The breakthrough therapy designation (BTD), once awarded to a drug product under development, triggers a rather intensive use of Agency resources, such as providing “early and frequent advice, conduct multidisciplinary meetings involving senior managers, and when appropriate, expedite the review of resultant marketing applications.” The program is designed to “facilitate and expedite” review of promising drugs when early data suggests their utility to treat a serious or life‑threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
However, it is possible, as the development program moves along and additional data are generated from larger and more robust studies, that the information originally supporting the designation may no longer support maintaining the BTD. The newly issued guidance document, titled Considerations for Rescinding Breakthrough Therapy Designation (here), outlines how the Agency keeps an eye on the prize and details how the data generated as the program moves forward may necessitate the FDA rescinding the BTD. The FDA notes that each case is fact‑specific and there may be other factors along the way that sway the Agency to maintain the designation and justify continuation of the program through the approval process, even in the face of less robust data or the emergence of a secondary endpoint
The Agency lists the following general considerations for rescinding the BTD as:
- A different drug is approved to treat the unmet need that informed the rationale for granting the BTD. As a result of this new therapy, the BTD drug no longer meets the BTD criteria regarding substantial improvement over existing available therapies. Note that another drug approved under accelerated approval generally will not be considered sufficient to lead to rescinding the BTD.
- Emerging data for the designated drug no longer support the finding that “preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.” (See section 506(a) of the FD&C Act.)
- The designated drug’s sponsor is no longer pursuing the drug’s development program for the use that was the basis for the BTD.
The guidance provides specific examples of how the considerations for rescinding the designation may apply.
The FDA’s goal is to expedite the approval process when appropriate but give itself an out to conserve its scarce resources should the data no longer support the designation. The bottom line is that if the FDA is to continue to make such a commitment, the data must continue to support and justify its efforts.