We’ve come a long way, baby.

In the plenary talk on the first day, Marie Egan, M.D., provided an important overview of how far CF research has come over the past 30 years in her talk, “Emerging Technologies for CFTR Restoration in All People with CF”. This talk highlighted innovative technologies, including RNA therapies, gene therapies, and gene editing technology that hold potential to finding a cure. Dr. Egan also discussed the challenges and opportunities presented by these novel therapies as they advance toward the clinical study phases of development. Some of these challenges are very similar to what other rare disease communities are facing as the research of gene therapies increases. For clinical research, recruitment and retention in these trials (that can have a follow-up time of at least 5 years) need to be broached carefully, so participants understand the potential benefits and risks that await.

Excitement around Trikafta approval.

A week and a half before the conference, FDA’s approval of Vertex’s Trikafta was announced. With this approval, 90% of the CF community have a treatment option, which is an outstanding achievement. There was excitement around the approval and what this means to those with CF. What we are hearing from sites is that this also means ongoing clinical research studies are likely to have some delayed enrollment as patients start taking Trikafta. The delay will typically be the result of getting on to a stable dose to meet inclusion criteria, in addition to reduced resources at the site, as more patients are requesting appointments to switch onto Trikafta.

In the second plenary, Jane Davies, MD, MBChB, MRCP outlined the progress and promise of highly effective CFTR modulator therapies and the potential impact that Trikafta could have on this population. Whilst celebrating the success of effective modulator therapy, Dr. Davies also discussed challenges that remain, including treatments for people with rare mutations, caring for a patient population that has grown and aged, and providing access to CFTR modulators in more regions of the world.

CFTR modulators are not expected to eliminate the need for additional chronic therapies and drugs. While there is potential that CFTR modulators offer an opportunity to restore function earlier in life and alleviate a lifetime of lung damage that patients fight into adulthood, patients and families have expressed that reducing the treatment burden is a high priority and even patients on effective modulator therapies are not commonly reducing their other treatments. So while daily care has become increasingly effective, it remains complex and burdensome. This highlights the need for additional treatments and a cure for those with CF.

We will not stop until CF stands for Cure Found.

Current NIH director Francis Collins and his team helped discover the cystic fibrosis gene and he emphasized that the recent approval of Trikafta means that 90% of the community have the potential to receive a remarkable treatment; however, there are still patients with CF who might not benefit from this new therapy (including individuals with rare and nonsense mutations) and we must not abandon the 10% of people for whom these drugs will not provide benefit. Work towards finding a cure for all is just getting started.

A new era in CF research is beginning. The CF Foundation recently unveiled the “Path to a Cure” initiative, which will focus on finding treatments for the underlying cause of CF and a cure for every person with CF. The CFF is challenging academia and industry to accelerate progress in CF drug discovery and development. To help this ambitious initiative, the foundation intends to allocate $500 million to the effort through 2025.

This new era means that other recruitment strategies and study designs should be considered to enroll and execute a successful trial. Understanding the new patient population will be critical, and will require being cognizant that the baseline disease severity will vary across the population. New clinical trials in the era of modulator therapy may also require new endpoints, as incidence or severity of common endpoints such as pulmonary exacerbations may change. Innovative study designs should be considered, but will require an increased amount of regulatory interaction.

Despite this remarkable progress there are significant needs that remain. As the CFF president and CEO, Preston W. Campbell, III, M.D, stated “Don’t stop dreaming of a day when all people with CF can say, ‘I used to have CF’.” Prioritizing innovative approaches to find a cure is at the forefront of the CFF’s mind and a recurring theme at the conference was the sentiment that the most important and challenging work lies ahead – until CF stands for Cure Found.

Need support designing and executing your next CF trial? Ask our experts for help.

Jamie Arnott, RN, BSN, OCN^®, Rho Project Director, received her undergraduate degree in Nursing from the University of North Carolina at Chapel Hill.  She has extensive experience from both the CRO and sponsor perspectives in the oversight and management of clinical trial operations and outsourcing with more than 12 years’ experience in project management and over 20 years’ experience in healthcare as a practitioner and manager.  Prior to her tenure at Rho, Ms. Arnott was the Director of Clinical Trial Operations for a biotechnology company where she provided oversight and management for all clinical activity for up to four concurrent INDs.  Ms. Arnott has broad therapeutic experience with ENT indications, cystic fibrosis, and multiple oncology indications, including ovarian cancer, hematological malignancies, and advanced solid tumors; she has pediatric experience both within the oncology field as well as orphan diseases. 

Kristin Gabor, PhD, RAC, Research Scientist, has over a decade of experience in writing and editing scientific documents and publications across a variety of biological, clinical, and regulatory fields, which includes several publications in peer-reviewed scientific journals.  Dr. Gabor has led and participated in the authoring and preparation of clinical study reports, clinical protocols, annual safety reports, modules of regulatory submissions (NDA, IND, etc.), and other regulatory documents in a variety of therapeutic areas.  She has also coordinated document review for regulatory submissions and led the management of safety review committees for clinical studies.  She has experience in a broad range of therapeutic areas, including sickle cell disease, allergy, inflammation, and immunology, infectious diseases, rare diseases, atopic dermatitis, multiple sclerosis, and cystic fibrosis.  Dr. Gabor earned an interdisciplinary PhD in Functional Genomics from the University of Maine and subsequently received an Intramural Research Training award from the NIH/NIEHS for her postdoctoral studies investigating the role of cholesterol metabolism and cell membrane perturbations in regulating the innate immune response in a rare genetic disease.  Dr. Gabor received her Regulatory Affairs Certification from the Regulatory Affairs Professionals Society (RAPS) in 2018 and is a current member of RAPS and the North Carolina Regulatory Affairs Forum (NCRAF).

Nancy Woody, MA, PMP, Senior Project Manager, has over eight years of project management experience in a clinical research organization (CRO) supporting and leading Phase 1 through 4 global and regional trials. Prior to working at Rho, Ms. Woody worked primarily on late phase and real-world evidence research studies and the collection of patient outcomes in standard of care settings and existing data sources. She has provided leadership to cross-functional clinical research projects and teams, virtually and co-located, in a wide variety of indications including Rare Disease (cystic fibrosis), CNS (Alzheimer’s, Multiple Sclerosis, spine pain, women’s pain, etc.), endocrinology (Diabetes) and oncology (Multiple Myeloma). As the project manager, Ms. Woody’s responsibilities include the creation and maintenance of project management plans, advising on operational strategies and mitigation plans, close collaboration with sponsor contact, and management of vendors, study team resources, timelines and budgets. She has a background in intercultural training and conflict resolution, which has helped to inform her work in risk management and mitigation on complex trials and within diverse teams. Ms. Woody is a certified Project Management Professional and received her Master’s degree in Intercultural Relations from Lesley University and a B.A. in Communication Studies from the University of North Carolina at Chapel Hill.