How Epidermolysis Bullosa Treatments Went from Blisters to Breakthroughs

When I first met children and adults living with epidermolysis bullosa (EB) at a summer camp in 2001, the severity of the condition and the resilience of those affected left an impression that has shaped my clinical and research career. EB is a group of rare, blistering, genodermatoses that cause skin fragility and wounding due to mutations of various proteins along the basement membrane zone. In 2001, care for EB was constrained by limited resources and an incomplete understanding of the disease. Treatment options were rudimentary and clinical trials were rare. Patients with severe forms of EB, particularly recessive dystrophic EB (RDEB), faced early mortality driven by chronic wounds, squamous cell carcinoma (SCC), malnutrition, infections, and systemic complications.¹

 More than 2 decades later, the EB landscape has changed dramatically. With new Food and Drug Administration (FDA)-approved therapeutics, earlier systemic intervention, improved surgical and nutritional strategies, and an expanding biological understanding, we are beginning to see not only better outcomes but also the possibility of altering the disease trajectory. 

Decades in the Making

In the early 2000s, EB care was limited; many patients relied on basic petroleum gauze for wound care, and silicone dressings existed but were not widely accessible.^2,3 The National EB Registry, created in the 1980s, had concluded data collection and results were beginning to be disseminated.⁴ Systemic complications, such as anemia, malnutrition, osteoporosis, cardiomyopathy, and esophageal strictures, were not yet well understood.^5,6

 The diagnostic tools available at the time also limited precision. Electron microscopy and immunofluorescence mapping could provide data on subtypes but required an invasive skin biopsy. Genetic testing was uncommon, costly, and slow, as it was limited to testing one gene at a time using Sanger sequencing.^7,8 Next generation sequencing was later introduced, allowing multiple genes to be sequenced in parallel. In 2009, genetic testing became more common than biopsies in the diagnosis of EB.⁸ The ability to identify specific mutations allowed for more accurate subtyping and clearer genotype–phenotype correlations.⁹

 In the mid-2000s, based on the work out of Italy in treating junctional EB (JEB),¹⁰ our team at Stanford made the leap from bench to bedside as we began developing a phase 1 clinical trial of ex vivo corrected autologous epidermal grafts for RDEB.¹¹ At that time, there were very few other clinical trials in EB.¹² A major milestone arrived in 2013, when we successfully grafted our first patient. Although early and limited in scale, this achievement demonstrated that gene therapy for EB could be clinically viable.¹³

Clinical Trials Lead To Approvals

 The 2010s and early 2020s ushered in a new era of clinical trials and industry support, culminating with the approval of three products for the treatment of EB.

The EASE trial of birch bark triterpines (Oleogel-S10, Filsuvez®), aimed at decreasing inflammation in EB wounds, enrolled 223 participants across 28 countries, which was the largest EB trial ever conducted. In this study, birch bark triterpines demonstrated acceleration of wound closure: by day 45, 41% of treated wounds achieved complete healing compared to 28% in the placebo arm.¹⁴ Patients also reported reduced pain and decreased frequency of dressing changes.¹⁵

Birch bark triterpines were the first therapy approved for JEB and dystrophic EB (DEB), with European Medicines Agency (EMA) approval in 2022 and FDA approval in 2023.

 At the same time, clinical trials of in vivo gene therapy were being conducted with beremagene geperpavec (B-VEC, Vyjuvek ®), a topical gel that uses a genetically modified herpes simplex viral vector for DEB. The phase 3 GEM-3 trial included 31 patients with RDEB. At 6 months, 67% of B-VEC-treated wounds achieved complete healing, compared with 22% of placebo wounds.¹⁶ In 2023, B-VEC became the first FDA-approved treatment for EB, approved for patients 6 months and older with DEB, with administration to be performed by a healthcare provider. The label was expanded in 2025, when the FDA approved use from birth and allowed caregivers to apply the medication at home. In 2025, B-VEC also received approval from the EMA and in Japan. B-VEC is currently under investigation to treat and prevent corneal abrasions.^17,18

In 2025 we also saw the approval of prademagene zamikeracel (pz-cel, Zevaskyn®), an ex vivo gene therapy of surgically grafted autologous keratinocytes that I had worked on for many years. In phase 3 studies, 43 pairs of chronic wounds were randomized in 11 patients to receive either pz-cel or standard of care. At 6 months, 81% of pz-cel–treated wounds demonstrated at least 50% wound healing, compared to 16% in the standard of care arm.¹⁹ From the phase 1/2a studies, we saw long-term healing at treated sites of up to 8 years.²⁰ The FDA approved pz-cel in April 2025. It is available at selected qualified treatment centers in the United States.

