Does Biopharma Drug Discovery Need to Evolve to Include Objective, Longitudinal, Broad-Spectrum Real-World Data?

It is well established that drugs for psychiatric conditions suffer some of the lowest approval rates when compared to other major therapeutic areas. There are many underlying factors, including complex and poorly understood etiology which are heterogeneous in presentation and presumably underlying pathophysiology.

Additionally, traditional clinical studies fail to objectively assess cognitive function as part of patient eligibility criteria or stratify patients according to the presence or degree of cognitive impairment.

Cognitive function assessments and electroencephalography (EEG) enable measurement of pharmacodynamic endpoints in early-stage, translational psychiatric studies. However, many studies do not leverage these invaluable tools today. Visual evoked potential and auditory evoked potential (electrical signals generated by the brain in response to visual and auditory stimuli, respectively) are well established and validated in animal models and can be translated in humans.

Digital biomarkers — including EEG — have the potential to help enrich patient populations in clinical studies, help us better understand drug target engagement and enable better decision-making in clinical trials.

In this Xtalks Spotlight edition, Xtalks spoke with Dr. Snezana Milanovic, Senior Director of Translational Medicine and Early Development at Sumitomo Pharma America, about how EEG-derived digital biomarkers can help advance clinical research.

Dr. Milanovic discusses the challenges clinicians encounter in diagnosing and treating neuropsychiatric disorders in their daily practice. Additionally, she examines the limitations of prevalent paper-based assessments in current clinical practice and research, providing insight into the cascading impact of these challenges on the broader clinical research landscape.

Dr. Milanovic is a psychiatrist, specializing in drug development for psychosis and mood disorders, with a keen interest in using neuroplasticity-based biomarker tools such as EEG and cognitive tasks.

The views expressed by Dr. Milanovic during this interview are hers individually and do not necessarily reflect the views of Sumitomo Pharma America.

RELATED ON-DEMAND XTALKS WEBINAR: Case Study: EEG Digital Biomarkers in Neuropsychiatric Clinical Studies

Register for this free webinar to learn how digital biomarkers have the potential to transform neuropsychiatry, enabling personalized treatment. The featured speakers will discuss how electroencephalography (EEG)-derived digital biomarkers of functional, cognitive neurophysiology can generate scalable real-world data in neuropsychiatric clinical studies from translation to market.

Challenges in Clinical Research for Neuropsychiatric Disorders

Dr. Milanovic highlighted one of the main challenges in clinical research for neuropsychiatric disorders: getting an accurate diagnosis for patients. The current reliance on global assessments has limitations due to the overlapping range of symptoms in neuropsychiatric disorders which can confound diagnoses. This mirrors what happens in everyday clinical practice, where patients often receive multiple medications before finding an effective treatment.

In the context of clinical trials, this challenge is further complicated, requiring a nuanced approach to ensure appropriate patient stratification. Also, the timing of patient presentation and the consideration of ongoing stressors add layers of complexity to clinical research.

The dynamic nature of neuropsychiatric conditions also demands a thorough understanding of the time course of the disease, response to medications and comorbid symptoms. Challenges such as baseline medications and limited access to outpatient medical records further complicate the picture.

“There is a need to move beyond the scales and try to identify reliable trait biomarkers that would give us clues about the biological footprint of a disorder, and also disease state biomarkers, which would help us understand the course of illness and possible fluctuations and help us design better drugs.”

— Dr. Milanovic

Another significant hurdle in psychiatric clinical studies involves the intricate interaction between patients and their treating clinicians. The placebo effect, influenced by an alliance between subjects and clinicians, can confound the accuracy of reported symptoms. For instance, Dr. Milanovic underlines the common occurrence of patients underreporting or overreporting their symptoms.

Additionally, paper-based clinical assessments have been a cornerstone in evaluating patients in clinical practice. However, their subjective nature poses challenges, and Dr. Milanovic emphasizes their limitations of providing objective physiological data crucial for a comprehensive understanding of patients’ conditions.

