麻豆传媒

An investigational long-acting antipsychotic containing risperidone, known as TV-46000, was able to significantly delay time to relapse in patients with schizophrenia, according to the phase III RISE study.

Patients treated with once-monthly injectable TV-46000 saw an 80% reduction in the risk for relapse compared with those who received placebo during the 52-week analysis -- meeting the study's primary endpoint (HR 0.200, 95% CI 0.109-0.367, P<0.0001), reported John Kane, MD, of Northwell Health in Glen Oaks, New York, and colleagues.

Even patients treated with injectable TV-46000 administered once every 2 months saw a 62.5% drop in schizophrenia relapse risk versus placebo (HR 0.375, 95% CI 0.227-0.618, P<0.0001), according to a poster presented at the Psych Congress, held virtually and in San Antonio.

Overall, this equated to a five-fold longer time to impending relapse for those treated with the once-monthly version, and a 2.7-fold longer time to relapse in those treated bimonthly when compared with placebo.

On top of that, a significantly lower proportion of patients experienced a relapse of symptoms by week 24 of the study. While 28% of patients on placebo experienced symptom relapse at this time, only 7% and 11% of those on once-monthly and bimonthly treatment relapsed, respectively.

Meeting another key secondary endpoint, a higher proportion of patients taking TV-46000 maintained stability, defined as early discontinuation or end of treatment. This was achieved by 87% and 80% of patients on once-monthly and bimonthly treatment, respectively, versus 61% of patients on placebo.

"When managing schizophrenia, it is crucial to have treatment options that work to reduce the risk of relapse. As researchers, physicians, and providers, we must work together to address this," Kane said in a statement. "These latest data from the phase III RISE study are quite encouraging for both patients and providers."

The investigational TV-46000 works as a long-acting subcutaneous antipsychotic. It combines risperidone with a novel, copolymer-based drug delivery technology in a suspension allowing for an extended-release injectable administration.

A total of 544 participants were randomized in the intent-to-treat population. To be eligible for the study, patients had to be 13 to 65 years old and have a diagnosis of schizophrenia for over a year with at least one relapse in the previous 24 months. They also all had to have a total Positive and Negative Syndrome Scale (PANSS) score of less than 100 and had to be responsive to antipsychotic treatment other than clozapine in the past year.

During the 12-week pre-treatment stage, patients were stabilized on a dose of 2 to 5 mg/day of oral risperidone. After those 12 weeks, participants were randomized in a 1:1:1 fashion: 183 on once-monthly treatment, 180 on bimonthly treatment, and 179 on placebo.

Those on once-monthly treatment received one dose of the investigational drug -- 50, 75, 100, or 125 mg -- depending on if they were stabilized with risperidone 2 mg, 3 mg, 4 mg, or 5 mg per day prior to randomization.

For those on the bimonthly treatment, doses were double that of the once-monthly group according to the same conversion of oral risperidone (100 mg, 150 mg, 200 mg, or 250 mg).

The treatment was generally well tolerated and had a similar safety profile to oral risperidone. Of the patients on once-monthly and bimonthly treatment, 39% and 42% experienced any treatment-related adverse event versus 26% of the placebo group. Interestingly, a smaller proportion of those on active treatment experienced a serious (4% on once-monthly, 6% on bimonthly, and 8% on placebo) or severe adverse event (3%, 6%, and 7%, respectively). One death occurred in the placebo group, and four deaths occurred in the bimonthly treatment group.

Drug developer Teva Pharmaceuticals announced that the for TV-46000 in August.

Comment