Innovative outcome measures coupled with a focus on patient-centered clinical differentiation can help the biopharma industry make meaningful progress in the highly complex area of neuroscience.
Neurological diseases affect more than 3 billion people worldwide, a number that is expected to double over the next 20 years. Despite their prevalence, diseases of the brain and central nervous system remain especially difficult to diagnose, characterize and treat. As a result, roughly 9 out of every 10 neurology clinical trials test drug candidates that fail to achieve regulatory approval.
As CEO of Neurvati Neurosciences, my focus is on optimizing the scientific and clinical potential of neuroscience programs to improve their probability of success. I believe progress in neuroscience depends on multidimensional thinking—connecting the right biology, patient populations and clinical endpoints to generate data that reflect improvements meaningful to patients.
Building Momentum Toward Precision Neuroscience
Developing neuroscience therapies has long been challenging due to the complexity of the brain and the difficulty of studying it in living patients. Symptoms such as developmental delay, intellectual disabilities or behavior problems can appear across several different neurological disease states and are often difficult to quantify.
However, over the past several years, the neuroscience community has begun to see meaningful progress in regulatory recognition of biomarkers that reflect underlying disease biology. Recent FDA decisions—such as accelerated approvals based on amyloid PET reduction in Alzheimer’s disease, plasma neurofilament light chain (NfL) decreases in SOD1-ALS and tissue protein restoration in Duchenne muscular dystrophy—demonstrate growing comfort with surrogate endpoints that are reasonably likely to predict clinical benefit. In parallel, programs in neuronopathic lysosomal diseases, including those leveraging CSF substrate reduction as a mechanistically grounded biomarker, signal that regulators are increasingly willing to engage with sophisticated tools capable of quantifying CNS pathology directly.
Moreover, advances in genetic testing, multi-omic technologies and the development of plasma and CSF biomarkers are continuing to enhance our ability to select more enriched patient populations for clinical research. For example, measuring a-synuclein levels within the blood has been a useful diagnostic tool in Parkinson’s disease (PD) and can even help differentiate between PD subtypes. Concurrently, technologies including quantitative EEGs, evoked potentials and functional imaging (PET, fMRI) are setting new standards in measuring brain activity.
These developments underscore a positive shift: neuroscience is steadily building the evidentiary foundation needed to support precision therapies targeted to specific molecular and cellular mechanisms and moving closer to a future where disease-specific therapies can deliver outsized benefit compared to today’s largely symptomatic approaches.
Yet, while this momentum is encouraging, continued discipline is required to ensure that biomarkers—particularly CSF substrates and other quantitative measures—do more than demonstrate pharmacologic activity. The field must show that changes in these markers translate into outcomes that matter to patients and caregivers. For instance, several phosphorylated versions of Tau (pTau) have shown promise as plasma biomarkers for Alzheimer’s disease, yet the degree to which each pTau correlates to cognitive impairment varies greatly and is still being actively assessed.
Establishing these connections will require rigorous natural history modeling, thoughtful endpoint selection and trials that incorporate meaningful patient-centered measures alongside biomarker readouts. This will ensure that our progress is purposeful: each step forward should tighten the link between biological effect and real-world clinical value.
A New Mindset
As we develop innovative strategies to improve clinical trial design for neurological diseases, we should re-evaluate how we define therapeutic success. Transformative treatments that halt or reverse symptoms remain the ultimate goal. Yet to get there, we must recognize the value of therapies capable of targeting underlying disease biology that provide measurable and clinically meaningful impacts for patients, including tangible enhancements in neurological function, neuropsychiatric symptoms and activities of daily living.
By designing trials that capture patient-centered outcomes, researchers can identify therapies that provide true clinical value, even if they do not completely reverse disease. The key is not to celebrate incremental gains in isolation, but to pursue measurable differentiation that patients, clinicians and caregivers can feel in daily life.
To further boost the success rate of neuroscience trials, we must routinely mine completed research for every available insight that can guide future work, either within the same disease or across similar mechanisms. These insights can reveal where differentiation already exists and how it might be amplified in subsequent studies. The goal is not to pursue every candidate that falls short in late-stage research but to think beyond a binary notion of success or failure.
Given the continued improvements in our understanding of brain biology and function, combined with advances in monitoring and clinical assessment technologies, opportunities to design trials around meaningful patient-centered outcomes will continue to grow. Quantitative biomarkers, digital endpoints and functional measures are expanding what can be measured—and improved—for patients living with neurological disease.
Neuroscience has reached an inflection point that enables sponsors to pursue and demonstrate patient-centered differentiation. We can now design better clinical trials that are defined by well-characterized patient populations, precise mechanistic insights, and innovative measurement tools. Industry leaders must build the expertise to recognize when clinical data indicate a therapy’s potential to deliver improved outcomes. With this mindset, neurological drug development can move beyond small steps toward meaningful leaps.
