Beyond Clinical Trials: AbbVie’s Julie Adams, Roger McIntyre, and Andrew Cutler on VRAYLAR’s Real-World Impact

Shots:  PharmaShots Viewpoints brings together Julie Adams, MD, of AbbVie; Roger S. McIntyre, MD, of the University of Toronto; and Andrew J. Cutler, MD, of SUNY Upstate Medical University, to examine how real-world evidence is expanding the understanding of VRAYLAR (cariprazine) in major depressive disorder (MDD) and bipolar I depression. Findings from the CReW BP-I and ProACt studies highlight improvements in depressive symptoms, daily functioning, and quality of life.  What does meaningful recovery look like beyond symptom relief? The experts explore improvements in motivation, energy, and anhedonia, including early gains observed as soon as week two in the ProACt study and improvements across depressive symptoms and functioning over 12 weeks in CReW BP-I.  From clinical outcomes to everyday experiences, the discussion explores how real-world evidence can help shape more personalized depression care. The experts highlight its potential to complement clinical trials, capture the impact of treatment on patients’ daily lives, and provide a more comprehensive picture of treatment effectiveness.  Saurabh: Real-world evidence can reveal how a therapy performs beyond the controlled environment of clinical trials. What do the latest CReW BP-I and ProACt findings reveal about the effectiveness of VRAYLAR in everyday clinical practice?   Julie: The findings from these prospective real-world studies show that VRAYLAR (cariprazine) improves depressive symptoms, functioning, and quality of life in major depressive disorder (MDD) and bipolar I (BP-I) patients beyond clinical trials. These studies provide real-world data that its demonstrated efficacy translates to effectiveness in the broader, more clinically complex patient populations healthcare providers treat every day.    Importantly, these findings demonstrate benefits in outcomes that matter most to patients, that is, how they feel and function in their daily lives.   In the prospective CReW BP-I study, patients with BP-I experienced significant improvements in depressive symptoms, functioning, and quality of life after 12 weeks. Interim findings from the prospective ProACt study of adjunctive VRAYLAR also showed improvements in motivation, energy, and anhedonia, or the ability to feel enjoyment, among adults with MDD.   Together, these findings provide additional evidence that VRAYLAR can deliver meaningful, patient-centered benefits beyond a controlled clinical setting.   Saurabh: In CReW BP-I, VRAYLAR was associated with meaningful improvements in depressive symptoms, functioning, and quality of life among patients with bipolar I depression. What does the convergence of these outcomes suggest about achieving meaningful recovery in bipolar depression?   Roger: For patients with bipolar depression, meaningful recovery is about more than reducing depressive symptoms. We also want to see patients functioning better and experiencing improvements in their everyday life. The findings from the prospective CReW BP-I study are encouraging because we saw progress across all three of these areas after 12 weeks of treatment with VRAYLAR in routine clinical practice. This convergence of outcomes suggests that the benefits observed with VRAYLAR may extend across the patient experience and likewise reinforce the importance of evaluating treatment success more broadly than symptom improvement alone.   Saurabh: The CReW BP-I study reported a substantial reduction in both MADRS and FAST scores over 12 weeks. How does the improvement in functioning alongside symptom reduction shape the understanding of treatment benefit in bipolar I depression?   Roger: MADRS and FAST assess distinct but clinically relevant domains – depressive symptom severity and functional impairment. Seeing significant changes in both measures in a prospective real-world study suggests that the treatment benefit observed in the CReW BP-I study was not limited to symptom reduction but was accompanied by improved functioning. This is clinically relevant in BP-I, where functional impairment can persist even as depressive symptoms improve. The alignment across these measures provides a broader assessment of treatment response and its potential relevance to patients’ everyday functioning.   Saurabh: The ProACt study found improvements in depressive symptoms as well as functioning, motivation, energy, and anhedonia with adjunctive VRAYLAR. What makes these broader measures particularly relevant when assessing treatment response in MDD?   Andrew: By the time a patient seeks treatment for depression, it is often because the condition is affecting their ability to function in important areas of their life – whether that’s at home, at work, or in their relationships.   The prospective design of ProACt allowed us to evaluate measures like FAST alongside depression symptoms to help us understand real-world patient experiences across different areas such as relationships, managing finances, household responsibilities, and autonomy. Looking at these broader measures alongside depressive symptoms gives us a more complete picture of treatment response, so that healthcare professionals can better understand patients’ needs and ultimately help them reengage in their daily lives.   Saurabh: Improvements in anhedonia and motivation and energy emerged as early as week two in the ProACt interim analysis. What could earlier changes in these domains mean for patients navigating the functional burden of depression?   Andrew: Anhedonia, low energy, and motivation can be particularly burdensome symptoms of depression because of their impact on day-to-day functioning, and with traditional antidepressants, it can take several weeks for these symptoms to get better. By the time many patients seek treatment, they’ve often been struggling with depression for a long time and may have already tried multiple medications before finding a regimen that works for them. That’s why achieving meaningful improvement as early as possible is so important, particularly for symptoms such as anhedonia, energy, and motivation, which can have significant impact on daily functioning and are often difficult to address with standard antidepressants.   