The Food and Drug Administration (FDA) has approved Abilify Asimtufii^® (aripiprazole extended-release injectable suspension) for the treatment of schizophrenia in adults and as maintenance monotherapy treatment of bipolar I disorder in adults.

Abilify Asimtufii, an atypical antipsychotic, is intended for dosing every 2 months via intramuscular injection in the gluteal muscle. The approval was based on safety and efficacy data from Abilify Maintena (once monthly dosing) trials, as well as findings from an open-label, multiple-dose, parallel-arm phase 1/2 study (ClinicalTrials.gov Identifier: NCT04030143) that included  266 adults with schizophrenia or bipolar I disorder.

Study participants were randomly assigned to receive either Abilify Asimtufii 960mg (n=132) administered every 56 days (total of 4 injections) or Abilify Maintena 400mg (n=134) administered every 28 days (total of 8 injections). Results showed that treatment with Abilify Asimtufii met the primary endpoint demonstrating similar aripiprazole plasma concentrations and comparable efficacy to Abilify Maintena.

Treatment with the every 2-month injectable was found to be safe and well tolerated; no new safety concerns were reported with multiple administrations. The most common adverse reactions reported were increased weight, akathisia, injection site pain, and sedation.

Each dose of Abilify Asimtufii is provided in a single-chamber, prefilled syringe, and is administered by a health care provider. The product is available in 720mg/2.4mL and 960mg/3.2mL dosage strengths.

HealthDay News — Antipsychotics are more often used by older adults receiving home health care (HHC) services with Alzheimer disease and related dementias (ADRD) vs those without ADRD, and their use is associated with worse functional outcomes, according to a study published online September 6 in the Journal of the American Geriatrics Society.

Jinjiao Wang, PhD, RN, from the University of Rochester in New York, and colleagues conducted a secondary analysis of 6684 adults aged 65 years and older, with and without ADRD, receiving care from an HHC agency in 2019 to examine the prevalence and predictors of antipsychotic use and its impact on outcomes among those living with ADRD. The change in the composite activities of daily living (ADL) score from HHC admission to HHC discharge (functional outcome) was measured in 5833 patients, where a positive score indicates improvement and a negative score indicates decline.

The researchers found that among patients with and without ADRD, the point prevalence of antipsychotic use was 17.2 and 6.6%, respectively. Predictors of antipsychotic use among patients living with ADRD included having greater ADL limitations, taking more medications, having behavioral and psychological symptoms, and living alone. Antipsychotic use was associated with having less ADL improvement at HHC discharge among patients living with ADRD.

“Antipsychotic use in persons with dementia is a serious patient safety issue, and it should be regularly reviewed for opportunities of deprescribing, such as dose reduction until discontinuation, whenever possible,” Wang said in a statement.

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HealthDay News — Antipsychotics are increasingly being prescribed to children, according to a study published online January 10 in The Lancet Psychiatry.

Maja R. Radojčić, PhD, from the University of Manchester in the United Kingdom, and colleagues describe up-to-date trends in antipsychotic prescribing among all children and adolescents aged 3 to 18 years in the Clinical Practice Research Datalink Aurum database, registered in England between January 1, 2000, and December 31, 2019. Data were included for 7,216,791 children and adolescents (48.2% girls and 51.8% boys) who were followed for a median of 4.1 years.

The researchers found that during follow-up, 19,496 (0.3%) participants received 243,529 antipsychotic prescriptions, including 92.7 and 7.3% atypical and typical antipsychotic prescriptions, respectively. From 2000 to 2019, there was an increase in the annual period prevalence of antipsychotic prescriptions from 0.057 to 0.105%, respectively. The period prevalence of all antipsychotic prescriptions increased 3.3% per year on average, and the rate of first prescriptions increased 2.2% per year. For first identified antipsychotic prescriptions, the most likely indications were for autism spectrum disorder, nonaffective psychosis, anxiety disorders, attention-deficit/hyperactivity disorder, depression, and conduct disorders (12.7, 8.6, 7.5, 7.1, 6.4, and 6.1%, respectively).

“Authorities in England should monitor and review the emerging trend we describe of broadening clinical indications for antipsychotic use in young people, as well as possible emerging health inequalities in their use,” the authors write.

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Atypical Antipsychotic Pharmacokinetics

The randomized, double-blind, placebo-controlled, multicenter RECOVER trial (ClinicalTrials.gov Identifier: NCT05184335) evaluated the efficacy and safety of brilaroxazine, a novel serotonin-dopamine signaling modulator, in 412 patients with acute schizophrenia. Study participants were randomly assigned to receive either brilaroxazine at fixed doses of 15mg or 50mg once daily or placebo for 28 days. 

Findings showed a statistically significant and clinically meaningful 10.1-point reduction in Positive and Negative Syndrome Scale (PANSS; primary endpoint) total score with brilaroxazine 50mg vs placebo (-23.9 vs -13.8 points, respectively; P <.001) at week 4.

