Requesting Breakthrough Therapy designation

In 2012, the United States Congress approved a new provision to the Food and Drug Administration (FDA) Safety and Innovation Act, creating a new “Breakthrough Therapy designation.” This new designation aims to shorten the development and review times for new therapies intended to treat serious or life-threatening conditions, without compromising safety and efficacy standards.

Breakthrough Therapy designation is one of four expedited programs established by the FDA in recent years to help ensure that therapies for serious conditions are approved and available to patients as soon as possible. These programs reflect growing focus within the pharmaceutical industry on the development of treatments for serious diseases.

Nearly 250 requests for Breakthrough Therapy designation were received by the FDA between 2015 and 2017. FDA granted 68 of those requests – and 12 of those products have since been approved by FDA, constituting about 22% of all FDA-approved drugs within that time period.

If you’re interested in pursuing a Breakthrough Therapy designation for your product, here are some of the basics you’ll need to know.

When can Breakthrough Therapy designation be used?

Breakthrough therapy designation can be used when there is potential to address an unmet medical need for a serious condition. Preliminary clinical evidence must indicate that the new therapy may demonstrate substantial improvement over available therapies, on one or more clinically significant endpoint.

What are the key benefits to Breakthrough Therapy designation?

Some of the key benefits of Breakthrough Therapy designation include:

• The sponsor can receive intensive FDA guidance on an efficient drug development program, beginning as early as phase 1 clinical trials.
• The sponsor may be afforded more frequent meetings and communications with FDA, including pre-IND, end-of-phase 1, end-of-phase 2, pre-NDA, or pre-BLA meetings – as well as consultation meetings to discuss clinical study designs, application-enabling data, marketing application structure and content, accelerated approval, and the potential eligibility for priority review of the marketing application.
• The sponsor can receive a “rolling review” of portions of the marketing application before the entire application has been submitted.
• The sponsor also receives the FDA’s organizational commitment, involving senior managers.

At what point in the drug development process can a sponsor request Breakthrough Therapy designation?

Sponsors should consider requesting Breakthrough Therapy designation only after they have preliminary clinical evidence demonstrating that the therapy has a clear advantage over available therapies. The request can be initiated any time during the drug development process, but ideally should be initiated prior to the end-of-phase ll meeting, in order to receive the full benefit of the program.

What are the options for initiating a conversation with the FDA about Breakthrough Therapy designation?

By submitting a preliminary Breakthrough Therapy designation advice form, sponsors can obtain preliminary, non-binding advice from the FDA about whether a formal request is appropriate, based on available data – or whether the request would be too preliminary because it does not currently meet the criteria. This request cannot exceed two pages.

The FDA’s Breakthrough Therapy designation request can be a powerful incentive – with the potential to considerably expedite a product’s approval. However – the FDA only grants a fraction of all Breakthrough Therapy designation requests that are submitted each year.  Sponsors who want to contain costs and get their product to market as fast as possible need to get the format, content and structure of the Breakthrough Therapy designation request right, the first time. And it’s equally important to fully understand the process – and to start the process at the most opportune time for your therapy.