Experimental stem cell therapy eases RDEB symptoms, families report
Developer plans to seek approval in the US, UK, and EU this year
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Children with recessive dystrophic epidermolysis bullosa (RDEB) and their parents reported less pain and itch, better wound healing, and greater participation in daily activities after treatment with Inmune Bio’s Ebstrocel, an experimental stem cell therapy, during the MissionEB trial, according to a new analysis.
The findings build on previously reported MissionEB data, which showed reduced itch and pain in children with intermediate and severe RDEB given the cell therapy. Inmune Bio, which plans to seek regulatory approval of its RDEB cell therapy in the U.S., the U.K., and the European Union this year, announced recently that it has readied the process for commercial-grade manufacturing of CORDStrom, its stem cell platform.
“The study highlights the critical importance of qualitative methodologies in adding to quantitative trial outcomes and capturing the meaningful impact of interventions on the lives of patients and families particularly where quantitative measures may not fully reflect lived experience,” the scientists wrote.
The study, “Mesenchymal stromal cell infusions of umbilical cord-derived mesenchymal stromal cells in children with Recessive Dystrophic Epidermolysis Bullosa (MissionEB): a qualitative sub study of a randomised, double-blind, placebo controlled, crossover, phase 3 trial,” was published in Orphanet Journal of Rare Diseases.
CORDStrom platform being used to develop Ebstrocel
Epidermolysis bullosa (EB) is a group of rare disorders marked by fragile skin that blisters and tears easily, wounds that heal slowly, and severe scarring. Patients often experience itching and pain, may have digestive problems, and are at an increased risk of skin cancer. RDEB, one of its more severe forms, is caused by mutations that disrupt type VII collagen, a protein that helps hold skin layers together.
CORDStrom uses mesenchymal stem cells — stem cells able to grow into certain types of connective tissue — that are derived from donated umbilical cord tissue. Using this stem cell platform, Inmune is developing Ebstrocel, a cell therapy intended to help facilitate wound healing.
The MissionEB trial (ISRCTN14409785) tested whether its cell therapy was safe and effective for children with RDEB. In the double-blind study, participants were randomly assigned to two stem cell or placebo infusions given two weeks apart. After an assessment at nine months, all children were switched to the treatment that they did not receive in the first part of the study using the same dosing protocol.
In the main trial, 34 children received at least one infusion. Results showed no safety concerns and no significant change in the primary disease activity measure, called the Epidermolysis Bullosa Disease Activity and Scarring Index. However, there were trends toward clinically meaningful benefits, particularly in children with intermediate RDEB.
‘I think the worst thing for me is the pain’
To learn more about the treatment’s impact, researchers in the U.K. conducted an interview-based study. In total, they interviewed 10 parents and six children. Thirteen people — eight adults and five children — were interviewed twice, once in each treatment period.
Participants described RDEB as a central part of daily life. Pain, itch, wounds, dressing changes, eating difficulties, and limits on school or play were among the most common issues discussed.
“I think the worst thing for me is the pain because the pain affects everything in general so like with sleeping there’s pain,” said a patient with severe RDEB.
Parents also described the emotional strain of watching their child experience pain and needing to stay alert to skin problems throughout the day and night.
“It actually affects me a lot mentally so you know when just imagine your child crying screaming with pain and you can’t do anything, that literally, apart from breaking your heart,” added a parent.
‘I’m happy to come whenever they call us for the trial’
Families said they were hopeful about the stem cell therapy.
“I’m happy to come whenever they call us for the trial,” one parent said, adding that even a small reduction in pain makes a big difference in real life.
After stem cell infusions, families reported less pain and itch, improved wound healing, and fewer dressing changes. Better sleep, more energy, improved eating, better mood, and greater participation in daily activities were also noted benefits.
“My friend always like comes knocking or saying do you want to play out and I normally say no because I am too tired but now, I can actually go outside and play as well,” said a child with intermediate RDEB.
One child said they played more with their sibling, which the parent linked to the child being less afraid because of reduced pain.
Overall, the reported benefits were more common after stem cell treatment than after the placebo. Although the trial was blinded, meaning families did not know whether the child received the therapy, many participants believed they could tell based on positive symptom changes with treatment in contrast to minimal or no change with the placebo.
There was an overwhelming view that parents would let their child have the treatment if there was even the smallest improvement in their symptoms, because of their view that the improvement in symptoms led to improvement in quality of life.
Negative experiences were limited and were generally related to the infusion process. A few participants reported issues including a faster heart rate, tiredness, or an unusual smell.
All parents interviewed said they would be willing for their child to receive the treatment again.
“There was an overwhelming view that parents would let their child have the treatment if there was even the smallest improvement in their symptoms, because of their view that the improvement in symptoms led to improvement in quality of life,” the scientists wrote.
Overall, the researchers said the interview findings support the perceived benefit of Ebstrocel in children with RDEB, especially those with milder disease, and help explain treatment effects that may not be reflected in standard clinical scoring systems.
“Interview findings regarding symptom improvement and participants’ ability to discern active treatment shed light on its perceived benefit in RDEB, especially in milder RDEB patients,” the team concluded.
Inmune Bio is planning to start a Phase 3 clinical trial to further test the stem cell therapy.
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