Statistically significant improvements in key secondary endpoints including positive symptoms (P <.001), negative symptoms (P <.001), NS Marder Factor (P =.003), PANSS social cognition (P <.001), PANSS excitement/agitation (P <.001), personal and social performance (P <.001), and Clinical Global Impressions-Scale score (P <.001) were also observed with the 50mg dose.

As for safety, there were no drug-related or treatment-emergent serious adverse events observed with brilaroxazine. Compared with placebo, no significant changes to body weight, blood glucose levels, lipid levels, or endocrine hormones were reported.

“The RECOVER pivotal results highlight the potentially differentiated therapeutic profile of once-daily brilaroxazine and underscore the potential to address treatment limitations for the 24 million people living with schizophrenia around the world,” said Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. “We expect to report long-term data from our [open-label extension] trial in the fourth quarter of 2024 and initiate a registrational phase 3 RECOVER-2 trial in the first quarter of 2024, which if successful will help support our planned New Drug Application (NDA) submission to the FDA expected in 2025.”

Ulotaront was not found to significantly benefit patients with schizophrenia more than placebo in two phase 3 studies, according to Sumitomo Pharma and Otsuka Pharmaceutical.

The DIAMOND 1 (ClinicalTrials.gov Identifier: NCT04072354) and DIAMOND 2 (ClinicalTrials.gov Identifier: NCT04092686) studies evaluated the safety, efficacy and tolerability of ulotaront, a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT_1A agonist activity, vs placebo in acutely psychotic adults with schizophrenia. The primary endpoint for both studies was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week 6.

In DIAMOND 1, patients (N=435) were randomly assigned to receive ulotaront 50mg/day, 75mg/day, or placebo. Results showed neither ulotaront group was superior to placebo; change from baseline in PANSS total score at week 6 (least squares [LS] mean) was reported to be -16.9 and -19.6 with ulotaront 50mg and 75mg, respectively, and -19.3 with placebo.

In DIAMOND 2, patients (N=464) were randomly assigned to receive ulotaront 75mg/day, 100mg/day, or placebo. Neither treatment group demonstrated a statistically significant improvement compared with placebo; change from baseline in PANSS total score at week 6 (LS mean) was reported to be -16.4 and -18.1 with ulotaront 75mg and 100mg, respectively, and -14.3 with placebo.

According to the Companies, a large placebo effect was observed in both studies, which may have masked the therapeutic effects of ulotaront. “High placebo responses, like those seen in DIAMOND 1 and DIAMOND 2, are well documented in psychiatric clinical studies,” explained Hiroshi Nomura, representative director, president and CEO of Sumitomo Pharma. “The placebo response in DIAMOND 1 was particularly high. These studies were conducted throughout the COVID-19 pandemic and initial analyses of these data suggest an impact of COVID-19 on the placebo responses that were seen. We continue to work closely with Otsuka and analyze the data to determine our next steps and plan to discuss with the US FDA how to proceed based on these results.”

In 2019, ulotaront was granted Breakthrough Therapy designation by the FDA for the treatment of schizophrenia. The TAAR1 agonist is also being evaluated as a treatment for generalized anxiety disorder (ClinicalTrials.gov Identifier: NCT05729373) and as an adjunctive therapy for major depressive disorder (ClinicalTrials.gov Identifier: NCT05593029).

Drug-Induced Photosensitivity

The expanded approval was based on data from a phase 3 study (ClinicalTrials.gov Identifier: NCT04819776) that evaluated the efficacy and safety of iloperidone, an atypical antipsychotic, in 414 adults with a history of bipolar I disorder who had a current episode of mania. Patients were randomly assigned 1:1 to receive either oral iloperidone (n=206) or placebo (n=208).

Findings showed patients treated with iloperidone had significantly larger improvements vs placebo based on the change from baseline in the Young Mania Rating Scale (YMRS) total score at week 4 (primary endpoint; treatment difference: -4.0 [95% CI, -5.7, -2.25]; P =.000008). Significant improvements were observed as early as week 2. Secondary endpoints, including change from baseline in the Clinician Global Impression of Severity (P =.0005) and Clinician Global Impression of Change (P =.0002) scores, were also statistically significant. 

The safety profile of iloperidone was found to be consistent with previous trials in patients with schizophrenia. The most common adverse reactions reported were tachycardia, dizziness, dry mouth, increased alanine aminotransferase, nasal congestion, weight gain, and somnolence.

“With over 100,000 patient years of experience, Fanapt is a familiar therapeutic agent that offers flexible dosing with a well-known safety profile,” said Mihael H. Polymeropoulos MD, Vanda’s President, CEO and Chairman of the Board. “This FDA approval gives patients and service providers a new treatment option for managing bipolar I disorder.”