US Food and Drug Administration (FDA) Commissioner Scott Gottlieb testified before the US House of Representatives’ Energy and Commerce Committee on November 30, 2017 about the agency’s implementation of the 21st Century Cures Act, which was signed into law in December 2016 and is designed to help accelerate medical product development.

The law enables the FDA to modernize clinical trial designs and clinical outcome assessments, which will speed the development and review of new medical products, including medical countermeasures, according to information from the FDA. It also provides new authority to help the FDA improve its ability to recruit and retain scientific, technical, and professional experts. It further establishes new expedited product development programs, including those for regenerative medicines, breakthrough medical devices, and authorizes the creation of one or more intercenter institutes to help coordinate activities in major disease areas between the drug, biologics, and device centers and improves the regulation of combination products, according to information from the FDA.

 “I want to commit to you that timely implementation of this legislation is one of our highest priorities,” Gottlieb said in his testimony. “The Cures Act is a defining element of my own policy planning at FDA. When I arrived at FDA seven months ago, I remarked that I couldn’t imagine a better time to be leading the agency owing to two important new opportunities,” he said. “The first is the opportunities offered by new science and technology. Gene and cellular therapies, more targeted drugs, regenerative medicine, digital health tools, and new biomaterials offer the potential for dramatically better, and even curative, therapies for many disorders. The second is the opportunities provided by Congress. The reauthorization of the user fees, and more notably, the Cures Act, offers FDA a new platform to fashion these scientific advances into practical treatments for patients.”

Gottlieb said that the agency will soon releasing a document to outline the agency’s plan for implementation. “To build on what [Congress] asked us to do, we’ll soon release a document that will take full measure of how we’re expanding on the provisions in Cures, to make sure we are continuing to expand on what Congress set out to achieve.”

In terms of expanding provisions for expedited review, Gottlieb said with targeted medicines, particularly in oncology, the FDA is sometimes able to observe earlier, and in some cases, outsized benefits. “For example, we’re currently examining approaches to better expediting review and approval of these products by leveraging FDA’s existing expedited programs,” he said in the testimony.  “Accelerated approval has typically been granted in circumstances where earlier-stage or smaller data sets show benefit for a serious unmet medical need. But that showing of benefit is typically based on the drug’s effect on a surrogate endpoint. In these cases, that endpoint, like tumor shrinkage, is judged to be reasonably likely to predict clinical benefit,” Gottlieb said.

For targeted drugs that the FDA says still require more evidence to understand best clinical use, Gottlieb says the agency might want to approve such a product earlier and require a post-market confirmatory study to validate the finding – similar to an accelerated approval approach. “Congress clarified our authority under FDASIA [Food and Drug Administration Safety and Innovation Act] to grant accelerated approval based on intermediate clinical endpoints,” Gottlieb said in his testimony “We want to better define what’s meant by intermediate endpoints to ensure that product developers with promising drugs take full advantage of this provision and can consider it in a broader range of such settings,” he said.

“As the mechanism of diseases, like cancer, become more clearly defined, and drugs targeting these conditions are more carefully tailored to the underlying biology of disease, we’re going to see more such cases – situations where a new drug offers an outsized survival benefit in a selected population of patients in a smaller, early-stage clinical trial,” he said in his testimony.

One reason Gottlieb says the agency wants to consider accelerated approval in these settings is that it would include authority by the FDA to require confirmatory evidence to support the continued marketing of the drug and an expedited withdrawal mechanism if that evidence fails to confirm the benefit.

“To fully leverage these opportunities, and in keeping with the spirit of Cures, we’re working on a similar proposal for cancer drugs already approved for one indication – approval for a supplemental application, where the approval concerns a second indication, can sometimes appropriately rely on a more targeted data set, like a single-arm study,” Gottlieb said.

Gottlieb says the FDA intends to issue guidance to clarify the circumstances for which the items identified in the proposals are appropriate.

Source: FDA