Optimizing Preclinical Programs and Streamlining Clinical Translation
In today’s rapidly evolving pharmaceutical industry, successfully transitioning from non-clinical to clinical trials is a critical milestone for any drug development program. This process requires careful planning, strategic considerations, and a deep understanding of the challenges and opportunities inherent in this crucial phase. To shed light on this topic, Adrianna Valenciano, Senior Vice President at SSI, moderated a dynamic discussion with Benit Maru, Senior Vice President Medical at SSI, and Steven Zelenkofske, Executive Advisor. Together, they explored the practical and real-world experiences of transitioning from a research organization to a clinical stage.
Key Discussion Points:
– Animal models have limitations in predicting efficacy in humans. Focus on clinical pathobiology and identify animal models that closely recapitulate key disease hallmarks.
– Leverage natural history studies to inform endpoints, patient populations, and disease manifestations in clinical trials.
– Start planning early for operational readiness – drug manufacturing, standardized assays, site capabilities etc. Engage clinical operations experts from the start.
– Have medical/clinical input early to guide translational aspects and start collecting data needed for clinical trials.
– Keep study protocols and execution as simple as possible. Avoid unnecessary complex
Navigating the Transition Phase
One of the major challenges faced when transitioning from non-clinical to clinical trials is the need to predict human responses and obtain human data as quickly and efficiently as possible. As Steven, a seasoned cardiologist with over 25 years of industry experience, shared, the pressure to decrease failure rates and improve predictability in clinical trials is immense. This requires careful consideration of numerous factors, such as identifying relevant animal models, understanding markers of efficacy, and translating findings from small animal models to humans.
Benit, an experienced neurologist, stressed the importance of having a clear understanding of the desired endpoint when contemplating the transition. By working backward from this endpoint, researchers can effectively identify the appropriate patient population, treatment approach, dose, and safety considerations. This integrated approach ensures that research efforts align with the ultimate goal of improving patient outcomes.
Translating Preclinical Data to Clinical Trials
Translating preclinical findings to clinical trials presents its own set of challenges. Several factors must be considered, including the translatability of animal models, the age and route of administration, and the selection of appropriate endpoints. Panelists emphasized that success in this endeavor requires a comprehensive understanding of disease pathogenesis and the careful selection of animal models that mimic the disease course observed in humans.
Additionally, issues with translatability of biomarkers, particularly in complex diseases such as neurodegenerative, cardiovascular, and kidney diseases, were discussed. Steven highlighted the importance of distinguishing between biomarkers that act as surrogates for efficacy and those that accurately reflect the underlying disease pathology. This distinction can significantly impact the development and success of clinical trials.
Leveraging Natural History Data
Natural history data emerged as a valuable tool in informing both non-clinical and clinical strategies. This data provides insights into disease progression, phenotypic manifestations, and the specific mutations present in patients, particularly in rare diseases and gene therapy research. By leveraging natural history data, researchers can identify trends, gaps in knowledge, and potential areas for further research. Furthermore, natural history studies offer a more complete picture by complementing non-clinical data and reducing the risk associated with transitioning to the clinical stage.
Operational Considerations for Successful Transition
Transitioning from preclinical to clinical trials requires careful planning and foresight. It is essential to involve clinical operations early in the drug development process to ensure the selection of appropriate study centers, drug supply, and logistical considerations. Implementing an Integrated Development Plan (IDP) with milestone-based development and clear go/no-go decision points can help streamline the process and optimize resource allocation.
Moreover, early engagement with health technology assessment (HTA) and payer teams is crucial, especially for rare diseases and gene therapies. By proactively addressing market access and patient access concerns, companies can better position themselves for success in a competitive landscape.
Transitioning from non-clinical to clinical trials is a critical phase in drug development. It requires a strategic and integrated approach, taking into account translatability challenges, leveraging natural history data, and addressing operational considerations. By understanding the complexities of this transition and learning from the experiences and expertise of seasoned professionals like Benit and Steven, researchers can navigate this critical phase with confidence and increase the chances of success.