FDA Input on Rare Disease Development Needed: PhRMA

Pharmaceutical Research and Manufacturers of America (PhRMA) says rare disease drug development could benefit by FDA providing greater detail and context on the types of evidence that may be considered confirmatory. In comments on rare disease development, the industry group says that because many rare diseases do not have relevant animal models on which to perform nonclinical studies, it would be helpful for FDA to provide information on the use of alternative methods to support rare disease drug development.

Regarding clinical trial designs, PhRMA urges the agency to develop materials to help sponsors identify the circumstances where external data, such as natural history studies or real-world data (RWD) can replace or augment the control arm in Phase 2 or Phase 3 trials. “Information about approaches and/or methodologies and tools to support development of databases, the conduct of natural history studies, and other studies which would be adequate to support regulatory decision making would also be helpful,” it says.

Additionally, the group asks FDA to provide more information on novel surrogate endpoints, especially for slowly progressive rare diseases with heterogenous clinical manifestations. “In terms of endpoint development, we suggest materials be developed to identify the appropriate qualitative research methods that sponsors can use to provide a holistic patient evaluation,” PhRMA says. Because small patient populations and sample sizes limit sponsors’ ability to validate outcome assessments for rare disease populations, the group encourages the agency to “provide information on innovative approaches for novel endpoint validation (such as approaches to the use of nonclinical data, in silico data and artificial intelligence). This could include providing case studies on alternative approaches to the validation of clinical outcome assessments for patients living with rare disease.”