Presentation of Ingezza capsules data on tardive dyskinesia improvement regardless of baseline antipsychotic use at 2023 Psych Congress Elevate – Neurocrine Biosciences

Neurocrine Biosciences, Inc. presented findings from a meta-analysis of three long-term studies evaluating Ingrezza (valbenazine) capsules that demonstrated substantial and sustained improvements in tardive dyskinesia (TD) in adults with or without concomitant antipsychotic therapy. The data (Poster #4) were presented at 2023 Psych Congress Elevate in Las Vegas.

The analysis of the three studies (KINECT 3, KINECT 4, and J-KINECT) demonstrated that treatment with once-daily Ingrezza (40 mg or 80 mg) resulted in substantial and sustained TD improvement through week 48 as measured by the Abnormal Involuntary Movement Scale (AIMS) total score, with no meaningful differences between study completers taking antipsychotics at baseline (AP+) and those who were not (AP-). Upon withdrawal of Ingrezza, both subgroups experienced a return toward baseline severity of TD symptoms, demonstrating the potentially persistent nature of TD, even in patients no longer taking antipsychotic therapy. Researchers concluded that continuous treatment with Ingrezza to manage TD may be warranted irrespective if they were on concurrent antipsychotic therapy.

“TD may persist even after patients are no longer taking antipsychotic therapy,” said Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. “These data from three long-term studies reinforce the continuing value of Ingrezza in TD management, regardless of antipsychotic status.”

Key results from the meta-analysis demonstrated the following : i .Mean baseline AIMS scores within each study ranged from 7.9 to 14.9 in the subgroup taking antipsychotics at baseline (AP+) and from 10.9 to 14.5 in the subgroup not taking antipsychotics at baseline (AP-) ii. Mean changes from baseline in AIMS total scores within the combined group were similar between the AP+ and AP- subgroups and indicated substantial TD improvements with Ingrezza 40 mg and 80 mg at week 48 (AP+, -6.1; AP-, -6.5) iii. Both AP+ and AP- subgroups within the combined group experienced a return toward baseline severity at week 52, four weeks after Ingrezza 40 mg or 80 mg withdrawal (AP+, -2.1; AP-, -1.4).

Additional presentations include : Global Improvements and Psychiatric Stability in Adults With Tardive Dyskinesia and Mood Disorder: Post Hoc Analyses of Two Long-Term Valbenazine Studies (Poster #3).

About the KINECT 3 Phase III Study : KINECT 3 is a Phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study, in which 234 participants with moderate to severe TD and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder) received six weeks of once-daily Ingrezza (40 mg or 80 mg capsules) or placebo (participants randomized to 80 mg started on 40 mg for one week). Subsequent to the completion of the six-week placebo-controlled dosing, participants receiving Ingrezza continued on their current dose, and placebo participants were randomized to receive either once-daily 40 mg or once-daily 80 mg of Ingrezza, through week 48 (42-week blinded treatment extension period; placebo participants randomized to 80 mg started on 40 mg for one week), followed by a four-week drug-free washout. Dose reduction to 40 mg was allowed for participants who were unable to tolerate the 80 mg dose. Patients were discontinued if the new dose was not tolerated.

The study met its primary endpoint of change-from-baseline in AIMS at week six in the 80 mg once-daily dosing group compared to placebo, as assessed by expert central blinded video raters. The mean change from baseline to week six in the AIMS rating was -3.2 for the 80 mg once-daily group as compared to -0.1 in the placebo group (P>0.0001). Sustained TD improvements were seen with Ingrezza 40 mg and 80 mg through week 48.

Ingrezza was generally well tolerated throughout 48 weeks of treatment. The most common adverse reactions ( greater than five percent and twice the rate of placebo) during the six-week, double-blind, placebo-controlled phase was somnolence with the frequency of adverse events being similar among all treatment groups. Treatment-emergent adverse events (TEAEs) were consistent with those of prior studies. There were no drug-drug interactions identified in participants who were utilizing a wide range of psychotropic and other concomitant medications, and participants generally remained psychiatrically stable throughout the study.

About the KINECT 4 Phase III Study : KINECT 4 is a Phase III, open-label study, in which 163 participants with moderate to severe TD and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder) received 48 weeks of open-label treatment with once-daily Ingrezza (40 mg or 80 mg capsules) followed by a four-week washout. Dosing was initiated at 40 mg/day in all participants, with escalation to 80 mg/day at week 4 based on effectiveness and tolerability. Dose reduction to 40 mg was allowed in participants who could not tolerate the 80 mg dose. Patients were discontinued if the new dose was not tolerated.

Participants experienced TD improvements during long-term treatment, as demonstrated by mean change from baseline to week 48 in AIMS total score (sum of items 1-7, evaluated by site raters) with Ingrezza 40 mg/day (-10.2) or 80 mg/day (-11.0). Consistent with previous studies, Ingrezza was generally well tolerated. After week four, TEAEs that occurred in greater than 5 percent of all participants (combined dose groups) were urinary tract infection (8.5 percent) and headache (5.2 percent). Changes from baseline in psychiatric stability, vital signs, electrocardiogram parameters and laboratory test values were generally small and not clinically significant.

About J-KINECT Phase II and III Studies : In 2015, Mitsubishi Tanabe Pharma Corporation (MTPC) exclusively licensed the development and commercialization rights for valbenazine in Japan and certain other Asian countries with Neurocrine Biosciences. MTPC conducted J-KINECT, the Phase II/III, multicenter, randomized, double-blind, placebo-controlled study to confirm the efficacy and safety of valbenazine 40 mg or 80 mg administered once daily for up to 48 weeks in adult patients with moderate or severe tardive dyskinesia (TD). The study showed a significant improvement in the primary efficacy endpoint of the mean change from baseline in the Abnormal Involuntary Movement Rating Scale (AIMS) total score at week 6 of treatment with valbenazine compared to placebo. The persistence of efficacy was also shown in the AIMS total score at week 48. In addition, valbenazine was also well tolerated. The incidence of adverse events was highest in the 80 mg group and included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia and tremor. In 2021, MTPC received approval of valbenazine capsules 40mg for the treatment of TD in Singapore, Thailand, South Korea, and Indonesia, followed by approval in Japan and Malaysia in 2022.