2025 Schizophrenia Insights: Ending the Year With Positive Data

As 2025 comes to a close, we wanted to highlight some of the most recent research and study data on schizophrenia to help keep you informed about novel treatments and the latest insights from conference presentations.

Phase 3 Data on Novel Digital Therapeutic: CT-155 for Negative Symptoms in Schizophrenia

New phase 3 data from the CONVOKE study showed that treatment with CT-155 led to statistically significant reductions in negative symptoms in patients with schizophrenia.

CONVOKE, a multicenter, double-blind study, included adult participants with schizophrenia (N = 464) who were stabilized for positive symptoms but experiencing negative symptoms. Participants were randomly assigned to receive standard-of-care therapy, along with either digital therapeutics (CT-155; BI 3972080) or a sham digital intervention. Participants, most of whom were also on an antipsychotic, were followed for 16 weeks. Investigators examined the change in experiential negative symptoms from baseline, as measured by the Clinical Assessment Interview for Negative Symptoms, Motivation, and Pleasure Scale (CAINS-MAP).

“The CAINS-MAP is a second-generation assessment that examines the core deficits that matter to patients and their families,” Abhishek Pratap, PhD, said during a presentation at the 38th Annual European College of Neuropsychopharmacology Congress in Amsterdam, The Netherlands.

Pratap added that the CONVOKE trial was “as rigorous as any drug trial.” Pratap is the global evidence lead for Boehringer Ingelheim, the company developing CT-155, an adjunct faculty member at the University of Washington, Seattle and Boston University, as well as a visiting research fellow at King’s College London.

Treatment with CT-155 resulted in a 6.8-point improvement on the CAINS-MAP vs 4.2 for the control arm, showing statistical significance via Cohen d effect size of –0.36 (P = .0003). Moreover, almost three-quarters of the patients in both the CT-155 group and the control group (70.4% and 76.5%, respectively) used the app through the end of week 15, demonstrating high engagement.

“Seven of 10 [participants] across both arms were using their app on day 105, which is the last day when the active modules in the app stopped. I have not seen anything in literature [like that] so far,” Pratap said. “This is completely a sea change in that regard. [These are] extremely encouraging data for us to see.”

CT-155 demonstrated a good safety profile, with no serious adverse effects and no trial discontinuations associated with it; however, there were 2 discontinuations in the control group.

“One of 2 patients with schizophrenia continues to have nontreated negative symptoms, making negative symptoms a huge unmet need,” Pratap said. “This is where I believe psychosocial interventions can help bolster real-world skills to help them cope with these deficits.”

Although negative symptoms of schizophrenia contribute to poor outcomes, evidence-based psychosocial interventions can improve negative symptoms and quality of life for patients. Unfortunately, access is often an obstacle, and adherence can be tricky. Pratap explained that digital therapeutics have the potential to address the unmet needs and accessibility issues.

“On every 2 of 3 days—or 7 of 10 days, depending on how you look at it—patients are logging in and completing activities,” he said of the trial results. Data indicated that, on average, patients spent approximately 8 minutes per day on the digital intervention, which is roughly equivalent to 1 hour of psychotherapy per week, addressing negative symptoms, he added.

The digital therapeutic, which received FDA breakthrough device designation in January 2024,² was designed with input from patient groups.

“The design and development of CT-155 was informed by an iterative patient-centered approach with more than 150 people living with schizophrenia, ensuring the therapeutic aimed to address the real-life challenges that people with experiential negative symptoms face, such as lack of motivation, social connection, and ability to feel pleasure,” Austin Speier, chief strategy officer of Click Therapeutics, said in a press release following the presentation.³

“The positive primary end point results observed from the CT-155 phase 3 trial represent an important step forward in exploring how negative symptoms may be better understood, which is an area of long-standing unmet need in mental health care," Gregory W. Mattingly, MD, an associate clinical professor at Washington University in St Louis, Missouri, principal investigator in clinical trials for Midwest Research Group, and founding partner of St Charles Psychiatric Associates, said in a press release. "This research underscores the importance of including innovative approaches in the treatment of schizophrenia. The emergence of prescription digital therapeutics like CT-155, if approved, may hold the potential for patients to access psychosocial intervention from anywhere."³

Pratap noted that data from the phase 3b trial, which is currently underway, should be available by next year.

References

1. Pratap A. Novel therapies symposium: topline results from CONVOKE: a first-in-class phase 3 RCT evaluating a digital therapeutic for experiential negative symptoms of schizophrenia in adults. Presented at: 38th European College of Neuropsychopharmacology Congress; October 11-14, 2025; Amsterdam, The Netherlands.

