Best Practices and Solutions in the New Inflammation Paradigm

Covance recently hosted a webinar “Best Practices and Solutions in the New Inflammation Paradigm,” where two Covance experts (Global Therapeutic Area Head for Inflammation Dr. Michael George and Executive Director of Operational Strategy and Planning Joan Meyer, Ph.D.) explored a profound shift in the perception and treatment of inflammation and its transformative impact on drug development and clinical trials.

Recent years have seen significant advances in the medical and scientific community’s knowledge of immunology and the pivotal role inflammation plays in disease, providing multiple new targets for anti-inflammatory therapy. A leading area of interest and activity, the global inflammatory therapeutics market is currently estimated at $55 billion per year and growing.

Traditionally, inflammatory diseases such as asthma, inflammatory bowel disease (IBD), and rheumatoid arthritis were addressed in a piecemeal fashion dictated by the physical site of the disease (e.g. lungs, gut, joints, etc.) However, recent discovery that seemingly unrelated diseases, like arthritis and IBD, can respond to the same biological therapies has led to the treatment of a newly conceived group of diseases called Immune-Mediated Inflammatory Disorders (IMIDs).

IMIDs – a true breakthrough in the way pathology is classified — represent more than 80 chronic autoimmune diseases many of which share some common inflammatory and molecular pathways. Diseases as varied as rheumatoid arthritis, multiple sclerosis, asthma, psoriasis, ulcerative colitis, and Crohn’s are among those classified as IMIDs. More than a name and classification, IMIDs represent a significant shift in the approach to the management of traditional inflammatory diseases from organ-based symptom relief to mechanism-based treatment.

For instance, certain biotherapeutic drugs designed to treat rheumatoid arthritis by modifying the immune response may also have therapeutic value in treating psoriasis and inflammatory bowel diseases because the diseases share some common pathways of immune signaling and cytokine dysregulation. Utilizing anti-cytokine as a strategy of targeted, active immunotherapy has been effective in treating multiple inflammatory conditions, confirming the IMID paradigm. Targeted biologic therapies have revolutionized treatment of IMIDs due to their efficacy, speed of onset, and tolerability.

This profound shift in how inflammation is perceived and treated has led to escalating client interest, increased R&D activity, and explosive investment in new mechanism-based targets and therapeutic approaches (novel small molecule, biologics, and biosimilar development, as well as biomarkers). While growth in the IMID biopharmaceutical pipeline is driving a wave of development opportunity across multiple areas simultaneously, biomarkers are also being leveraged to support rational expedited IMID drug development.

Currently, inflammation biomarkers are being used to 1) increase the ability to detect early therapeutic effects with a novel agents 2) allow expedited human proof of mechanism/concept studies to screen out and fast track promising drug candidates 3) identify patient subgroups that may benefit from more (or less) intensive immunosuppressive therapy or use of novel therapy and 4) predict subject response to treatment allowing closer monitoring of individuals judged to be most at risk of relapse.

Overall, the unlocking of this inflammation paradigm by scientists and the medical community has led to important research and market potential in a therapeutic area with significant unmet need. Furthermore, as the understanding of inflammation continues to evolve, there is an equal need for evolvement on the operational side of drug development through clinical trials to keep pace, including best practice approaches in optimizing and expediting clinical trial design.

The Operational Reality: Challenges and Best Practices

The shift from organ-based symptom relief to mechanism-based treatment of IMIDs has generated new challenges and opportunities to consider for conducting inflammation clinical trials, which have never been short of potential pitfalls.

Inflammation clinical trials are notorious for encountering factors that threaten to undermine the quality of the compound characterization and the ability to identify and understand vital safety and efficacy signals. Common pitfalls include large placebo response, issues around the use of Patient Reported Outcomes (PROs), study drug compliance, inter- and intra-rater variability, and patient retention given the long-term nature of inflammation studies.

However, while pitfalls common to inflammation studies abound, the potential re-applicability of therapies to different IMIDs in different categories allows for plenty of room to improve the conduct of clinical trials. Operationally approaching IMIDs as an interconnected area makes practical sense and makes it possible to leverage best practices and experience across diseases.

Some similarities inherent across inflammation studies include standard of care, patient reported outcomes, requirements for rater training, similar lab tests, increasing use of novel biomarkers, patients generally known to sites given chronic nature of disease, positive patient compliance, and a strong network of advocacy groups. Given these similarities, best practices learned can be applied across studies. In regard to inflammation studies, trial design and site training is crucial to minimize placebo response, plus a solid base of IMID study experience is needed for successful execution. Finally, an investigator knowledgebase is significant in most IMIDs.

The increased clinical trial activity for inflammation studies is also driving competition for patients, which makes it vital to have a deep view into site/patient competition and to identify the most appropriate sites for an inflammation study. Covance’s Clinical OptimizationTM methodology Xcellerate is helping many clients find and target high-performing sites for inflammation and other studies. A proprietary Covance database, Xcellerate provides access to over 132,000 physicians in a variety of disease areas, plus quality and recruitment metrics.

Overall, in order to systematically and effectively negotiate the impact on clinical development strategies and clinical trials, it is crucial to understand the overall paradigm shift. To learn more about this new inflammation paradigm and its impact on trial conduct, please visit http://bit.ly/U8mrx9.

About the Authors:

Michael George, MD, is Vice President and Global Therapeutic Head for Inflammation, Infectious Diseases, and General Medicine at Covance. Dr. George has more than 21 years of experience in the pharmaceutical industry, having held numerous roles of increasing leadership across all phases of clinical drug development in various therapeutic areas with both regional and global responsibility. Dr. George obtained his degrees from London University and completed his medical training at Westminster and Charing Cross Medical School before undertaking his postgraduate training in internal medicine and gaining membership of the royal college of physicians in the U.K. Dr. George’s publications include numerous articles in the areas of hypertension, heart failure, diabetic retinopathy, and neuro-endocrine modulation.

Joan Meyer, Ph.D., is the Operational Strategy & Planning Global Therapeutic Area Head for Inflammation, Infectious Diseases, and General Medicine at Covance. Dr. Meyer has more than 25 years of pharmaceutical and CRO experience, holding leadership positions in project management, strategic marketing, and study start-up. She has also served in leadership roles in the Ohio River Valley and National Arthritis Foundations. Dr. Meyer graduated from St. Mary’s University, Minnesota, with a BA in Biology and BA in Psychology. She received her Master of Science and Ph.D. in Neuroscience from the University of Illinois at Urbana-Champaign, where she taught in the College of Medicine.

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About Michael George, MD and Joan Meyer, Ph.D.

Dr. Joan Meyer is the Operational Strategy & Planning global therapeutic area head for Inflammation, Infectious Diseases and General Medicine, reporting in to the Covance office in Princeton, NJ. Dr. Meyer graduated from St. Mary’s University, Minnesota, with a BA in Biology and BA in Psychology. She received her Master of Science and PhD in Neuroscience from the University of Illinois at Urbana-Champaign. Dr. Meyer has more than 29 years of pharmaceutical and CRO experience, first joining Procter & Gamble, where she began her career in the research labs. While in the Clinical Development Division, Dr. Meyer led the development of drugs in the areas of arthritis, osteoporosis, gastrointestinal, urology, sleep and women’s health. Following Procter & Gamble, Dr. Meyer joined a global CRO with leadership positions in Project Management, Strategic Marketing and served as Global Head for Study Start Up.