Substantial evidence of effectiveness, which is the FDA’s regulatory requirement for approval, generally consists of evidence from at least two adequate and well-controlled investigations. However, for rare diseases, drug developers often face difficulties in recruiting patients for two clinical trials due to the small number of patients. Hence, substantial evidence of effectiveness for rare diseases is often established based on one adequate and well-controlled clinical trial plus confirmatory evidence (CE). Such CE may include a disease’s well-documented natural history, real world evidence, results from non-clinical animal models, pharmacodynamic (PD) biomarkers, and other sources of data. For some NDA/BLA submissions for rare disease programs, PD biomarkers can play a vital role in providing this confirmatory evidence. This presentation will offer an overview and case examples in which PD biomarkers data were assessed for potential use as confirmatory evidence. The presentation will discuss the scientific basis for the use of PD biomarker data as confirmatory evidence, including the source of the PD biomarker data, being a distinct measure from the primary efficacy endpoint used in the adequate and well-controlled clinical trial, mechanistic support, and exposure-response relationships.
Learning Objectives:
Investigate the regulatory context of using a single adequate and well-controlled investigation demonstrating efficacy to generate substantial evidence of effectiveness with the help of confirmatory evidence.
Explore the role of pharmacodynamic (PD) biomarkers in providing confirmatory evidence of effectiveness, especially within the context of NDA/BLA submissions for rare diseases.
Gain insights into successful incorporation of PD biomarkers into clinical trials for rare disease treatments.