Guest Column | September 11, 2023

An Easier Way To Meet The Needs Of Modern Clinical Trials

By Dr. Fred Grossman, Chief Medical Officer at Coya Therapeutics

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Over the decades since the modern clinical trial was developed, the clinical trial process has evolved, leading to steadily improved results across the industry. However, despite those improvements, 90% of drug candidates still fail clinical trials. For example, in Alzheimer's disease, one of the most prevalent neurodegenerative diseases and the most common type of dementia, the success rate for clinical trials plunges from 10% to 2%.

In fact, it still takes 10 to 15 years and over $1 billion for a traditionally developed drug candidate to make it all the way from the development stage onto the market. These statistics show why it's such an uphill battle for biotechnology companies to go it alone. They also demonstrate the importance of clinical trial design.

Thoughtful trial design, precision, and efficacy are all key factors during the development and commercialization phases. Other critical considerations include unlocking the value of potential drugs by placing real-world, patient-centered treatment at the heart of the clinical trial process. These and other factors all play crucial roles in clinical trial design.

A Distinctive Approach to Clinical Trials

Coya Therapeutics has adopted a distinctive approach that combines trial design with collaborative partnerships to drive advancements in clinical technologies. This clinical stage company focuses on therapies for unmet medical needs in neurodegenerative, autoimmune, and metabolic diseases that target regulatory T cells, also known as Tregs.

Coya is focused on neurodegenerative diseases, especially ALS and Alzheimer's disease. This focus on neurodegenerative diseases highlights the importance of patient-centered care because such diseases have relatively small treatment effects and are composed of a heterogeneous population.

As a result, knowing exactly which patient population or subtype is to be studied is critical. For example, some treatments might selectively target certain subtypes of ALS based on preclinical data and unmet needs, such as the ALS-sporadic type, which is more prevalent than the familial subtype. Other ALS treatments might zero in on specific molecular or symptom clusters.

On the other hand, some treatments are more appropriate for a broad cross-section of patients because they're capable of treating a wider population. Thus, effective clinical trials feature a patient-centered design that requires selecting a target population based on the treatment's mechanism of action and unmet medical needs.

For ALS, which is a heterogeneous disease, if a potential treatment is likely to be efficacious for all subtypes, it's critical to ensure that subclassifications are stratified and balanced across treatment and placebo groups to allow for a complete comparative analysis. Appropriate statistical powering, which is the probability of detecting a difference between study groups when a true difference exists, is also critical for companies (and regulatory agencies such as the FDA) to be confident in the results. Much is riding on having accurate outcomes, which means either advancing or discontinuing a program.

Achieving Objective Efficacy in Trial Design

Additionally, biomarkers are critical as an objective measure of efficacy because the efficacy scales often used in clinical trials rely on subject and investigator assessments and are subjective and subject to rater and expectation biases. As a result, biomarkers should be explored as early as possible during the development of a potential treatment.

Of course, reducing placebo responses is essential but challenging, and it requires careful clinical trial design. For example, having too many treatment arms (versus placebo) can create an expectation of a clinical effect on the part of subjects, which might bias the results. Such a scenario gives subjects a greater expectation of being in the treatment group rather than on a placebo.

Also critical for clinical trial design is blinding of raters and staff so that they do not know the treatment or placebo assignments. Giving raters and other staff members the appropriate training is essential, as is using trial sites with experience in the type of therapies your company is working on. Trial sites should also have a solid track record of enrollment and consistency to help iron out any potential efficacy-related problems. Some trial designs use external centralized raters (who are not at the research site) for consistency and to avoid rater bias.

It's also a good idea to continue evaluating blinded outlying data on an ongoing basis. For example, if every patient's pulse or blood pressure is exactly the same week after week, it suggests staff members aren't paying attention or are recording data incorrectly. While there are many ways to assess consistency, sponsors should be fully engaged rather than distant, assuming that everything is being done correctly using best practices.

Clinical trial sponsors may also consider using more complex, adaptive designs to create flexibility and efficiencies like testing several dosages. In fact, sometimes being part of a large consortium in the process of testing several different treatments can be a good strategy, especially if the clinical trials are managed by reputable academic centers.

