CNS Clinical Trials: How to Navigate Challenges to Success

According to the National Institute of Mental Health, a quarter of the United States population have at least one Central Nervous System (CNS) disease- and this statistic only seems to be on the rise. According to the World Health Organization, nearly one in six of the world’s population suffer from CNS neurological disorders such as Alzheimer's, Multiple Sclerosis, Epilepsy, and more. While CNS diseases can consist of more than 600 conditions, and although many are well known, there are also many rare CNS disorders that affect a smaller number of patients who have access to few, if any, effective treatments.

With such staggering disease statistics and a clear need for effective treatments, why then do CNS-focused preclinical and clinical trials face such an uphill battle when it comes to bringing a new therapeutic to market?

The Challenges of CNS Clinical Trials

As reported in the article “The Need for New Approaches in CNS Drug Discovery: Why Drugs Have Failed, and What Can Be Done to Improve Outcomes” by Valentin K. Gribkoff, PhD and Leonard K. Kaczmarek, PhD, CNS drugs tend to have higher failure rates than non-CNS drugs, in both preclinical and clinical trials. There are a number of contributing factors, especially the fact that it is simply much more difficult to generate findings in CNS disease that can be translated into a successful clinical candidate than in most other therapeutic areas.

They go on to say, “the failure rate for new drugs targeting important central nervous system (CNS) diseases is very high relative to most other areas of drug discovery . . . This is most apparent in the case of drugs that attempt to alter the course of the disease or condition (disease-modifying drugs), and is particularly acute in the area of neurodegenerative diseases (NDDs). In many cases, the drugs that have had demonstrable effects are palliative treatments that have modest effects on disease symptoms and no demonstrable effect on disease progression.”

So, why do so many CNS drug trials fail? Issues include:

1. The difficulty to produce findings in CNS disease that can be translated into a successful clinical candidate.
2. Unexpected metabolic differences (pharmacokinetic (PK) profile) in drug candidate(s)
3. Challenges with predicated and emergent toxicity. When it comes to areas such as oncology, the levels of acceptable risk are greater for diseases where if left untreated the outcome is especially grim and/or fatal. Whereas, CNS conditions more often determine our personality or control our behavior, meaning that any potential side-effects that cause significant issues to our neurological and/or behavioral systems are often not worth the risk to potential patients.
4. Lack of animal models that have predictive validity — perhaps the most frequently referenced reason for the failure of CNS drugs in the clinic.
5. Both development and post-development regulatory reviews are longer and more laborious than other industry drugs.

Not every issue is unique to CNS alone, but together it is clear that CNS trials tend to have a harder time reaching success.

How to Find Success with Your CNS Trial

One of the best things you can do to help ensure the success of your CNS-related clinical or preclinical trial, is to partner with an industry expert who can help guide the way forward. Central laboratories working in the CNS space should look for dedicated, highly experienced testing partners who are familiar with the challenges that CNS studies can face.

The example of Alzheimer’s Disease trials shows how by finding an experienced partner in CNS-specific studies, you greatly enhance your study’s ability to be successful — and along with it the success of a potential life-changing CNS therapy for patients in need.

“For patients with Alzheimer’s disease, the medications we currently have to offer are very ineffective and we desperately need better treatments both to improve current symptoms of memory loss and to slow down the disease process,” said David Gill, MD, Director of the Memory Center at Rochester Regional Health. “The only way to find new medications is through research studies."

ACM is By Your Side, Every Step of the Study

At ACM Global Laboratories, we are proud to have extensive experience with both preclinical and clinical CNS trials. In the past five years alone, we have conducted more than 100 CNS-related studies.

Our scientific and analytical experts work as an extension of your team to understand the specific testing requirements and intricacies of your CNS study. We'll help you plan the optimal study and test menu design, anticipate your needs and respond quickly to your requests. This approach provides complete transparency throughout the process, so you are assured of the relevance, accuracy and timeliness of your testing data.

Offering a full range of central laboratory services, we use the most up-to-date and appropriate testing option to ensure we deliver the assay endpoints your CNS study requires.

Clinical Trials Management: Selecting a Central Lab to Support the Clinical Trial Process

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To receive a free consultation from our experts on how we can help you run your next CNS study, contact us.

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