Advances in Clinical Care

 Alongside these clinical trials and approvals, clinical care began to evolve in ways that profoundly improved patient outcomes. Increased early adoption of gastrostomy tubes improved caloric intake and growth.^21,22,23 Anemia became the subject of routine screening and aggressive management.^24,25 Osteoporosis was recognized as a consequence of both chronic inflammation and diminished mobility, and became better screened for and treated.²⁶ New guidelines have been developed to standardize the approach to esophageal strictures.²⁷ Cardiac and renal complications were better characterized.^28,29 Itch was identified as one of the most bothersome symptoms of EB;³⁰ biologics and immunomodulators, approved for other dermatologic conditions, have been re-purposed for EB itch and are currently undergoing additional study.^31,32,33

Wound care underwent its own transformation. Advanced silicone contact layers, silver-impregnated dressings, and antimicrobial foams gradually replaced simple petrolatum gauze.³⁴ We began to differentiate chronic from recurrent wounds, an insight that later proved critical in designing trial endpoints and securing regulatory approvals.^35,36 

Chronic Inflammation and Long-term Care

 Increasing attention is being paid to the role of chronic inflammation in EB, recognizing its contributions not only to wound chronicity but also to fibrosis and carcinogenesis.^37,38 Alongside this, cancer management is also evolving. Artificial intelligence is being evaluated to assist with clinical diagnosis of SCC, which can be challenging.³⁹ Immunotherapies, including checkpoint inhibitors such as pembrolizumab and cemiplimab, have shown encouraging responses in EB-associated SCC.^40,41 Rigosertib, a RAS-pathway inhibitor, is being studied for its potential to slow SCC progression in this population.^42,43 The increased research and treatments offer a new hope for an aggressive and feared complication.

 As patients survive longer, the field is now confronting the needs of adults with EB, a population that scarcely existed in significant numbers 2 decades ago. Transitions from pediatric to adult care are becoming more structured, reflecting a recognition that EB must be managed across the lifespan.^44-46 Dedicated adult EB clinics are emerging, and guidelines on the care of adults with EB are in process.

Coming Soon

 While wound healing and structural repair remain central therapeutic goals, new lines of research are beginning to reshape the broader biological landscape of EB. Gene-editing technologies such as CRISPR offer the possibility of correcting genetic mutations directly. Early studies have demonstrated promising correction efficiencies and stable protein expression.^47,48 Additional clinical trials are currently underway to assess gene therapy in fibroblasts^49,50 as well as mesenchymal stem cells.^51,52 Clinical trials are expanding into EB subtypes that traditionally were overlooked, such as EB simplex.^53-55

 The transformation of EB care over the past 20 years has been striking, and I have felt privileged to be a part of it. What was once a field defined almost entirely by supportive wound care has become a showcase for gene therapy, targeted pharmaceuticals, and multidisciplinary expertise. Although EB remains incurable and continues to carry significant morbidity, the trajectory has shifted; I can only hope that this momentum and pace of discovery will continue or even accelerate. With continued research, collaboration, and innovation, the future for individuals living with EB holds unprecedented promise, defined not only by resilience but increasingly by effective, meaningful treatment as well as hope. n

Dr. Gorell has served as a consultant for Abeona Therapeutics; as an investigator for Abeona Therapeutics, Castle Creek, Chiesi, Incyte, Rheacell, and TWI Biotech; as a prior investigator for Abeona Therapeutics, Krystal Biotech, Menlo Therapeutics, Phoenix Tissue Repair, and Phoenicis; and has served on advisory boards for Abeona Therapeutics, Amryt Pharma/Chiesi, and Krystal Biotech. 

