Comparing New Therapies for Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB), otherwise known as “Butterfly disease,” is a rare, genetic, and highly burdensome chronic skin disease characterized by blistering and eventual scarring in the dermis of younger patients—eventually leading to a significantly raised risk of skin cancer development.

Needless to say, timely and efficacious treatment options have been long due for patients with DEB. In only just 1 year, that challenge has been met possibly three-fold.

In the first segment of an interview with HCPLive during the Society for Pediatric Dermatology (SPD) 2024 Pre-AAD Meeting in San Diego, CA, Joyce Teng, MD, PhD, professor of dermatology at Stanford University, discussed the burgeoning field of EB treatment options—one that which may grow even more greatly in the coming weeks.

Teng highlighted for HCPLive a trio of unique agents with supporting late-stage clinical data for the treatment of DEB, recessive DEB (RDEB), and/or junctional EB (JEB): the US Food and Drug Administration (FDA)-approved agents beremagene geperpavec (B-VEC; VYJUVEK) and birch triterpenes topical gel (Filsuvez), as well as prademagene zamikeracel (pz-cel). The latter agent is currently awaiting decision on its Biologics License Application with the FDA, with a PDUFA date of May 25.¹

As Teng explained, the disparity between B-VEC and Filsuvez—both approved by the FDA in 2023^2.3—as treatment options is fairly distinct. The former is a herpes simplex virus-based gene therapy applied directly to the wounds of patients with DEB; the latter is a birch bark-based treatment indicated for patients ≤6 months old with either JEB or DEB.

Pz-cel, meanwhile, could be a more tailored option.

“That’s also a gene therapy, using genetically corrected cells derived from patients themselves—so it's a true, personalized approach,” Teng explained. “The genetically corrected keratinocytes will be growing into a sheet of skin without the genetic defect, then grafted back onto the individual where the initial cells were derived from, to correct the area where the disease is affected.”

Teng said all 3 treatments are initially similar in that they would be targeted toward patients with more severe forms of EB; the avenues of care and rates of administration vary greatly, however.

“Of course, it's a little more complicated process that will require to have the skin graft performed in a major tertiary care center,” Teng said about pz-cel. “But the advantage of that kind of approach to some of these data are already in the public domain—that the durability of these skin grafts are quite good compared to other products. It can probably tailor to patients that have, for instance, a chronic wound in a particular location of their body that's really, really difficult to heal.”

As an at-home, topically-applied agent, B-VEC warrants less focus on treatment initiation—with the tradeoff being continued administrations. The birch bark-based therapy Filsuvez requires even less clinical nuance and may be considered for treating up to one-fourth of affected body surface areas at a time.

Each agent offers a notable contrast in benefit and feasibility. Teng hopes they complement one another to fulfill the needs in EB.

“I think that all these different therapeutic approaches offer choices and options for patients who are affected to deal with this challenging genetic disorder,” she said.

References

2. ^{Smith T. FDA Completes Bioresearch Monitoring Inspection of Pz-Cel for Recessive Dystrophic Epidermolysis Bullosa. HCPLive. Published February 2, 2024. https://www.hcplive.com/view/fda-completes-bioresearch-monitoring-inspection-of-pz-cel-for-recessive-dystrophic-epidermolysis-bullosa}
3. ^{Smith T. FDA Approves B-VEC Topical Gene Therapy for Dystrophic Epidermolysis Bullosa. HCPLive. Published May 19, 2023. https://www.hcplive.com/view/fda-bvec-topical-gene-therapy-dystrophic-epidermolysis-bullosa}
4. ^{Smith T. FDA Approves Birch Triterpenes Topical Gel for Epidermolysis Bullosa. HCPLive. Published December 19, 2023. https://www.hcplive.com/view/fda-approves-birch-triterpenes-topical-gel-for-epidermolysis-bullosa}