The US Food and Drug Administration (FDA) on Friday released a draft guidance aimed at helping sponsors develop drugs to treat epidermolysis bullosa (EB), a group of genetic disorders that cause fragile skin and blistering.
FDA says it is developing the guidance to help address the "paucity of effective treatment options" for the disease, as there are no available treatments that cure EB. Instead, the standard of care for EB focuses on wound care and pain management.
According to Dystrophic Epidermolysis Bullosa Research of America, there are five major types and 31 subtypes of EB that affect 1 in 20,000 infants born in the US each year. FDA also notes that the classification of EB is evolving alongside new diagnostic technologies.
While moderate forms of EB can be managed through lifestyle changes and wound care, severe forms of the disease can require intensive intervention and can be disfiguring and sometimes fatal.
"The magnitude of disease burden and unmet medical need posed by EB cannot be overstated," FDA writes.
In the draft guidance, FDA discusses considerations for clinical trial design, including trial population, efficacy endpoints and special considerations for studies involving patients with different types of EB.
Due to the variety of EB types and subtypes, FDA says that the population included in a trial should have documented clinical and laboratory evidence of the specific type of EB that the sponsor aims to treat.
"Because EB subtypes differ in the extent and distribution of cutaneous wounds and the level of skin cleavage, results from an efficacy trial in EB simplex cannot be generalized to the more severe EB subtypes," FDA writes.
For junctional and dystrophic forms of EB, which typically present at birth, FDA says that sponsors should plan on discussing challenges and additional requirements specific to pediatric drug development with the appropriate review division.
FDA says it is "critically important" for sponsors to reach agreement with FDA on the primary efficacy endpoint(s) and magnitude of change that constitute a clinically meaningful improvement before beginning clinical trials.
FDA also says that patient-reported outcomes (PRO) and observer-reported outcomes (ObsRO) should be considered, as such outcomes "provide evidence of how patients feel or function in daily life."
But the agency says it is not aware of any current PRO or ObsRO instruments that are adequate for regulatory assessment purposes, though sponsors are invited to suggest existing or modified PRO/ObsRO instruments for consideration, as well as clinician-reported outcomes.
Sponsors are also advised to focus on developing clinical trials to minimize study visits and maximize patient comfort, as travel can exacerbate skin damage for patients with the condition.