Call for Collaboration Versus M&A

Unfortunately, worries about protecting proprietary information may cause some companies to prefer mergers and acquisitions over strategic collaborations between companies, experts, and organizations. However, strategic collaborations may be just what the industry needs to boost success rates and reduce the size of the investments needed to bring new drugs to the market.

On the other hand, M&A offers more permanent combinations. In fact, M&A has long been a crucial part of the biotechnology industry. Pharmaceutical giants with the needed funds to make their innovations go much further have snatched up many promising up-and-comers over the years.

As a result, many more patients end up benefiting from groundbreaking science that dramatically improves their quality of life. For these reasons, it should come as no surprise that a survey conducted by KPMG found that 60% of healthcare and life sciences investors expect to see increased M&A activity among biopharma companies in 2023.

However, biotech companies shouldn't restrict themselves purely to M&A because strategic collaborations like the consortium example given above can deliver even greater results — for companies and patients alike.

How to Forge Partnerships That Really Work

When it comes to strategic collaborations, not just any partner will do. It's critical that biotech companies align themselves with the key thought leaders who are defining their space. These academic and industry partnerships are quite beneficial for companies. They ensure that the latest data, technology, and science are shared, enabling the partner companies to optimize their trial designs and enhance innovation by challenging conventional thinking.

Coya Therapeutics has enjoyed significant success through the partnerships it has struck. The company has drawn together a very prominent scientific advisory board that includes several world-renown experts. For example, Dr. Simon Sakaguchi of the National Academy of Sciences, who is credited with the original discovery of Tregs in 1995, is one member of the advisory board.

Other members include Dr. Stan Appel, who holds the Distinguished Chair in ALS Research and serves as co-director of the Houston Methodist Neurological Institute. Dr. Lawrence Steinman of the National Academy of Medicine, also a genetics professor at Stanford University, and Dr. Malcolm Brenner, director of the Center for Cell and Gene Therapy and a Baylor College professor, also serve on Coya's scientific advisory board. Finally, Dr. Clive Svendsen, director of the Cedar Sinai Regenerative Medicine Institute is also a member of the board.

Over the years, Coya Therapeutics has found these partnerships and collaborations with other companies to be highly beneficial. They allow the company to take full advantage of shared knowledge and operational, scientific, and analytic methodologies and overall synergies.

Achieving Efficiency

Coya's clinical trial strategy is also anchored in efficiency, which can also be achieved through strategic collaborations.

According to Arun Swaminathan, Ph.D., chief business officer for Coya, designing scientifically strong proof-of-concept studies that assess biomarkers, efficacy, and safety in a time-efficient manner based on those insights is a hallmark of their trial-design process. Next, they move forward with larger trials.

“In the case of a high-unmet-need disease like ALS, a combination of regulatory precedence and our POC data allows us to move rapidly to potentially registrational trials in a time and cost-effective manner with the objective of bringing potential new options to patients faster,” adds Swaminathan.

Taking Cues from Other Clinical Trials

Finally, in designing its clinical trials, Coya Therapeutics takes some pages out of the playbook commonly used to plan trials for cancer treatments. The company's strategy involves several steps commonly used in cancer trials, starting with identifying viable and predictive blood biomarkers that can stratify patients or monitor their clinical responses.

Next, Coya runs small POC trials that provide preliminary evidence of the treatment's safety and efficacy. Finally, the company moves onto larger trials that incorporate those earlier findings from its previous POC trials on its Treg-based therapies for neurodegenerative diseases.

“To date, this has proven highly successful for our ALS and Alzheimer's programs, and we are moving quickly into larger validating trials,” says Coya Therapeutics CEO Howard Berman, Ph.D.

About the Author

Dr. Fred Grossman serves as chief medical officer of Coya Therapeutics. He has over 20 years of drug-development expertise, acquired through multiple senior executive leadership positions at both large and small pharmaceutical companies leading the development and FDA approval of numerous multi-billion-dollar blockbuster drugs targeting significant unmet deeds.