2. O’Brien E. Prescription digital therapeutic for schizophrenia receives FDA breakthrough device designation. Psychiatric Times. January 4, 2024. https://www.psychiatrictimes.com/view/prescription-digital-therapeutic-for-schizophrenia-receives-fda-breakthrough-device-designation

3. Boehringer and Click Therapeutics present pivotal data for investigational prescription digital therapeutic CT-155 showing a statistically significant reduction in negative symptoms of schizophrenia. Press release. Boehringer Ingelheim. October 13, 2025. Accessed October 13, 2025. https://www.boehringer-ingelheim.com/us/media/press-releases/boehringer-presents-pivotal-data-phase-iii-convoke-study

New Research Shows Valbenazine Leads to Clinically Meaningful Improvements in Tardive Dyskinesia Symptoms

According to a new post-hoc analysis from the phase 3, open-label Kinect 4 study, patients treated continuously for 48 weeks with the 40-mg dose of once-daily valbenazine (Ingrezza) capsules experienced clinically meaningful improvements in tardive dyskinesia (TD) symptoms.¹

Valbenazine is a selective VMAT2 inhibitor approved by the US FDA for the treatment of adults with TD and the treatment of chorea associated with Huntington disease.² Valbenazine offers a therapeutic dose from day 1 with no required titration.

"The Kinect 4 post-hoc analysis demonstrated the rapid, sustained, long-term clinical benefit of treatment with Ingrezza [valbenazine] at the lowest available dose of 40 mg," said Sanjay Keswani, MD, chief medical officer of Neurocrine Biosciences. "Ingrezza [valbenazine] is the only VMAT2 inhibitor that allows patients to start at a therapeutic dose [and] stay at that dose or adjust to 60 mg or 80 mg, based on individual response and tolerability. These findings add to previously published data supporting 40 mg as an effective, long-term treatment option."

The Kinect 4 phase 3, open-label study evaluated the long-term efficacy, safety, and tolerability of valbenazine in adults with TD. Participants in the post-hoc analysis received valbenazine 40 mg once daily for the first 4 weeks, with the option to escalate to 80 mg daily at week 4, based on tolerability and clinical response. From week 4 through week 48, dose reduction from 80 mg to 40 mg was permitted based on individual tolerability.

The analysis included participants in the valbenazine 40 mg group (n = 45), who received 40 mg throughout the entire study, and participants in the valbenazine 80 mg and 40 mg group (n = 11), who increased to 80 mg at week 4 and subsequently reduced to 40 mg. Efficacy was evaluated at all postbaseline visits through the end of treatment (week 48) using clinician- and patient-reported changes in TD severity, as measured by the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD), and Patient Global Impression of Change (PGIC).

Efficacy outcomes demonstrated several clinically meaningful improvements in TD that were sustained throughout the 48-week treatment period in both the valbenazine 40 mg and valbenazine 80 mg and 40 mg groups. At all postbaseline visits from week 4 to week 48, the mean change from baseline in AIMS total score exceeded the minimally clinically important difference threshold, demonstrating rapid and continuous improvements with valbenazine treatment. In participants who received 40 mg throughout the entire study, the percentage meeting the AIMS response threshold (≥ 50% total score improvement from baseline) generally increased over time, with 90% (18/20) of those completing 48 weeks reaching this threshold. The analysis also showed that participants who reduced their dose from 80 mg to 40 mg for tolerability reasons achieved similar therapeutic benefits.

Additionally, from week 8 through week 48, more than half of all participants across both treatment groups met the response threshold for CGI-TD and PGIC, with 90% (18/20) of participants on continuous valbenazine 40 mg treatment being "much improved" or "very much improved" at week 48, per clinician assessment (CGI-TD) and patient self-report (PGIC).

Notably, efficacy outcomes with valbenazine 40 mg were comparable to those achieved with 80 mg in the original Kinect 4 study, and the safety and tolerability of treatment were consistent with the known profile of valbenazine, with no new concerns identified. Most treatment-emergent adverse events were mild or moderate in intensity. The most common adverse effects in individuals with TD are sleepiness and tiredness.

Investigators presented these findings at the American Psychiatric Nurses Association 39th Annual Conference in New Orleans, Louisiana.

