Regulatory Focus™ > News Articles > Rare Disease Advocate Slams FDA Expedited Approval Guidance

Rare Disease Advocate Slams FDA Expedited Approval Guidance

Posted 07 October 2013 | By Alexander Gaffney, RAC

An advocacy group focused on the needs of patients with rare diseases is pressing the US Food and Drug Administration (FDA) to consider the needs of such patients when developing guidance on expedited approval pathways, and getting some major congressional support in the process.


The Food and Drug Administration Safety and Innovation Act (FDASIA) was passed into law in the summer of 2012, and contained a plethora of provisions intended to both better fund and reform FDA.

One of those provisions, Section 901, called for the re-evaluation and modernization of FDA's expedited approval pathways. FDA had three expedited approval pathways prior to the passage of FDASIA: accelerated approval, fast track designation, and priority review designation. With the passage of the law, a fourth, known as Breakthrough Product Designation (BPD), was created as well.

FDA recently published draft guidance on all four pathways, seeking to clarify their distinct advantages relative to the traditional drug regulatory approval process, as well as instances in which their provisions may be combined.

Section 901: Where's the Guidance?

But while the guidance has been lauded by some as a step in the right direction, a letter to FDA authored by The EveryLife Foundation, a rare disease advocacy group, says FDA failed to meet the original intent of legislators when issuing the guidance.

The 20 September 2013 letter references Section 901 of FDASIA, a provision of which requires FDA to "consider any unique issues associated with very rare diseases."

"[FDA] shall consider how to incorporate novel approaches to the review of surrogate endpoints based on pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical," Section 901 states.

"Despite this statement," the letter says, "the guidance does not mention orphan drugs, rare diseases or very rare diseases." The group also called out FDA for failing to address even in general terms the challenges rare disease populations face when going through the drug approval process.

Rare disease issues have historically included enrollment challenges, as well as difficulties assessing statistical validity of small sample sizes. These issues can be compounded even further in "very rare" diseases, sometimes referred to as "ultra-orphan" populations, referring to populations with diseases so rare they have been "orphaned" by drug developers.

EveryLife: More Specificity on Accelerated Approvals

The letter goes on to call the guidance's evidentiary criteria "restrictive," and requests that FDA "develop and clearly define the degree and robustness of evidence correlating to the surrogate endpoint." Surrogate endpoints are used in some trials when an intermediate measurement offers a reasonable likelihood of indicating an eventual benefit, allowing for conditional approvals contingent on the eventual submission of the full data. They are typically used during the accelerated approval process. However, Accelerated Approval has been associated with some prominent failures, most notably the failure of the breast cancer drug Avastin (bevacizumab), which saw its indication for breast cancer removed in 2011 after additional data showed it did not have a net benefit for patient's overall survival.

As it currently stands, "The guidance the FDA issued does not move Accelerated Approval forward as a legitimate pathway for drug approval within the rare disease community," the letter concludes, noting that its historical use in the rare disease space has "been limited."

The group said it hopes FDA attempts to address these matters in its final guidance-a hope that received the co-signatures of more than 100 members of Congress.


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