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Update from the top: FDA’s Office of New Drugs ongoing reorganization process

Posted by Karl Whitney on Thu, Jan 02, 2020 @ 11:00 AM
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karlKarl Whitney, PhD, RAC, Assistant Vice President of Product Development, leads multiple integrated drug development programs spanning the development spectrum by planning, managing, and overseeing concurrent manufacturing, nonclinical, clinical, and regulatory activities.

Rho representatives joined regulators, industry scientists, and numerous patient-advocacy groups at CBI's Rare Disease Clinical Development & Access conference in Washington 03-04DEC 2019. During an opening plenary session, FDA's Office of New Drugs (OND) director Dr. Peter Stein shared comments and took questions from the audience. Participants asked a number of questions that indicate a high degree of interest in (and, perhaps, some anxiety about) OND's ongoing reorganization in general and as it might affect specific current projects at the IND or NDA review stage. This reorganization was announced earlier in 2019 and will, among other things, increase the number of offices overseeing review divisions from 6 to 8, and split and/or redesign review divisions to increase the number of divisions from 19 to 27. The reorganization is being implemented in four phases, with the last set to complete by February 2020. Dr. Stein certainly attempted to address some of the audience's concerns. His key message: the ongoing reorganization is intended to improve review processes while ensuring continuity for individual projects. In short, FDA doesn't want to fix what ain't broke.

Instead, the overall goals are to establish more therapeutically aligned, integrated review teams that take an interdisciplinary and 'problem-focused' approach to reviews; and to modernize and standardize review processes across divisions. In the process, he and hOptimization - Business Concept. Golden Compass Needle on a Black Field Pointing to the Word Optimization. 3D Render.is team are taking great care to ensure OND operates smoothly, and that review teams have a re-energized scientific focus for their work.

On the former, he hopes the reorganization will make for more sensible Division groupings. Some large divisions such as Neurology or GI/inborn errors are being split up so that Division Leadership can spend more time on the science and be more externally facing  (eg, at conferences). Individual review teams are being kept together as much as possible when these new divisional groupings are being designed. Further, he has instructed Division heads overall to avoid revisiting prior agreements made between the sponsor and the review team if the team has moved divisions. He believes strongly that it's in nobody's interest to upend established agreements, though he reminded the audience that of course, FDA reserves the right to update its positions as new data accrue. So, sponsor caveat emptor.

On the latter, OND is trying to enhance reviewer consistency and throughput by using a new review template and improved processes that support efficient, integrated reviews of submissions from IND through to approval/post-approval. In addition, a new non-review office called Office of New Drug Policy has been established to support review teams when novel Orange Business Processes Button on Computer Keyboard. Internet Concept.issues come up that lack clear guiding precedent, so that review teams across the OND approach novel issues with greater consistency. Another new cross-cutting office of interest to conference attendees is the planned Division of Rare Disease and Medical Genetics within the new Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine. This group will not have direct review responsibilities but rather will offer 'consultative support' to help review teams properly exercise 'flexibility' in product development programs for example in terms of expected safety database size, a topic that commonly arises, naturally, with rare disease development programs. These rare-disease sponsor projects will still be overseen by the Division that makes the most sense from a therapeutic area - for example, Division of Anti-infectives. The new Division of Rare Disease and Medical Genetics group will also have a mandate to engage outside FDA with patient groups, other regulatory bodies, academia, and even Advisory Committees to ensure they understand realities for rare disease product development. One can only speculate as to why these new responsibilities were not assigned to the longstanding Office of Orphan Product Development.

Overall, the audience took a wait-and-see approach insofar as the reorganization is ongoing and the chips haven't fallen yet. Time will tell if the major goals of the reorganization are achieved by this structure, but Dr. Stein certainly made his best case for the various rationales for the temporary upheaval. Maybe spring cleaning came a bit early to the OND this year....

 

North American Cystic Fibrosis Conference: Key Takeaways

Posted by Lisa Payne on Thu, Dec 05, 2019 @ 09:00 AM
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The 33rd Annual NACF conference continues to be an action packed 3 days bringing together scientists, clinicians, health care providers, and caregivers to discuss the latest advances in CF research, care, and drug development.  These are our top 3 takeaways from the meeting and how they will impact clinical research moving forward.

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.

Medical News on Multicolor Puzzle on White Background.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,Medicine doctor hand working with modern computer interface as medical concept-1 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.

JamieA3Jamie 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-2-1Kristin 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).

NancyWsmallNancy 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.