A shift towards biomarker-driven approaches may refine clinical trial design and could lay the foundation for the development of more effective and targeted drugs.

Advancing Neuropsychiatric Clinical Research with EEG-Derived Digital Biomarkers

Dr. Milanovic highlights the need for more objective biomarkers in neuropsychiatric clinical research, specifically mentioning EEG as a potential game-changer if proven reliable. EEG provides a direct and non-invasive measurement of the central nervous system response, offering a potential solution to the subjectivity inherent in traditional assessments.

Key points supporting the incorporation of EEG-derived digital biomarkers include:

• Subjectivity of paper-based assessments: Traditional clinical assessments relying on paper documentation lack the objectivity needed for accurate evaluations. EEG, by directly measuring neurological responses, bridges this gap.
• Placebo response in clinical studies: Paper-based assessments are known to introduce the potential for a placebo response, particularly in mood and anxiety disorders. EEG can objectively counteract this phenomenon.
• Overcoming the historical challenges of EEG: It is important to acknowledge the historical challenges associated with EEG, including cost and variable results. However, recent advancements and promising biomarkers, such as the mismatch negativity response in schizophrenia, make EEG a compelling avenue for exploration in neuropsychiatric drug development.
• Effectiveness in drug response prediction: Despite initial hurdles, some studies have suggested that EEG can aid in detecting and predicting drug responses. This suggests that EEG-derived digital biomarkers have the potential to revolutionize the way we approach psychiatric assessments and drug development.

Dr. Milanovic draws a parallel with oncology, emphasizing the importance of comprehensive digital platforms in psychiatry to enable better decision-making in clinical trials and, ultimately, clinical practice.

Sumitomo Pharma America’s Collaboration with Cumulus Neuroscience

The capability to assess neuroplasticity holds significance in numerous neuropsychiatric conditions, frequently indicating a patient’s potential for improvement. However, standard paradigms for measuring neuroplasticity in the clinic can take 60 – 90 minutes, making it difficult to include in clinical studies.

Sumitomo Pharma America recently engaged Cumulus Neuroscience on a Phase I clinical study focused on neuroplasticity and a poster featuring key findings was presented at the European College of Neuropsychopharmacology meeting in October 2023. The study aimed to explore the feasibility of deploying a low-burden dry-sensor EEG headset to measure and validate a shortened 10 – 15 minute VEP-LTP paradigm.

Dr. Milanovic’s insights reveal that the study successfully detected clear modulation effects in a modest number of sessions and a small number of subjects. This efficiency aligns with the scale required in early-stage clinical studies. It shows that the Cumulus Neuroassessment Platform could prove practical in early decision-making on compounds targeting neuroplasticity.

The Need for Objective, Longitudinal, Broad Spectrum, Real-World Data

Dr. Milanovic’s insights underscore the critical need for innovation in psychiatric drug discovery. Bringing the conversation full circle, Dr. Milanovic asserts the necessity for biopharma drug discovery to evolve by including objective longitudinal, broad-spectrum, real-world data.

Reflecting on the stagnation in psychiatric drug development over the past few decades, she envisions EEG as a digital biomarker and a transformative additional approach to collecting data that defines the heterogeneity of psychiatric patients.

Dr. Milanovic underscores the potential of visual-evoked potentials and auditory-evoked potentials, well-established and validated in animal models, as key components in this transformation. The goal is to translate these findings into humans, integrating EEG signals into digital biomarkers. The aim of such tools is to help enrich patient populations and better understand compounds to enable better decision-making in clinical trials.

For more insights into the use of digital biomarkers in neuropsychiatric clinical research, be sure to watch the Spotlight feature with Dr. Milanovic. In addition, register for the on-demand webinar Case Study: EEG Digital Biomarkers in Neuropsychiatric Clinical Studies sponsored by Cumulus Neuroscience.

This article was created in collaboration with the sponsoring company and the Xtalks editorial team.