FDA Releases Guidelines to Push Industry Development of New Therapies

The U.S. Food and Drug Administration (FDA) has released a guidance document to assist and encourage industry in developing new treatment options for the rare skin disorder epidermolysis bullosa (EB).

“The paucity of effective treatment options for EB represents an important unmet medical need,” the FDA emphasized in presenting the document on its website.

The guidance document offers recommendations for investigational products for treating or preventing skin manifestations, including cell and gene therapies. It also addresses specific issues to be considered when designing a clinical trial in EB — including the FDA’s current thinking on trial endpoints, or outcome measures.

The agency’s considerations for trial design focus on study population — which should be adjusted to the intended EB type — and discussion of efficacy endpoints. Those endpoints include the effects of treatments on patients’ signs or symptoms, such as itching, pain, blister prevention, and wound healing.

Noting “there is not yet sufficient clinical trial experience to establish definitive endpoint,” the FDA is strongly encouraging sponsors to meet with the appropriate review division in the early planning stages to get information tailored to each development program.

Discussions should include the choice of the primary efficacy endpoint, and whether it should be an effect on a continuous scale or on specified sized effect — such as complete healing or a specified minimum degree of healing. Such talks should also address the time point for efficacy evaluation.

A last part of the guidance dedicates special considerations for minimizing visits to trial sites and maximizing patient comfort. For instance, sponsors should consider allowing photo or video documentation of wounds at home, or the use of electronic diaries.

Over the last several years, scientists have made progress in their understanding of the cause of EB, identifying the various genetic defects and proteins involved. Research to find a cure for the disease is ongoing and several potential EB treatments are making their way through companies’ pipelines. Some therapies are currently being tested in clinical trials.

Possible treatments include cell-based therapies, protein replacement — in which proteins are injected into the skin to strengthen the layers — and gene therapy. Other strategies to improve quality of life aim to reduce inflammation and speed wound healing.

One example is Krystal Biotech’s KB103, a topical gene therapy for treating dystrophic epidermolysis bullosa (DEB). The product has received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA, and PRIME (priority) designation from the European Medicines Agency.

Based on promising Phase 1/2 trial results, Krystal is planning to launch a Phase 3 pivotal trial before the end of this year, in which the company will study in more detail the effects of KB103 on the treatment of chronic wounds.

In late May, the FDA also granted an RMAT designation to Fibrocell Science and Intrexon Corporation‘s FCX-007, which is a gene therapy candidate for the treatment of recessive DEB (RDEB).

Fibrocell said it expects to complete data collection for the primary endpoint of a Phase 3 trial in the fourth quarter of 2020.  The company would then file a biologics license application in 2021.

Abeona Therapeutics‘ gene therapy candidate EB-101 won RMAT designation in January 2018 to treat RDEB. A Phase 1/2 clinical trial met its primary safety and efficacy endpoints, the company said. A Phase 3 study is expected to start in mid-2019.