Top 4 Trends For Neuropsychiatric Disease Research In 2025
By Kelly Abernathy, VP of clinical development, Arrivo BioVentures, and Joel Raskin, MD, chief medical advisor, Arrivo BioVentures
After years of lagging investment and innovation in neuropsychiatric diseases, we are now seeing a resurgence in research. Driving the renewed interest in neuropsychiatric diseases is the continued high unmet medical need, the push toward personalized medicine, and the discovery of novel mechanisms of action and biomarkers, which are all leading to improved technologies to evaluate targets at earlier stages of development. These trends will influence the future of clinical trials in 2025 and beyond.
1. New Mechanisms Of Action Are All The Rage
New mechanisms of action (MOAs) that are further upstream are being studied and are reparative, instead of focused on symptom improvement. Historically, many treatments, in particular for psychiatric diseases, have been receptor-based, targeting increases in serotonin, dopamine, etc. We are now seeing new medications that, for example, impact gene expression and cellular stability. At Arrivo, we have a SIRT6 activator in development for major depressive disorder (MDD) in women, as well as other indications in both sexes. SIRT6 is an enzyme that is epigenetic in nature and involved in DNA repair, mitochondrial health, inflammation control, and lipid and glucose metabolism. It works upstream, silencing gene pathways that are at the root of the diseases we are trying to target. SIRT6 is like a multitalented conductor, ensuring the orchestra of our metabolic processes plays in harmony.
GLP-1 agonists are another excellent example of new MOAs that are having broad effects because they are getting at the fundamental causes of disease. Recent literature suggests that these drugs are having profound impacts on metabolic diseases, cardiovascular diseases, and potentially even CNS diseases.
For new products with further upstream/reparative MOAs, we will likely see more studies designed to evaluate maintenance of effect post-treatment and to assess improvement in comorbid conditions beyond the primary indication being evaluated. For example, at Arrivo, we are including efficacy assessments during a post-treatment follow-up period to evaluate the maintenance of effect and/or continued improvement for our SIRT6 activator, given its epigenetic MOA. We are also evaluating improvement in cognitive, inflammatory, and metabolic disease parameters in study participants with depression.
2. The Age Of AI Continues
Advancements in technology, including AI, are allowing for a better understanding of potential drug candidates earlier in the discovery and development process. Biomarkers and evidence of target engagement are essential in studying disorders where, in the past, we relied only on subjective rating scales. From drug discovery and design where AI is speeding the creation of novel structures to the ability to compare the profile of a drug candidate across a variety of parameters and databases of both human subjects with disease and normal volunteers, the amount of information available to drug developers earlier in the process will allow for more efficient and potentially faster development. As an example, Arrivo is using AI combined with qEEG technology to better understand target engagement, BNA™ (Brain Network Analytics), and dose response of our SIRT6 activator in a Phase 1 exploratory study. AI is comparing the activity of our drug in different brain regions, both to baseline activity and to databases of patients with a wide range of neuropsychiatric diseases as well as healthy control subjects. This can help us understand where our drug is working and what other potential diseases we can target. These kinds of analyses may also help to identify the therapeutic range more efficiently for dosing, potentially avoiding the need for large dose-ranging studies.
3. Subpopulation Studies Get The Spotlight
Studying subpopulations in disease areas is becoming increasingly common and important. Personalized medicine continues to be a goal for the biopharma industry. The combination of MOAs, a better understanding of disease pathophysiology, and improved technology is aiding the identification of subpopulations that best respond to specific drug candidates. One of our drug candidates SP-624 appears to silence genes that are preferentially important to women with depression. Following the results of our first Phase 2 study, and in consultation with the FDA, we are now conducting a Phase 2b/3 study with efficacy in women as the primary endpoint.
More research and development work will be conducted in diseases and health conditions that are exclusive to or that predominantly occur in women. Women represent approximately 50% of the U.S. and world population and have some of the most debilitating neuropsychiatric and neurodegenerative diseases such as MDD and Alzheimer’s disease. These conditions are twice as common in women than men, and yet there has long been a critical knowledge gap in understanding female-specific physiology and pharmacology. Recent research has shown important sex-specific differences in the origin of many diseases as well as disease symptomatology and outcomes. Plus, there has been a growing public demand for more research in women’s health. Animal models historically conducted exclusively in male animals are starting to be conducted with female and male animals and include sex-specific data analyses. These preclinical studies will ultimately better inform human trials and facilitate the development of innovative therapeutics specific to women. We are starting to see that the root cause of some disease processes may be different in women versus men; therefore, treatments and interventions, particularly those that target the root cause of the disease, are likely to be different between the sexes.
4. More Objective Measures Of Disease Progression
In neuropsychiatry, there is a trend toward including more objective measures of disease progression or improvement in addition to, or instead of, subjective investigator-rated scales administered at weekly visits. Digital technologies, real-time assessments, and biomarkers will all be more reliable than traditional office visits. For example, we are using CANTAB® assessments that provide scientifically validated, highly sensitive, precise, and objective measures of cognitive function, correlated to neural networks.
Investments in resources to expand research for neuropsychiatric disorders, aided by technology and objective measures, opens the door to new treatments with novel MOAs that have better efficacy and tolerability. It allows the companies developing new treatments in this therapeutic area to also examine subpopulations of patients that are more likely to be diagnosed with a particular disorder and more likely to have a good therapeutic outcome. As the biopharma industry moves towards personalized medicine approaches to drug development, progress will lead to improved treatments for patients and their physicians in diseases where currently better options are needed.
About The Authors:
Kelly Abernathy has over 25 years of experience managing Phase 1-4 clinical development programs in both adult and adolescent populations, with the majority of those programs involving products for the treatment of CNS diseases and disorders. Prior to joining Arrivo, Kelly was the director of clinical affairs at Aerial BioPharma, a successful drug development company that sold its lead product for excessive daytime sleepiness in narcolepsy to Jazz Pharmaceuticals in 2014. Kelly graduated magna cum laude with a BS in biology, minoring in chemistry from Meredith College in Raleigh, NC.
Joel Raskin, MD brings almost 40 years of clinical, academic, and pharmaceutical research and medical affairs experience to his role as chief medical advisor to Arrivo. Joel was a community and academic psychiatrist, consultant to public and private industry, and the head of the depression clinic and clinical trials specialist mood disorders at the Center for Addiction and Mental Health, University of Toronto before joining Eli Lilly in 1999. During his 20 years at Eli Lilly, Joel held various global team roles in neuroscience drug development and commercialization, working in mood and anxiety disorders, schizophrenia, chronic pain, Alzheimer’s, and migraine. He has published nearly 100 articles and has presented at international conferences and academic institutions. Joel continues to consult in drug development and mentors researchers at the University of Toronto Health Innovation Hub.