1. Fine JD, Johnson LB, Weiner M, Suchindran C. Cause-specific risks of childhood death in inherited epidermolysis bullosa. J Pediatr. 2008;152(2):276-280. https://doi.org/10.1016/j.jpeds.2007.06.039

2. Schober-Flores C. Epidermolysis bullosa: the challenges of wound care. Dermatol Nurs. 2003;15(2):135-138, 141-144.

3. Denyer JE. Wound management for children with epidermolysis bullosa. Dermatol Clin. 2010;28(2):257-264, viii-ix. https://doi.org/10.1016/j.det.2010.01.002

4. Fine JD, Johnson LB, Suchindran CM. The National Epidermolysis Bullosa Registry. J Invest Dermatol. 1994;102(6):54S-56S. https://doi.org/10.1111/1523-1747.ep12388622

5. Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues. J Am Acad Dermatol. 2009;61(3):367-384; quiz 385-386. https://doi.org/10.1016/j.jaad.2009.03.052

6. Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol. 2009;61(3):387-402; quiz 403-404. https://doi.org/10.1016/j.jaad.2009.03.053

7. Has C, Liu L, Bolling MC, et al. Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa. Br J Dermatol. 2020;182(3):574-592. https://doi.org/10.1111/bjd.18128

8. Phillips GS, Huang A, Augsburger BD, et al. A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa. J Am Acad Dermatol. 2022;86(5):1063-1071. https://doi.org/10.1016/j.jaad.2021.09.065

9. Pathmarajah P, Eid E, Nazaroff J, et al. Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2025;192(5):917-925. https://doi.org/10.1093/bjd/ljaf015

10. Mavilio F, Pellegrini G, Ferrari S, et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006;12(12):1397-1402. https://doi.org/10.1038/nm1504

11. Siprashvili Z, Nguyen NT, Bezchinsky MY, et al. Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Hum Gene Ther. 2010;21(10):1299-1310. https://doi.org/10.1089/hum.2010.023

12. Cohn HI, Teng JMC. Advancement in management of epidermolysis bullosa. Curr Opin Pediatr. 2016;28(4):507-516. https://doi.org/10.1097/MOP.0000000000000380

13. Siprashvili Z, Nguyen NT, Gorell ES, et al. Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa. JAMA. 2016;316(17):1808-1817. https://doi.org/10.1001/jama.2016.15588

14. Kern JS, Sprecher E, Fernandez MF, et al. Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study. Br J Dermatol. 2023;188(1):12-21. https://doi.org/10.1093/bjd/ljac001

15. Bruckner A, Kern JS, Murrell DF, et al. The effect of Oleogel-S10 (birch triterpenes) on procedural pain and dressing change frequency in dystrophic epidermolysis bullosa: analysis from the EASE study. Pediatr Dermatol. 2022;39(5):803. https://doi.org/10.1111/pde.15130

16. Guide SV, Gonzalez ME, Bagci IS, et al. Trial of beremagene geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med. 2022;387(24):2211-2219. https://doi.org/10.1056/NEJMoa2206663

17. Tovar Vetencourt A, Sayed-Ahmed I, Gomez J, et al. Ocular gene therapy in a patient with dystrophic epidermolysis bullosa. N Engl J Med. 2024;390(6):530-535. https://doi.org/10.1056/NEJMoa2301244

18. Krystal Biotech Inc. A double-blind crossover of KB803 and matched placebo for the treatment and prevention of corneal abrasions in dystrophic epidermolysis bullosa. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT07016750

19. Tang JY, Marinkovich MP, Wiss K, et al. Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial. Lancet. 2025;406(10499):163-173. https://doi.org/10.1016/S0140-6736(25)00778-0

20. So JY, Nazaroff J, Iwummadu CV, et al. Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis. 2017;17(1):377. https://doi.org/10.1186/s13023-022-02546-9

21. Kleinman EP, Reimer-Taschenbrecker A, Haller CN, et al. Gastrostomy tube feeding in epidermolysis bullosa: a multicenter assessment of caregiver satisfaction. Pediatr Dermatol. 2023;40(2):270-275. https://doi.org/10.1111/pde.15207

22. Feinstein JA, Jambal P, Peoples K, et al. Assessment of the timing of milestone clinical events in patients with epidermolysis bullosa from North America. JAMA Dermatol. 2019;155(2):196-203. https://doi.org/10.1001/jamadermatol.2018.4673

23. Haynes L, Atherton DJ, Ade-Ajayi N, Wheeler R, Kiely EM. Gastrostomy and growth in dystrophic epidermolysis bullosa. Br J Dermatol. 1996;134(5):872-879.

