This designation is designed to expedite the development and review of drugs which may demonstrate substantial improvement over available therapy on one or more clinically significant endpoints. Clinically significant endpoint generally refers to an endpoint that measures an effect on irreversible morbidity or mortality (IMM) or on symptoms that represent serious consequences of the disease. A clinically significant endpoint can also refer to findings that suggest an effect on IMM or serious symptoms, including:
An effect on an established surrogate endpoint
An effect on a surrogate endpoint or intermediate clinical endpoint considered reasonably likely to predict a clinical benefit (i.e., the accelerated approval standard)
An effect on a pharmacodynamic biomarker(s) that does not meet criteria for an acceptable surrogate endpoint, but strongly suggests the potential for a clinically meaningful effect on the underlying disease
A significantly improved safety profile compared to available therapy (e.g., less dose-limiting toxicity for an oncology agent), with evidence of similar efficacy
Pro tip
Breakthrough Therapy designation is requested by the drug company. If a sponsor has not requested Breakthrough Therapy designation, the FDA may suggest that the sponsor consider submitting a request if: (1) after reviewing submitted data and information (including preliminary clinical evidence), the Agency thinks the drug development program may meet the criteria for Breakthrough Therapy designation and (2) the remaining drug development program can benefit from the designation.
The level of evidence required for Breakthrough Therapy designation is higher than for Fast Track designation. Specifically, /gloFast Track designation requires only that non-clinical or clinical data demonstrate the potential to address an unmet medical need, whereas for Breakthrough Therapy designation, preliminary clinical evidence must indicate that the product may demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints. [2]