Developing standards for breakthrough therapy designation in oncology

Abstract

In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential "breakthrough" drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a "Breakthrough Therapy", the U.S. Food and Drug Administration (FDA) and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy.

Figure 1

Development timelines for (A) standard drugs/biologics and (B) Breakthrough Therapies, and respective companion diagnostics (co-Dx). While standard investigational drugs typically go through the traditional three phases of clinical testing, Breakthrough Therapies will have a condensed or abbreviated development program. The type of pivotal trial for a Breakthrough Therapy will vary depending on its characteristics and those of the disease it aims to treat.