On July 22, 2021, the Food and Drug Administration (FDA) hosted the Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics VI (GREAT VI) Workshop on Celiac Disease – the second workshop ever held by the FDA for celiac disease.

The goal of this workshop was for the FDA to better understand the role of measuring symptoms and intestinal healing in celiac disease as new therapeutics advance through the drug development pipeline.

A digital representation of intestines, highlighting the affects of what a biopsy can uncover.

The workshop served as a public forum for discussion and collaboration between the FDA, drug developers, researchers, clinicians, and patients to help guide how to measure efficacy for therapeutics for celiac disease.

Three main topics were discussed:

  • The role of monitoring intestinal healing to determine whether a treatment is effective.
  • Considerations for developing drugs for pediatric patients.
  • The role of gluten challenges in clinical trials.

Session 1: How do we determine if treatments are effective and beneficial to patients with celiac disease?

The first session of the workshop focused on the benefits and limitations of using biopsy to measure intestinal healing in celiac disease, as ongoing intestinal damage has been linked to long-term health complications, including heart disease and cancer.

Benjamin Lebwohl, MD, Director of Clinical Research at the Celiac Disease Center at Columbia University and CDF Young Investigator Grantee, began by explaining that symptoms and blood tests are not enough to prove intestinal healing, and suggested that routine biopsies be incorporated into follow-up care to measure intestinal healing.

Jocelyn Silvester, MD, PhD, Pediatric Gastroenterologist at Boston Children’s Hospital, Harvard Medical School Pediatric Instructor, and CDF Young Investigator Award Grantee, presented special considerations for pediatric biopsies, such as the increased risk posed by sedation in children versus adults.

Marie Robert, MD, Professor of Pathology and Medicine (Digestive Diseases) at Yale University School of Medicine, explained that it is important for clinical trials to collect data in a variety of ways, including both biopsies and reports from patients about how they feel, to maximize understanding of the disease.

In the following Q&A session, when CDF Advocacy Ambassador Kelsey Smith was asked if she would be willing to take a drug that made her feel better, with no effect on her intestinal healing, she responded, “Yes, absolutely…from a patient perspective, celiac disease impacts our lives in a major way, and we need something that will allow us to continue going day to day, even if we’re on a gluten-free diet.”

Session 2: What is the framework for pediatric drug development in celiac disease?

The second session of the workshop discussed pediatric celiac disease and drug development.

Mona Khurana, MD, FDA Medical Officer, explained that the results of an adult study can sometimes be used to predict how a treatment will work in children, which can make pediatric treatments available more quickly.

Maureen Leonard, MD, Clinical Director of the Center for Celiac Research and Treatment at Mass General Hospital for Children, outlined some of the less obvious signs of celiac disease in children, such as dental enamel defects, and discussed the need for a multi-disciplinary team including a dietitian, social worker, psychologist, and psychiatrist to manage the disease throughout childhood.

Christopher St. Clair, PharmD, FDA Clinical Outcome Assessment Reviewer, explained that both quantitative evidence (such as changes in how often patients experience symptoms) and qualitative evidence (such as patients describing their experiences in an interview) are needed to determine if a treatment creates meaningful change.

Tyler Friedman, 17-year-old high school student with celiac disease, spoke about the social impact of the disease and the life-changing potential of a drug for symptom relief, expressing “the power that celiac has over [his] decisions would shrink exponentially.”

CDF Patient Advocates Beckett Hardin and his mother Kathy Hardin echoed the need for symptom relief by explaining that, while a drug to heal the intestine is the ultimate goal, celiac patients would greatly benefit from a drug that could relieve symptoms in the meantime alongside their gluten-free diet, as long as the drug itself does not cause further intestinal damage.

Session 3: What is the role of gluten challenges in clinical trials?

The third and final session of the workshop focused on the role of gluten challenges in clinical trials.

Joseph Murray, MD, Gastroenterologist at the Mayo Clinic and CDF Medical Advisory Board Member, described the intestinal damage caused by accidental gluten exposure in day-to-day life and recommended that routine biopsies be used for adults with ongoing symptoms to check whether they are being exposed to gluten unknowingly.

Jason Tye-Din, MBBS, PhD, head of the Coeliac Disease Research Lab at Walter and Eliza Hall Institute and Gastroenterologist at the Royal Melbourne Hospital, discussed how intestinal damage caused by gluten depends on the amount of gluten and the length of gluten exposure, emphasizing the need for a more standardized approach to gluten challenges in clinical trials.

Daniel Leffler, MD, MS, Medical Director of Takeda Pharmaceuticals, Director of Clinical Research at the Celiac Center at Beth Israel Deaconess Medical Center, and CDF Medical Advisory Board Member, stressed the importance of gluten challenges in clinical trials and explained that monitored gluten exposure is generally safe and does not cause long-term damage.

When asked for a patient’s perspective on gluten challenges, CDF Patient Advocate Kelsey Smith spoke about the need for more patient education from medical professionals experienced with celiac disease, explaining that “patients would be more willing to participate in [gluten challenges] if they had more education from the very beginning.”

This second GREAT workshop on celiac disease succeeded in shining a light on patient experiences and identifying where current knowledge gaps exist in celiac disease research. The discussion highlighted the urgent need for a drug that reduces symptoms to alleviate patient suffering, as well as the long-term goal of developing a drug that promotes intestinal healing.

Join the Celiac Disease Foundation today in continuing to amplify patient voices by becoming a patient advocate, and consider participating in research to help develop better treatments and, one day, a cure for celiac disease.

Another GREAT Day for Celiac Disease – 2021 FDA Workshop