Seeing improvements in these areas as early as week two is encouraging, as changes in these symptoms may translate into patients being better able to engage in everyday activities – whether that’s getting out of the house, returning to activities they enjoy, or managing daily responsibilities. Not all symptoms of depression are equally associated with functional impairment. That’s why looking at outcomes such as anhedonia, energy, and motivation alongside overall depressive symptoms can give us a more complete picture of how treatment may be affecting patients’ daily lives.   Saurabh: Real-world studies capture patient populations and treatment experiences that may differ from those represented in randomized clinical trials. How can real-world evidence complement clinical trial data in building a more complete picture of treatment effectiveness?   Julie: Randomized clinical trials are essential for establishing efficacy, but prospective real-world studies such as CReW BP-I and ProACt provide a valuable complementary perspective by following patients receiving treatment in routine clinical practice. Ultimately, patients are managing their depression in the context of their everyday lives – at home, at work, and in their relationships. Real-world evidence helps healthcare providers understand how a treatment performs in that setting and across broader, more clinically complex patient populations. Combined with randomized clinical trial data, real-world evidence gives us a more complete picture of treatment effectiveness.   Saurabh: Mood disorders are highly heterogeneous, with treatment response varying across patients. What role could real-world data play in advancing more individualized approaches to the treatment of MDD and bipolar I depression?   Julie: In MDD and BP-I, there is no single treatment response that defines success for every patient. Prospective real-world data can help us look beyond average treatment effects and better understand the range of responses clinicians may see in practice. Over time, these insights may help healthcare practitioners identify patterns in treatment response, supporting more informed and individualized treatment decisions.   Saurabh: With the latest VRAYLAR findings adding to the growing body of real-world evidence, what are the key areas where further research could deepen understanding of its role in managing depressive disorders?   Julie: Real-world evidence is needed to see how treatment works in patients’ day-to-day lives. Continued research across diverse patient populations can continue to complement randomized trial data and provide clinicians with a more complete picture of how VRAYLAR may fit into a patient’s care journey. Future research may further explore outcomes that matter most to patients. Depression impacts more than just how a patient feels. It can interfere with how they get through their day, how they succeed in school or at work, and how they relate to a partner or a child. These effects on a patient’s ability to function and the quality of their day-to-day experience are difficult to capture in clinical trials and are best understood through real-world evidence, deepening our understanding across a broad range of patients seen in routine clinical practice.   About Julie Adams, MD  Head, Precision Medicine Neuroscience, AbbVie  Julie Adams, MD is Head of Precision Medicine Neuroscience at AbbVie, where she focuses on advancing research in psychiatric and neurological disorders. Her work applies precision medicine approaches to better understand the biology underlying mental health conditions and support the development of more personalized treatments.  About Roger S. McIntyre, MD,   Professor of Psychiatry and Pharmacology at the University of Toronto and author of the CReW BP-I study   Roger S. McIntyre, MD is Professor of Psychiatry and Pharmacology at the University of Toronto and an internationally recognized expert in mood disorders. He has authored or co-authored more than 1,000 scientific articles and manuscripts and was named by Clarivate Analytics as one of “The World’s Most Influential Scientific Minds” from 2014 through 2023. His research focuses on the phenomenology, neurobiology, and treatment of mood disorders, with particular interest in innovative and rapid-acting therapies. Dr. McIntyre authored the CReW BP-I study evaluating VRAYLAR® (cariprazine) in patients with bipolar I depression in routine clinical practice. In 2023, he received the Colvin Prize for Outstanding Achievement in Mood Disorders Research from the Brain & Behavior Research Foundation. (Photo courtesy of the Depression and Bipolar Support Alliance)     About Andrew J. Cutler, MD,     Clinical Professor of Psychiatry at SUNY Upstate Medical University and author of the ProACt study  Andrew J. Cutler, MD is Chief Medical Officer at the Neuroscience Education Institute and Clinical Professor of Psychiatry at SUNY Upstate Medical University. A board-certified psychiatrist and Certified Physician Investigator, he has conducted clinical research since 1993 and served as a principal investigator on more than 400 clinical trials in a variety of CNS and medical indications, focusing on ADHD, bipolar disorder, depression and schizophrenia in children, adolescents and adults. Dr. Cutler authored the ProACt study evaluating adjunctive VRAYLAR® (cariprazine) in adults with major depressive disorder (MDD). He has authored more than 200 peer-reviewed scientific articles and is an experienced medical educator, having delivered hundreds of continuing medical education and Grand Rounds presentations. (Photo courtesy of the Neuroscience Education Institute)  The post Beyond Clinical Trials: AbbVie’s Julie Adams, Roger McIntyre, and Andrew Cutler on VRAYLAR’s Real-World Impact appeared first on PharmaShots.