24. Liy-Wong C, Tarango C, Pope E, et al. Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa. Orphanet J Rare Dis. 2023;18(1):38. https://doi.org/10.1186/s13023-022-02448-w

25. Quintana-Castanedo L, Maseda R, Pérez-Conde I, et al. Interplay between iron metabolism, inflammation, and the EPO–ERFE–hepcidin axis in recessive dystrophic epidermolysis bullosa–associated chronic anemia. Blood Adv. 2025;9(9):2321-2335. https://doi.org/10.1182/bloodadvances.2024015271

26. Kwon A, Hwang A, Miller CH, Reimer-Taschenbrecker A, Paller AS. Osteoporosis and bone health in pediatric patients with epidermolysis bullosa: a scoping review. Pediatr Dermatol. 2024;41(3):385-402. https://doi.org/10.1111/pde.15527

27. El Hachem M, Caldaro T, Lara-Corrales I, et al. Management of oesophageal strictures in inherited epidermolysis bullosa: a clinical practice guideline. Br J Dermatol. 2025;193(3):394-404. https://doi.org/10.1093/bjd/ljaf191

28. Lara-Corrales I, Mellerio JE, Martinez AE, et al. Dilated cardiomyopathy in epidermolysis bullosa: a retrospective, multicenter study. Pediatr Dermatol. 2010;27(3):238-243. https://doi.org/10.1111/j.1525-1470.2010.01127.x

29. Boudhabhay I, Bellon N, Avramescu M, et al. Prevalence of kidney complications in a large cohort of patients with recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2025;193(1):15. https://doi.org/10.1093/bjd/ljaf271

30. Danial C, Adeduntan R, Gorell ES, et al. Prevalence and characterization of pruritus in epidermolysis bullosa. Pediatr Dermatol. 2015;32(1):53-59. https://doi.org/10.1111/pde.12391

31. Bellon N, Bataille P, Bonigen J, et al. Experience of dupilumab treatment in inherited epidermolysis bullosa: a short series. J Am Acad Dermatol. 2024;91(2):373-376. https://doi.org/10.1016/j.jaad.2024.04.037

32. Hou PC, Aala W, Tu WT, McGrath JA, Hsu CK. Real-world experience of using dupilumab and JAK inhibitors to manage pruritus in epidermolysis bullosa pruriginosa. Skin Health Dis. 2024;4(5):e445. https://doi.org/10.1002/ski2.445

33. Paller A. Repurposing dupilumab for management of pruritic genetic inflammatory skin disorders: a single-site pilot study. ClinicalTrials.gov. 2024. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT05649098

34. Beraja GE, Gruzmark F, Pastar I, Lev-Tov H. What’s new in wound healing: treatment advances and microbial insights. Am J Clin Dermatol. 2025;26(5):677-694. https://doi.org/10.1007/s40257-025-00953-9

35. Solis DC, Teng C, Gorell ES, et al. Classification of 2 distinct wound types in recessive dystrophic epidermolysis bullosa: a retrospective and cohort natural history study. J Am Acad Dermatol. 2021;85(5):1296-1298. https://doi.org/10.1016/j.jaad.2020.08.118

36. Gorell ES, Eng V, Solis D, et al. Relationships between wound size, clinical manifestations, and quality of life in recessive dystrophic epidermolysis bullosa: a global cross-sectional survey. Acta Derm Venereol. 2020;100(Suppl 220):39-40. https://doi.org/10.2340/00015555-3586

37. South AP, Laimer M, Gueye M, et al. Type VII collagen deficiency in the oncogenesis of cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa. J Invest Dermatol. 2023;143(11):2108-2119. https://doi.org/10.1016/j.jid.2023.05.024

