inhibitors. Overall, simulations across a variety of scenarios demonstrated an Ari RTU LAI pharmacokinetic exposure profile that was comparable to AOM, with a longer dosing interval."

Journal • PK/PD data • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Development of a Population Pharmacokinetic Model to Describe the Pharmacokinetics of Aripiprazole 2-Month Ready-To-Use, a Novel Long-Acting Injectable Formulation of Aripiprazole for Administration Once Every 2 Months (SIRS 2024) - "Ari 2MRTU 960 will offer an extended dosing interval versus aripiprazole once-monthly 400 mg (AOM 400). A 3-compartment model with linear elimination and different absorption models for each formulation best described the data. Absorption of the Ari 2MRTU formulation was modeled by a parallel zero-order and lagged first-order process that accounted for an identified double peak in plasma concentrations of aripiprazole post-administration of Ari 2MRTU. All disposition parameters were shared between the formulations except Vc/F (oral and AOM formulations, 93.4 L; Ari 2MRTU formulation, 2035 L); the different Vc/F value for the Ari 2MRTU formulation was attributed to the terminal half-life being absorption driven."

Clinical • PK/PD data • CNS Disorders • Schizophrenia

Aripiprazole 2-Month Ready-To-Use: A Novel Long-Acting Injectable Antipsychotic Formulation for Administration Once Every 2 Months (SIRS 2024) - "Background: Schizophrenia and bipolar I disorder (BP-I) are chronic mental health conditions that require maintenance pharmacological treatment to ensure symptom control. Ari 2MRTU has been shown to be generally well tolerated; investigators’ assessments of the injection site reflected minimal reactions in adults with schizophrenia or BP-I. Ari 2MRTU is a prolonged-release suspension for injection in a single-use pre-filled syringe; it is provided in its final container, with no dilution or reconstitution required prior to administration. Each Ari 2MRTU pre-filled syringe contains 960 mg of aripiprazole monohydrate (total volume 3.2 mL) for administration once every 2 months, providing a dose of aripiprazole that is comparable with a monthly dose of AOM 400."

CNS Disorders • Schizophrenia • CYP2D6 • CYP3A4 • DRD2

Pharmacokinetic Simulations of Aripiprazole 2-Month Ready-To-Use Long-Acting Injectable to Inform Administration in Adult Patients With Schizophrenia (SIRS 2024) - "Background: Ongoing symptom control in patients with schizophrenia relies on long term, consistent antipsychotic treatment. Across multiple simulated initiation scenarios, Ari 2MRTU 960 resulted in aripiprazole 2024 Congress of the Schizophrenia International Research Society concentrations that were comparable to AOM 400, and within the established aripiprazole therapeutic window (95–534 ng/mL) (2,3). This was the case for: • initiation of Ari 2MRTU 960 after a direct transition from AOM 400 • initiation of Ari 2MRTU 960 plus 14 days of overlapping oral aripiprazole 10 or 20 mg/day following stabilization on oral aripiprazole 10 or 20 mg/day, and • initiation of Ari 2MRTU 960 on Day 28 after administration of AOM 400 on Day 0 plus 14 days of overlapping oral aripiprazole 20 mg/day following stabilization on oral aripiprazole 20 mg/day. In maintenance scenarios, median trough concentrations were 191, 144, 110, and 80.1 ng/mL after an Ari 2MRTU 960 dosing delay of 2, 4,..."

Clinical • PK/PD data • CNS Disorders • Schizophrenia • CYP2D6 • CYP3A4

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU): review of its possible role in schizophrenia therapy. (PubMed, Curr Med Res Opin) - "Additional advantages of longer injection intervals are more room for non-medication-related communication between healthcare professionals and patients, patient and physician preferences, reduced caregiver burden and easier transitioning from inpatient to outpatient treatment. Taken together, since aripiprazole may be a good treatment choice for many patients based on its favorable safety and tolerability profile, and given the advantages of LAI treatment over oral treatment and the advantages of reduced dosing frequency, Ari 2MRTU 960 may become an important treatment option for many clinically stable patients with schizophrenia."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

A Trial of Multiple-doses of Aripiprazole in Adults With Schizophrenia or Bipolar 1 Disorder (clinicaltrials.gov) - P1/2 | N=266 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Phase classification: P1b ➔ P1/2

Phase classification • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Population pharmacokinetic modelling for aripiprazole 2-month ready-to-use, a novel long-acting injectable formulation of aripiprazole for use in adults with schizophrenia (ECNP 2023) - "Ari 2MRTU 960 will offer an extended dosing interval versus aripiprazole once-monthly 400 mg (AOM 400). The final popPK model was considered fit for purpose, adequately describing aripiprazole PK following administration of Ari 2MRTU 960. The model also established estimates for key popPK parameters and identified sources of variability in drug exposure. The model will be used to perform simulations to support dosing of Ari 2MRTU 960 across multiple realistic clinical scenarios."

