EB-101 Helps Heal Chronic RDEB Wounds, Relieve Pain in Phase 3 Trial
Abeona hopes to submit FDA application for therapy's approval by mid-2023
EB-101, an investigational gene-corrected cell therapy, safely and effectively heals large, chronic wounds and eases pain in people with recessive dystrophic epidermolysis bullosa (RDEB), according to top-line data from the Phase 3 VIITAL trial.
“We are very pleased with the topline results from our pivotal VIITAL study, which reinforce the strong value proposition of EB-101 as a potential one-time therapy to both significantly improve wound healing and reduce pain for the most disabling, challenging to treat wounds in patients with RDEB,” Vish Seshadri, CEO of Abeona Therapeutics, which is developing EB-101, said in a company press release.
Patients need less-demanding treatment options for wound healing and pain
“Our patient community needs options to address not only the healing of wounds but also the chronic pain and the acute treatment related pain of daily wound care associated with these wounds,” said Brett Kopelan, executive director of Debra of America and father of a son with RDEB.
“Today’s standard of care comprises hours of brutal and painful wound care, and EB-101’s promise to be a transformational option for RDEB patients is truly exciting,” Kopelan added.
Abeona now plans to use the results — which highlight that the trial met both of its main goals — to support an application to the U.S. Food and Drug Administration seeking the therapy’s approval for RDEB.
According to a recent company webcast, Abeona expects to submit an application between April and June 2023, which means that a regulatory decision on EB-101 may be expected in the first months of 2024.
The company also plans to submit VIITAL’s results for presentation at future medical meetings and for publication in a peer-reviewed journal.
RDEB is caused by mutations in the COL7A1 gene, which is responsible for producing type VII collagen, a key protein for the skin’s structural integrity. As a result, RDEB patients have fragile skin that easily blisters and tears, leading to chronic, open wounds.
EB-101 is a gene-corrected cell therapy designed to restore type VII collagen production in chronic wounds, thereby promoting their healing.
Essentially, the treatment involves taking a patient’s skin cells, growing them in the lab, and genetically modifying them to carry a healthy version of the COL7A1 gene. The genetically corrected cells are then transplanted into the patient’s wounds.
EB-101 has received orphan drug and rare pediatric disease designations, both of which offer incentives to speed its development toward regulatory approval.
I am incredibly enthused to see new clinical evidence of EB-101’s potential to treat the more difficult chronic and large wounds
Launched in 2020, the Phase 3 VIITAL trial (NCT04227106) enrolled 11 RDEB patients with a mean age of 22.5 years (range 6–40 years), and who had large, chronic wounds. These wounds were greater than 20 squared cm in surface area, and had remained unhealed for at least six months and up to 21 years.
A total of 43 pairs of wounds across these 11 patients were included in the trial’s primary analysis, which assessed the proportion of wounds with 50% or greater healing and changes in patient-reported pain after six months.
“Large chronic RDEB wounds are the toughest to treat and often associated with intense chronic pain that significantly impacts the quality of life of RDEB patients, necessitating frequent use of opioids,” said Jean Tang, MD, PhD, VIITAL’s principal investigator and a professor of dermatology at Stanford University School of Medicine.
For each pair of large, chronic wounds, one wound was randomly assigned to be treated with EB-101, while the other was left untreated. Notably, 14 additional wounds received EB-101 treatment, but were not included in the main analysis.
Results showed that a significantly greater proportion of wounds were healed by at least 50% in the EB-101-treated wounds (81.4%) compared with untreated wounds (16.3%) — meeting one of the trial’s main goals.
Also, significantly more wounds treated with EB-101 were 75% healed (75% vs. 7%) or completely healed (16% vs. 0%) relative to the untreated group.
Patients report EB-101 significantly reduces pain during wound dressing changes
EB-101 treatment also led to significant reductions in patient-reported pain during wound dressing changes — assessed by the 10-point Wong-Baker FACES scale — achieving the other main goal of the study.
Specifically, patients reported that pain in treated wounds dropped by a mean of 3.07 points on the scale after six months, compared with a 0.9-point reduction for untreated wounds.
Post-trial exploratory analysis revealed that pain reductions were most pronounced for severe wounds, or those with a pain score of at least six out of 10 at the start of the study.
When looking at 27 severe wounds treated with EB-101, including those from the randomized pairs and those not included in the primary analysis, the team found that pain scores dropped by an average of 5.7 points. This effect was more pronounced than the 3.51-point drop reported for all EB-101-treated wounds, regardless of their severity.
Significant effects of EB-101 in wound healing and pain were observed as early as three months, with results being similar to 6-month findings, Abeona stated in the release.
The therapy was generally well-tolerated, with a safety profile consistent with previous clinical data. Treatment-related adverse events, none considered serious, were reported in four patients and included procedural pain, muscle spasms, and itchy skin.
“I am incredibly enthused to see new clinical evidence of EB-101’s potential to treat the more difficult chronic and large wounds,” Kopelan said.
Seshadri added: “we are grateful to the patients, their families, caregivers, and the patient advocacy groups for their support of this study, and are also thankful for the clinical investigators, study site personnel, and the entire Abeona team who collectively contributed to this milestone achievement.”
EB-101 is also being investigated in an ongoing Phase 1/2a trial (NCT01263379) in seven adults with RDEB. The latest data from that study show that patients continue to experience durable clinical benefits up to eight years after treatment, Seshadri noted in the webcast.
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