38. Reimer-Taschenbrecker A, Hess M, Davidovic M, et al. IL-6 levels dominate the serum cytokine signature of severe epidermolysis bullosa: a prospective cohort study. J Eur Acad Dermatol Venereol. Published online February 20, 2024. https://doi.org/10.1111/jdv.19898

39. Paller A. Developing a novel artificial intelligence patient app to recognize squamous cell carcinoma in recessive dystrophic epidermolysis bullosa (RDEB): image collection. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT05843994

40. Khaddour K, Gorell ES, Dehdashti F, Tang JY, Ansstas G. Induced remission of metastatic squamous cell carcinoma with an immune checkpoint inhibitor in a patient with recessive dystrophic epidermolysis bullosa. Case Rep Oncol. 2020;13(2):911-915. https://doi.org/10.1159/000508933

41. Piccerillo A, El Hachem M, De Vito R, De Luca EV, Peris K. Pembrolizumab for treatment of a patient with multiple cutaneous squamous cell carcinomas and recessive dystrophic epidermolysis bullosa. JAMA Dermatol. 2020;156(6):708-710. https://doi.org/10.1001/jamadermatol.2020.0304

42. Atanasova VS, Pourreyron C, Farshchian M, et al. Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa–associated squamous cell carcinoma. Clin Cancer Res. 2019;25(11):3384-3391. https://doi.org/10.1158/1078-0432.CCR-18-2661

43. Bauer PJ. A phase II, open study to assess efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa–associated locally advanced or metastatic squamous cell carcinoma. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT03786237

44. Perez VA, Morel KD, Garzon MC, Lauren CT, Levin LE. Review of transition of care literature: epidermolysis bullosa—a paradigm for patients with complex dermatologic conditions. J Am Acad Dermatol. 2022;87(3):623-631. https://doi.org/10.1016/j.jaad.2020.06.083

45. Perez VA, Mulinda C, Bruckner AL, et al. Transition of care in adolescents with epidermolysis bullosa: the provider perspective. Pediatr Dermatol. 2024;41(6):1117-1120. https://doi.org/10.1111/pde.15650

46. Mackenzie E, Lucky AW, Gorell ES. A call to action to address transition of care in pediatric dermatology. Pediatr Dermatol. 2024;41(6):1121-1122. https://doi.org/10.1111/pde.15665

47. Neumayer G, Torkelson JL, Li S, et al. A scalable, GMP-compatible, autologous organotypic cell therapy for dystrophic epidermolysis bullosa. bioRxiv. Preprint posted January 2023. https://doi.org/10.1101/2023.02.28.529447

48. Koller U, Bauer JW. Emerging DNA and RNA editing strategies for the treatment of epidermolysis bullosa. J Dermatol Treat. 2024;35(1):2391452. https://doi.org/10.1080/09546634.2024.2391452

49. Petrof G, Martinez-Queipo M, Mellerio JE, Kemp P, McGrath JA. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol. 2013;169(5):1025-1033. https://doi.org/10.1111/bjd.12599

50. Castle Creek Biosciences LLC. Evaluation of dabocemagene autoficel (D-Fi; FCX-007) for the treatment of wounds due to dystrophic epidermolysis bullosa. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT06892639

51. Aegle Therapeutics. Mesenchymal stem cell extracellular vesicles for the treatment of recessive dystrophic epidermolysis bullosa wounds. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT04173650

52. Kiritsi D, Dieter K, Niebergall-Roth E, et al. Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. JCI Insight. 2021;6(22):e151922. https://doi.org/10.1172/jci.insight.151922

53. BioMendics LLC. A phase II, placebo-controlled, randomized, double-blind clinical trial evaluating TolaSure Gel 5% w/w for epidermolysis bullosa simplex. ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT07027345

54. Teng J, Paller AS, Bruckner AL, et al. Diacerein 1% ointment for the treatment of epidermolysis bullosa simplex: results of a phase 2 study. Acta Derm Venereol. 2020;100(Suppl 220):46-47. https://doi.org/10.2340/00015555-3586

55. TWi Biotechnology Inc. An international, multicenter, randomized, double-blind, vehicle-controlled phase 2/3 study with open-label extension evaluating diacerein 1% ointment for generalized epidermolysis bullosa simplex (EBShield study). ClinicalTrials.gov. 2025. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT06073132