Clinical • PK/PD data • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Safety and efficacy of aripiprazole 2-month ready-to-use 960 milligram in adult patients with schizophrenia (ECNP 2023) - P1b | "Background: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months [1]. In patients with schizophrenia, administration of Ari 2MRTU 960, as compared with AOM 400, was generally well tolerated, and clinical stability was maintained during the study."

Clinical • Bipolar Disorder • CNS Disorders • Pain • Psychiatry • Schizophrenia

Safety and Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg: Secondary Analysis of Outcomes in Adult Patients With Schizophrenia in a Randomized, Open-label, Parallel-Arm, Pivotal Study. (PubMed, J Clin Psychiatry) - P1b | "Objective: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. Ari 2MRTU 960 was well tolerated in clinically stable patients with schizophrenia, with efficacy similar to AOM 400. Trial Registration: ClinicalTrials.gov identifier: NCT04030143."

Clinical • Journal • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Safety and efficacy of aripiprazole 2-month ready-to-use 960 mg: secondary analysis of outcomes in adult patients with bipolar I disorder in a randomized, open-label, parallel-arm, pivotal study. (PubMed, Curr Med Res Opin) - P1b | "Objective: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (p = 0.0169). Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400.Trial registration: ClinicalTrials.gov identifier: NCT04030143."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Pain • Psychiatry • Schizophrenia

Aripiprazole 2-Month Ready-To-Use: A Novel Long-Acting Injectable Antipsychotic Formulation for Administration Once Every 2 Months (ASCP 2023) - "To date, aripiprazole has been available in a daily oral formulation and as an extended release once-monthly formulation for intramuscular (IM) injection (aripiprazole once-monthly 400 mg [AOM 400]). Learning Objectives To understand the potential benefits of Ari 2MRTU, a novel, ready-to-use long-acting injectable formulation of aripiprazole for gluteal intramuscular administration once every 2 months. To understand the key features of the Ari 2MRTU formulation (e.g., provided in a ready-to-use syringe, no reconstitution needed)."

Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia • CYP2D6 • CYP3A4 • DRD2

Pharmacokinetic Simulations of Aripiprazole 2-Month Ready-To-Use Long-Acting Injectable to Inform Administration in Adult Patients with Schizophrenia or Bipolar-I Disorder (ASCP 2023) - "Model simulations showed that aripiprazole plasma concentrations over the 2-month dosing interval with Ari 2MRTU 960 were comparable to those observed with AOM 400 administered once-monthly. These data will inform dosing of Ari 2MRTU 960 across the patient and clinical scenarios considered in these simulations, not all of which can be feasibly evaluated in a clinical trial. Learning Objectives To understand the features and potential benefits of aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960), a novel long-acting injectable formulation of aripiprazole monohydrate for gluteal intramuscular administration once every 2 months."

Clinical • PK/PD data • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia • CYP2D6 • CYP3A4

Development of a Population Pharmacokinetic Model to Describe the Pharmacokinetics of Aripiprazole 2-Month Ready-To-Use, a Novel Long-Acting Injectable Formulation of Aripiprazole for Administration once Every 2 Months (ASCP 2023) - "Ari 2MRTU 960 will offer an extended dosing interval versus aripiprazole once-monthly 400 mg (AOM 400). The final popPK model was considered fit for purpose, adequately describing aripiprazole PK following administration of Ari 2MRTU 960. The model also established estimates for key popPK parameters and identified sources of variability in drug exposure. The model will be used to perform simulations to support dosing of Ari 2MRTU 960 across multiple realistic clinical scenarios."

