A rare disease advocate, unhappy with FDA’s draft guidance outlining accelerated approval, is rallying congressional support to push for changes in the final document.

The EveryLife Foundation for Rare Diseases said FDA’s draft guidance on expedited approval programs does not address rare disease needs and does not meet the congressional intent outlined in the 2012 FDA Safety and Innovation Act.

It is asking rare disease patients to help Rep. Gus Bilirakis, R-Fla., a member of the Energy and Commerce Committee, gain members’ signatures on a letter to FDA outlining problems with the draft guidance’s lack of acknowledgement of rare disease issues.

The draft guidance “does not move accelerated approval forward as a legitimate pathway for drug approval within the rare disease community,” according to the letter.

“FDA needs to provide a clear, workable framework for the rare disease community to be able to use accelerated approval on a consistent basis with transparent uniform criteria.”

FDASIA, which reauthorized prescription drug user fees and created the generic drug and biosimilar user fee programs, also included a section expressing congressional sentiment that FDA should encourage more use of accelerated approval in the hopes of making more novel treatments available sooner. The language largely restated existing regulations, however Also see "TREAT Act Wants Accelerated Approval Change, But Uses Existing Language" - Pink Sheet, 20 February, 2012..

The law required new guidance to implement the changes with specific consideration of issues associated with rare and very rare diseases.

“Despite this, the guidance does not mention orphan drugs, rare diseases, or very rare diseases,” the letter states. “The guidance also does not specifically mention the challenges that rare diseases have due to having a small population set, making traditional approval difficult.”

FDA issued the draft expedited approval guidance in late June, which was intended, in part, to define the differences between programs like priority review, breakthrough therapies and fast track Also see "FDA To Provide Expedited Approval Desktop Reference" - Pink Sheet, 29 October, 2012..

It also is intended to help sponsors better understand accelerated approval. FDA said in the guidance that it would remain flexible in determining the evidence needed for a sponsor to gain access to the pathway ([A#00130701003]).

Guidance Needs More Evidentiary Clarity

The EveryLife Foundation wants the guidance to better define how accelerated approval could be used to develop orphan drugs, including the evidence that would be required to use the pathway.

FDA did not make those requirements sufficiently clear, according to the letter.

“The guidance presents a rather restrictive set of evidentiary criteria,” the letter states. “FDA needs to develop and clearly define the degree of evidence and the robustness of evidence correlating to the surrogate endpoint. FDA must also develop what level of evidence is acceptable when clinical outcome data may not be available due to the rarity of the disease.”

Foundation President Emil Kakkis and others have been working on a white paper that seeks to clarify how rare disease sponsors can use surrogate endpoints and biomarkers and the accelerated approval pathway. They wrote in the paper that the existing standards do not encourage predictability and could hurt investment in the space.

Despite the outside push, FDA has argued that general standards may not be possible for biomarker and surrogate endpoint validation. The agency said validation decisions likely will continue being made on a case-by-case basis.

Robert Temple, FDA deputy Center for Drug Evaluation and Research director for clinical science, also said the agency should give more detail and examples of biomarker and surrogate endpoint approvals Also see "Biomarkers In Orphan Studies Still Need Past Experience, FDA Says" - Pink Sheet, 27 May, 2013..

FDA has maintained that it has been consistently flexible when it comes to evidentiary standards for orphan products Also see "Regulatory Flexibility Staring Contest: Will Industry Or FDA Blink First?" - Pink Sheet, 24 October, 2011..

Kakkis has argued agency predictability may be more important Also see "Regulatory Freelancing: Rare Disease Group Hopes To Shape FDA Guidance" - Pink Sheet, 22 April, 2013..

Guidance To Be Finalized In 2014

It is unclear what, if any, changes the agency may make to the draft expedited approval guidance.

Written comments on the document are due Aug. 26. So far, none have been posted to the docket. FDASIA requires the guidance to be finalized one year after the draft is issued, which would be late June 2014.

Congressional pressure may affect FDA’s appetite to adjust the guidance, especially if members feel strongly that the agency did not meet the legislative mandate.

Ultimately, it may remain up to FDA to do a better job of advocating for more use of accelerated approval. Temple has said FDA already had much of the new authority in FDASIA, but it must learn to use it and do a better job communicating it to industry and others ([A#00121224015]).

FDA Accelerated Approval For Rare Diseases Again Under Congressional Pressure

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