Of interest to many drug developers is the October 19 proposed FDA amendment to the Orphan Drug regulations, to address Agency concerns about Sponsor efforts to artificially subset diseases or conditions to obtain the advantages of orphan status during development and after approval.

The revealing preamble to the proposed regulation notes that the existing regulatory language requiring the  disease subset to be “medically plausible” has been mistakenly interpreted by Sponsors to mean any medically recognizable or any clinically distinguishable subset of persons with a particular disease or condition.

Sponsors should consider the following practical questions when assessing whether a subset of a non-rare disease or condition is an appropriate orphan subset:

  • Is the intended subset artificially restricted in any way with respect to the use of the drug to treat the disease or condition?
  • Given that the drug may potentially benefit this particular subset of persons, is there a reasonable scientific or medical basis for believing that the drug would also potentially benefit the remaining population with the non-rare disease or condition or a larger subset of that population?  If not, why not?

An appropriate response to the above questions should be supported by available scientific evidence (e.g. pharmacological or clinical).  In two very recent incidents involving GZP clients, we have noted that the FDA is currently acting on the principles included in the proposed regulations, prior to their finalization.