Session 7 – Cell & Gene Therapies Date: 26 July (Friday) 9:00 – 12:00 Venue: 3F, Bldg. A, CTBC Financial Park, Ballroom A
President & CEO
Dr. Kazempour, President & CEO of Amarex Taiwan and its US affiliate, co-founded Amarex Clinical Research in 1998, a full-service contract research organization providing services to the pharmaceutical, biotech, and device communities. Dr. Kazempour serves on the George Washington University Regulatory Affairs Advisory Board, teaching at George Washington University Medical Center and Montgomery College.
Dr. Kazempour has conducted research activities with the National Institutes of Health, pharmaceutical industry and various universities. While at US FDA as a statistical reviewer, he received several awards for innovative problem solving and teamwork along with contributions to the drug approval process. During his tenure at the FDA, Dr. Kazempour also worked as a Senior Staff Fellow and as a Mathematical Statistician responsible for supervising and conducting independent statistical analyses of clinical trials and reviewing statistical sections of submitted protocols and statistical analyses.
His experience in the industry and FDA has allowed him to understand biometrics, quality assurance and quality control from both a sponsor's perspective, as the provider of the data and from a regulatory perspective, as the reviewer of the data. Dr. Kazempour has worked in many therapeutic areas including cell/gene therapy, vaccines, anti-virals, CNS, and oncology as well as medical devices and digital health, as his expertise and knowledge has been a key contributor in the approval of these drugs and devices.
Dr. Kazempour has spent the past 15 years focusing on international drug and device clinical development and has significant experience working with Asian clients. He has successfully assisted Asian clients with different FDA submissions, including IND, IDE, 505(b)2, 510k, PMA, and NDA for botanical, chemical, biological, and device clinical products. Session Speech Title & Synopsis: Challenges and Opportunities in Clinical Design and Statistical Power of Cellular Therapy Products
The design of clinical trials for cellular therapy products often differs from other types of pharmaceutical products. FDA’s major concerns for early clinical phase trial is safety, to identify a safe does, such as maximum tolerated dose. Cellular therapy products may have little or no toxicity; therefore, using biomarkers, such as engraftment and transgene expression is an alternative for primary endpoints.
In this talk we focus on the challenges at the design and analysis stages of clinical development for cellular therapy products. Obviously, there are multiple opportunities that we recommend you to take advantages of at different stages of your clinical development, such as Expedited Programs Designations for Serious Conditions including Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review Designations. In addition to these in 2019 a new designation was introduced specifically for cellular therapy, so called “Regenerative Medicine Advanced Therapy (RMAT) Designation.” This designation allows you to work closely with the FDA on the program’s development and give you ample opportunity to have early interaction with the Division/FDA reviewers to discuss any potential surrogate endpoints or other intermediate endpoints (i.e. Biomarkers) for your primary endpoint.
One of the main challenges at the design and analysis stages is the sample size and power calculation to establish the efficacy. This is because the early studies are conducted in patients rather than healthy volunteers and the noise is typically larger than the other typical New Chemical Entities. Therefore, the original power calculation may not give an accurate assessment of the subject number required to achieve the statistical significance at the end of the trial. To overcome this issue, some sponsors may increase the statistical power from 80% requirement to as high as 90% which really increase the time and cost of completing the trial. We recommend to use Adaptive Trial Design, and to incorporate selected covariates in the primary analysis model. The main purpose of the Adaptive Trial and at least one Interim Analysis is to re-assess the sample size in the middle of the trial to obtain a much better estimate of the sample size based on Conditional Power. Particularly, make sure to select an Adaptive trial design in such a way that there is no statistical penalty. Only by identifying the challenges of these innovative and complicated clinical trial designs, we can offer strategies from different perspectives to overcome these challenges.