P231: Leveraging Oncology Innovations for Advancements in Neurology, Infectious Disease, Rare Disease Clinical Trials and Research
Poster Presenter
Margaret Studzinska
Senior Director, Regulatory and Medical Writing
MMS Holdings United States
Objectives
Explore how innovations in oncology clinical trial designs and research are being applied to neurology, infectious disease, and rare disease therapeutic areas.
Method
We reviewed the use of adaptive trial designs, master protocols, surrogate/intermediate endpoints, and regulatory initiatives from oncology to neurology, infectious disease, and rare diseases, analyzing data from clinical trials and regulatory programs (1992-2024) available in the public domain.
Results
Adaptive trial designs and master protocols, initially developed for oncology, have been successfully implemented in neurology, infectious disease, and rare disease trials. The FDA's guidance on adaptive designs and master protocols has provided a framework, leading to a noticeable increase in their application across various indications. These methodologies allowed for mid-study modifications, improvement in trial efficiency, and patient outcomes. Large-scale trials such as NCT02735707 trial for pneumonia and NCT06384573 for Alzheimer's disease have utilized these principles showing to improve trial efficiency and patient outcomes. Diagnostics and biomarkers have also seen significant advancements, with 44 companion diagnostics (CDx) assays approved by the FDA by the end of 2020, facilitating precise patient stratification and targeted therapies. Although, CDx is predominantly used in oncology, other biomarker-defined subpopulations in the rare disease space benefit from personalized treatment strategies. Similarly, the use of surrogate/intermediate endpoints was pioneered in oncology, but they have not yet been broadly adopted across other indications. The definitions of surrogate/intermediate endpoints can vary across indications, e.g., in oncology, endpoints like progression-free survival (PFS) and overall response rate (ORR) are commonly used for accelerated approvals. In contrast, non-oncology indications often rely on more traditional endpoints, leading to a higher proportion of traditional approvals. The FDA's Project Orbis and RTOR initiatives further supported the application of these innovative trial designs, with the CoGenT Global pilot program extending these principles to cell and gene therapies for rare diseases. Real-world evidence (RWE) has been increasingly utilized in regulatory decision-making across various indications, enhancing the evaluation of drug safety and effectiveness with oncology indications leading the use of RWE.
Conclusion
The adoption of adaptive trial designs, master protocols, and surrogate/intermediate endpoints from oncology into neurology, infectious diseases, and rare diseases has led to significant benefits in trial efficiency, patient stratification, and treatment efficacy. These innovative approaches align with the FDA's vision for personalized medicine and have the potential to accelerate the development of targeted therapies for patients with unmet medical needs. Continued collaboration and innovation in this field are essential for further advancements in clinical trial design and personalized medicine. Oncology continues to lead the way, with other therapeutic areas gradually adopting these innovations. Regulatory guidance plays a crucial role in facilitating these transitions, ensuring that trial designs remain robust and patient-centric.
