perthpest, your question is good. I would hope that the phase 2...

perthpest, your question is good. I would hope that the phase 2 was the icing on the cake re "preliminary clinical evidence". We don't have to provide anything else to achieve BTD. Further to that, "evidence that is sufficient to indicate that the drug may demonstrate substantial improvement in effectiveness or safety over available therapies, but in most cases is not sufficient to establish safety and effectiveness for purposes of approval." See below for more re BTD.

Breakthrough-Specific Changes

The breakthrough therapy designation section contains a massive number of changes.

One of the biggest: FDA has now committed to rolling reviews for some breakthrough products, saying it has "determined that it is appropriate." The measure allows FDA reviewers to review a submission in parts as they are submitted instead of waiting for the entire new drug application to be submitted. In a similar development, FDA said it will also grant breakthrough products access to priority review, but offered few details on this perk.Another key development:

FDA has removed a section committing the involvement of "senior managers" in the review of products given breakthrough product designation. It will now rely more on "experienced review and regulatory health project management staff," it said.

The final guidance also includes a new definition for the term "preliminary clinical evidence," which FDA takes to mean "evidence that is sufficient to indicate that the drug may demonstrate substantial improvement in effectiveness or safety over available therapies, but in most cases is not sufficient to establish safety and effectiveness for purposes of approval." This evidence is generally obtained from Phase I or II trials, FDA said. Such evidence should indicate "a substantial improvement over available therapies." Drugs intended to treat a disease for which there is no currently available standard of care are also eligible for the designation, FDA wrote.If a drug treats the underlying cause of a disease, it should have a "substantial and clinically meaningful effect" on it as well, FDA wrote.

Drugs which inhibit disease progression are also now eligible for the designation.The guidance also contains a brand new part on the use of pharmacodynamics (PD) biomarkers, which FDA says "may be considered a clinically significant endpoint if it strongly suggests the potential for a clinically meaningful effect on the underlying disease." These will only be acceptable in "rare cases," FDA noted, such as for areas where there are no approved therapies.

The guidance also now clarifies that just because FDA grants a product breakthrough therapy designation, that doesn't mean it will obtain approval. "The clinical evidence needed to support breakthrough designation is preliminary," the agency wrote. All drugs need to undergo a more substantial review, it added. If a product is later shown to not merit the designation, it will be rescinded so that FDA may focus its limited resources on other more promising drugs, it continued.

- See more at: http://www.raps.org/regulatory-focu...dited-Programs-Guidance/#sthash.UesY7PdI.dpuf

http://www.raps.org/regulatory-focus/news/2014/05/19013/FDA-Finalizes-Expedited-Programs-Guidance/