WASHINGTON, DC — An investigational cream containing a concentrated form of an old active ingredient might offer new hope for patients with all three major types of epidermolysis bullosa, results from a phase 2b trial suggest.
At 2 months, wound healing was significantly better with a 6% concentration of SD-101 (Zorblisa, Scioderm) than with vehicle placebo in patients with epidermolysis bullosa.
In 2013, SD-101 was granted breakthrough therapy designation by the US Food and Drug Administration for the treatment of patients with inherited epidermolysis bullosa. Such designation "is very unusual, but of course reflects the terrible issues we've had with this disorder," said Amy Paller, MD, from the Feinberg School of Medicine at Northwestern University in Chicago.
The SD-101 6% concentration is now being tested in a larger phase 3 study, Dr Paller reported here at the American Academy of Dermatology 74th Annual Meeting.
The active ingredient in SD-101 is allantoin, a diureide of glyoxylic acid that has long been used as a moisturizer and wound healer in many over-the-counter products, including cosmetics and lotions. The SD-101 formulation is a stable, highly concentrated form of allantoin.
"It's great that we can have a human trial in something that's very safe. It's in a lot of over-the-counter medications, including some cited to have wound-healing abilities, but in very low concentrations and has not been well studied," Dr Paller explained.
This is an "early study, but if it improves wound healing, it will be wonderful because these patients suffer so much," said Inder Dhillon, MD, a dermatologist at the Kaiser Permanente Medical Group and clinical instructor at the University of California, San Francisco.
Currently, options for the treatment of the severe blistering and scarring associated with epidermolysis bullosa are limited to topical emollients, such as petroleum jelly or Aquaphor, and various dressings. "The 6% strength sounds far more effective," Dr Dhillon told Medscape Medical News.
Phase 2b Study Points to Effective Strength
The phase 2b study involved 11 patients with epidermolysis bullosa simplex, the most common and mildest type, which typically causes superficial blistering and mucosal involvement; 29 patients with recessive dystrophic epidermolysis bullosa, which is associated with growth retardation, anemia, skin cancer, and scarring that can lead to esophageal narrowing; and eight patients with junctional epidermolysis bullosa, the least common and most severe type, which is associated with severe blistering, infections, and usually early death. The mean age of the 48 patients was 12.2 years (range, 6.0 months to 43.6 years).
In the initial 3-month double-blind phase of the study, the patients were randomized to receive SD-101 3%, SD-101 6%, or vehicle placebo applied topically once a day. The baseline target wound sizes ranged from 7.6 cm² in the SD-101 6% group to 9.5 cm² in the placebo group.
Complete wound closure at month 1 — the primary end point of the study — was better with SD-101 6% than with placebo in the intent-to-treat population of 48 patients (P = .37). The same was true for complete wound closure at month 2, the primary end point in the ongoing phase 3 study (P = .24).
In the evaluable population of 45 patients — two were lost to follow-up and one did not have an identifiable qualifying lesion — complete wound closure at month 2 was significantly better with SD-101 6% than with placebo (P = .04).
|Complete Wound Closure||SD-101 3% (%)||SD-101 6% (%)||Placebo (%)|
|All 48 patients|
|At month 1||38||53||41|
|At month 2||44||60||41|
|45 evaluable patients|
|At month 2||44||82||41|
Although the study was not powered to assess the significance of median time to target wound closure — a secondary end point of the study — it was faster "by far" with SD-101 6% than with SD-101 3% or placebo in the intent-to-treat population (40 vs 86 vs 91 days), Dr Paller reported. The same was true for the evaluable population (30 vs 86 vs 91 days).
Treatment-emergent adverse events were generally similar in the treatment groups, although there was more fever with SD-101 6% than with placebo (33% vs 12%), more application site pain (13% vs 6%), and more pruritus (13% vs 6%). There were no deaths, severe adverse events, or serious adverse events with SD-101 6%.
"I'm happy to say that there were no significant problems with side effects," Dr Paller said.
In fact, "because allantoin has been around for a long time, most likely it's going to be harmless," Dr Dhillon said. "Of course, increasing concentrations might make a big difference. It will remain to be seen, but it looks like a pretty safe ingredient."
This cream doesn't address the underlying pathophysiology of epidermolysis bullosa, which results from mutations in several genes. However, "if something is effective in healing these wounds much faster than we can heal them now, I think it will be a wonderful thing, even if it doesn't affect the basic disease process," Dr Dhillon explained. "Markedly enhanced wound healing would be highly desirable and welcome."
In a subsequent 12-month extension of the phase 2b trial, which 28 of the 42 patients enrolled completed, the total body surface area affected by wounds or lesions decreased by 3.41% (P = .06).
Scioderm began the phase 3 trial in 2015, on the basis of early phase 2b results. So far, about half of the anticipated 150 patients has been accrued. Top-line data are expected later this year.
Dr Paller is an investigator, consultant, and investigator for Scioderm (recently acquired by Amicus), and reports financial relationships with Alexar Therapeutics, Amgen, Anacor Pharmaceuticals, Celgene Corporation, Dermira, Eli Lilly and Company, Galderma Laboratories, Novartis Pharmaceuticals Corp., Pfizer, Regeneron, Shire, and Stiefel. Dr Dhillon has disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 74th Annual Meeting. Presented March 6, 2016.
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Cite this: Investigational Cream Promising for Epidermolysis Bullosa - Medscape - Mar 08, 2016.