LONDON –
Dr. Emily S. Gorell
Of 85 patients with the recessive dystrophic type of EB (RDEB) who were surveyed through the EBCare Registry, 39 had available data from the validated quality of life in EB (QOLEB) questionnaire. Those with the largest wounds (7.5 cm or greater) had an average QOLEB score of 27, compared with 22.5 for those with wounds ranging from 2.5 to 7.5 cm in size, and a score of 14 for those with wounds less than 2.5 cm in size. The maximum score on the 17-item questionnaire is 51, with the higher the number, the greater the impact on quality of life.
“Large wound areas were seen more frequently in chronic open wounds, similar to findings in separate studies,” Emily S. Gorell, DO, a postdoctoral clinical research fellow in dermatology at Stanford (Calif.) University, and associates reported in a poster presentation at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association.
“Larger wounds correlate with self-reported disease severity and key clinical manifestations,” they said, which includes history of squamous cell carcinoma (P = .04), anemia (P less than.01), osteoporosis (P = .03), and gastrostomy tube use (P = .02).
In total, 28 adults and 37 children and adolescents were surveyed; the majority (59%) were from North America, with the remainder from Europe (26%) or other countries (15%). Just over half of respondents were female (53%), and about 38% of surveys were completed by the individual rather than a parent or care giver (62%).
Dr. Jean Y. Tang
Dr. Gorell is working with Jean Y. Tang, MD, PhD, professor of dermatology at Stanford. During an oral presentation at the meeting, Dr. Tang observed that wounds could be defined as being recurrent or chronic open wounds. These two types of wounds behave differently, she said, with the latter never fully healing.
Indeed, in the survey, data on 1,226 wounds were collated, with 937 (76%) classified as recurrent – and healing within 12 weeks – but 289 (24%) remaining chronic open wounds, which did not heal for 12 weeks or longer. Some patients have had open wounds for more than 6 years, Dr. Tang noted.
“In our natural history study … you can see that chronic open wounds never reached 100% closure, they hardly ever reached 50% closure,” she said. In contrast, recurrent wounds have a more dynamic nature, healing completely, then reopening time after time. This is important when considering suitable endpoints for clinical trials, she said, as it could make or break some of the novel treatment approaches currently being tested. For instance, the placebo response in phase 3 trials of the topical therapy allantoin might have been high because recurrent wounds were being studied and were more likely to heal with or without active treatment.
“We’ve done a lot of work, it’s been 2 years, and we have benefited tremendously from these data in our negotiations with the FDA [Food and Drug Administration],” Dr. Tang said. “I am glad we did our homework … we were able to convince the FDA that, for a chronic open wound, a meaningful outcome is 50% healing, not 100%.”
Dr. Tang and Dr. Gorell are part of a team looking at gene-corrected autologous cell therapy (EB-101) to help heal large wounds caused by RDEB. The premise is that by replacing the faulty COL7A1 gene in keratinocytes taken from an individual, these skin cells will be able to produce collagen type VII (COL7). After being grown in culture to form epidermal sheets that look like a plastic film, the sheets can then be grafted over an individuals’ wounds.
Dr. Tang noted that the work was the culmination of 17 years’ of hard work by a small group of committed scientists. Preclinical studies started in 2003, when, she said, “the only funding we could get was through the NIH and thankfully some of the patient organizations.”
Initial results with the EB-101 therapy have been promising. Data on the first four subjects included in a seven-patient phase 1/2 study were published 4 years ago (JAMA. 2016;316[17]:1808-17), and the complete data were recently released (JCI Insight. 2019;4. doi: 10.1172/jci.insight.130554). Each trial subject had an EB-101 graft of approximately 35 cm2 (5 cm x 7 cm) transplanted onto three wounds, with three similar wounds used as controls.
At 6 months, 95% of treated wounds had healed by 50% or more, compared with none of the untreated control wounds (P less than .0001). Healing rates at 1 year and 2 years, respectively, were 68% vs. 17% (P = .025) and 71% vs. 17% (P = .019). All grafts were well tolerated and molecular correction was seen to last for up to 2 years in two patients.
EB-101 therapy will be evaluated in a phase 3 study, the VIITAL study, a multicenter, randomized trial involving 10-15 individuals with RDEB; 50% wound healing at 3 months is the trial’s primary endpoint. The trial, funded by Abeona Therapeutics, was given the go ahead by the FDA in December 2019 and has an estimated completion date of March 2021.
Dr. Gorell did not provide a conflict of interest statement. Dr. Tang disclosed receipt of honoraria or consultation fees from Abeona and Menlo Therapeutics and being a stock shareholder in PellePharm and BridgeBio. Dr. Tang also acknowledged receiving research grants from the EB Research Partnership, the Epidermolysis Medical Research Foundation, and the California Institute for Regenerative Medicine.
SOURCES: Gorell ES et al. EB World Congress, poster 29. Tang JYl. EB World Congress, oral presentation.