References

1. Neurocrine Biosciences presents new KINECT 4 post-hoc analysis demonstrating rapid and sustained therapeutic efficacy of Ingrezza (valbenazine) 40 mg capsules. News release. Neurocrine Biosciences. October 17, 2025. Accessed October 17, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-kinect-4-post-hoc-analysis-demonstrating-rapid-and-sustained-therapeutic-efficacy-of-ingrezza-valbenazine-40-mg-capsules-302586928.html

2. Duerr HA. Ingrezza sprinkle capsules received FDA approval for tardive dyskinesia in adults. Psychiatric Times. April 30, 2024. https://www.psychiatrictimes.com/view/ingrezza-sprinkle-capsules-received-fda-approval-for-tardive-dyskinesia-in-adults

New Data on Lumateperone for Prevention of Relapse in Schizophrenia

According to new research, lumateperone 42 mg showed significant efficacy as maintenance treatment to prevent relapse in adults with schizophrenia.¹ Data on this phase 3 study were presented at the 38th Annual European College of Neuropsychopharmacology Congress in Amsterdam, The Netherlands, by Intra-Cellular Therapies.

Participants in this phase 3 double-blind, placebo-controlled, randomized withdrawal trial were adults aged 18 to 60 years with a DSM-5 diagnosis of schizophrenia for more than 1 year and a Positive and Negative Syndrome Scale (PANSS) score of 70 to 120. All patients initially received lumateperone 42 mg for 18 weeks (6 weeks for the run-in period and 12 weeks for stabilization), and then stable patients were randomly assigned to either treatment or placebo. Randomization was 1:1 double-blind for lumateperone 42 mg or placebo for 26 weeks, or until relapse. A total of 228 patients were stable after the introductory phase, with 114 receiving lumateperone and 114 receiving placebo. Notably, a greater proportion of White patients were stabilized and continued on to the double-blind phase. The primary end point studied was time to first symptom relapse during the blinded phase of treatment. The study also assessed general safety and time to all-cause medication discontinuation, including relapse, during the double-blind phase.

Stabilization after the introductory phase was defined by a PANSS score of 60 or lower, a 20% or greater reduction in PANSS total score from baseline, a Clinical Global Impression Scale-Severity (CGI-S) score of 4 or less, no suicidal ideation, and no tolerability issues. Relapse was defined as 1 or more instances of psychiatric hospitalization or increased psychiatric care, aggressive/violent behavior or self-injury, or suicidal or homicidal ideation; a PANSS total score increase by 30% or greater; a CGI-S score increase by 2 or more points; and a score above 4 on 1 or more of 7 specified PANSS items.

The trial met its primary end point, with lumateperone treatment significantly delaying time to relapse compared with placebo (HR 0.37; 95% CI, 0.22-0.65; P =.0002). Of the 228 patients in the double-blind phase, 130 (58%) completed treatment without relapse. Fewer relapses occurred in the lumateperone group vs placebo (treatment group, n = 18; placebo group, n = 44). Lumateperone was also found to delay time to all-cause discontinuation compared with placebo (P = .0007); the rate of all-cause discontinuation was lower in the lumateperone treatment group compared with the placebo group (treatment group, n = 34; placebo group, n = 60). The most common treatment-emergent adverse effects were headache during both the introductory phase and the double-blind phase. Rates of extrapyramidal symptom–related adverse events were low and similar between treatment and placebo groups. There were no notable changes in prolactin or cardiometabolic parameters.

Lumateperone is a serotonin 5-HT2A receptor antagonist, a dopamine D2 receptor presynaptic partial agonist and postsynaptic antagonist, a D1 receptor–dependent indirect modulator of glutamatergic AMPA and NMDA currents, and a serotonin reuptake inhibitor. Lumateperone is currently approved by the US FDA to treat schizophrenia, as monotherapy for depressive episodes associated with bipolar disorder, and as adjunctive therapy with lithium or valproate.²

These study findings are consistent with previous lumateperone trials demonstrating the drug as safe and well tolerated, indicating benefits for long-term lumateperone treatment for adults with schizophrenia.³

References

1. Durgam S, Earley WR, Kozauer SG. Lumateperone for the prevention of relapse in patients with schizophrenia: results from a double-blind, placebo-controlled, randomized withdrawal, phase 3 trial. Poster presented at: 38th Annual European College of Neuropsychopharmacology Congress; October 11-14, 2025; Amsterdam, The Netherlands.

2. Caplyta. Prescribing information. Intra-Cellular Therapies; 2019. Accessed October 13, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209500s000lbl.pdf

3. Tarzian M, Ndrio M, Chique B, et al. Illuminating hope for mental health: a drug review on lumateperone. Cureus. 2023;15(9):e46143.