Clinical • PK/PD data • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

FDA Greenlights First Bi-Monthly Injectable for Schizophrenia, Bipolar 1 Disorder (BioSpace) - "Friday, the FDA approved Otsuka and Lundbeck’s extended-release injectable formulation of aripiprazole, now to be marketed as Abilify Asimtufii, for the treatment of schizophrenia or as maintenance therapy for bipolar I disorder...Otsuka and Lundbeck supported Abilify Asimtufii’s FDA bid with data from the pivotal 031-201-00181 trial, which compared its efficacy with another aripiprazole formulation, the 400-mg once-monthly Abilify Maintena, in the same indications...In its approved form, Abilify Asimtufii comes in 960-mg and 720-mg prefilled syringes, both of which are designed to deliver doses that lead to sustained plasma levels of aripiprazole."

Launch US • Bipolar Disorder • CNS Disorders • Psychiatry

FDA Approves Otsuka and Lundbeck’s ABILIFY ASIMTUFII (aripiprazole), the First Once-Every-Two-Months Long-acting Injectable (LAI) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults (Businesswire) - "Otsuka America Pharmaceutical, Inc. (Otsuka) and Lundbeck announce the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for ABILIFY ASIMTUFII® (aripiprazole) extended-release injectable suspension for intramuscular use, a once-every-two-months injection for the treatment of schizophrenia in adults or for maintenance monotherapy treatment of bipolar I disorder in adults....The efficacy of ABILIFY ASIMTUFII is based on the adequate and well-controlled studies of ABILIFY MAINTENA® (aripiprazole) in the treatment of schizophrenia or maintenance treatment of bipolar I disorder in adults. The aripiprazole concentrations of ABILIFY ASIMTUFII were explored in a pharmacokinetic bridging study which was a 32-week, open-label, multiple-dose, randomized, parallel-arm, multicenter study (N=266) in patients living with schizophrenia and bipolar I disorder."

NDA • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

A Randomized, Open-Label, Multiple-Dose, Parallel-Arm, Pivotal Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Aripiprazole 2-Month Long-Acting Injectable in Adults With Schizophrenia or Bipolar I Disorder. (PubMed, CNS Drugs) - P1b | "Ari 2MRTU 960 was generally well tolerated in adults with schizophrenia or BP-I, with a safety profile comparable with that of AOM 400, and aripiprazole exposure equivalent to that with AOM 400 (ClinicalTrials.gov identifier: NCT04030143, registered on 23 July 2019)."

Journal • PK/PD data • Bipolar Disorder • CNS Disorders • Pain • Psychiatry • Schizophrenia

"Otsuka and Lundbeck Announce U.S. FDA Acceptance of New Drug Application for Aripiprazole 2-month, Ready-to-Use, Long-acting Injectable to Treat Schizophrenia and Bipolar I Disorder in Adults https://t.co/ckMgEoL6Y3" (@NewsFromBW)

FDA event • NDA • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Switching From Oral Therapy to Long-Acting Injectables (MD Magazine) - "Christoph Correll, MD: For example, paliperidone has a day 1, day 8, and then 1 month later the injection. Olanzapine pamoate has shorter injection intervals of 2 weekly or higher doses initially. Those do not require oral cotreatment....Similarly, aripiprazole lauroxil has come out with a smaller dispersion formulation where you give 2 injections on day 1 and 1 oral dose of 30 mg, and thereby also obviating the need for oral cotreatment. Currently, risperdal consta, which is given every 2 weeks, requires for the first 3 weeks oral cotreatment with risperidone."

Video • Schizophrenia

Alkermes presents new data from schizophrenia portfolio at Virtual 2020 Congress of the Schizophrenia International Research Society (PRNewswire) - "Alkermes plc (Nasdaq: ALKS) today announced the presentation of new data from its schizophrenia portfolio as part of the virtual 2020 Congress of the Schizophrenia International Research Society (SIRS). New e-posters related to ALKS 3831 (olanzapine/samidorphan), ARISTADA® (aripiprazole lauroxil), and epidemiological schizophrenia data are now posted on the SIRS website..."

P3 data • Retrospective data • CNS Disorders • Schizophrenia

Abilify Maintena 2-month: Regulatory submission for schizophrenia in 2021 (Lundbeck) - Q3 2019 Reuslts

Regulatory

Abilify Maintena: Regulatory submission of 2-month formulation for schizophrenia in 2020 (Lundbeck) - Q1 2019 Results

Regulatory