Editor’s note: This is the second in a two-part series on epidermolysis bullosa. The first part, about the complications caregivers experience with the disease, can be found here.
Despite the recent clinical-trial failure of SD-101, a once-promising skin cream, efforts are building to better understand epidermolysis bullosa (EB) and find relief, if not a cure, for those with the devastating disease.
Currently, there is no U.S. Food and Drug Administration (FDA)-approved treatment for EB, a group of extremely painful and disfiguring skin disorders that affect children from birth. Care basically consists of pain management, as well as bandaging and cleansing open wounds to avoid infection. Feeding tubes, antibiotics and hand and esophageal surgeries are also regularly used to treat EB symptoms.
Amicus Therapeutics‘ investigative treatment SD-101, also known as allantoin cream, had the potential to become the first FDA-approved therapy for those with EB.
Engineered to treat EB’s hallmark skin blistering and lesions, SD-101 ultimately was found to have not much more effect during late-stage clinical trials than placebos, and did not meet primary and secondary treatment goals, Amicus announced Sept. 13. The biotech company said it had no plans for more studies and will not market the product.
Other therapies look good
Brett Kopelan, executive director of DEBRA of America, a nonprofit that supports and raises research funds for the EB community, called the announcement “bad news.” Still, he was upbeat about prospective treatments such as EB-101 for patients with the recessive dystrophic type of EB.
The FDA recently recommended that Abeona Therapeutics accelerate its clinical development program of the gene therapy. “It’s good news, exciting,” said Kopelan, who has a daughter with EB. The pivotal Phase 3 trial is expected to start early next year.
“The FDA guidance is an important milestone in our clinical development plant for EB-101, and we are pleased to be moving forward into a registrational Phase 3 clinical study in 2018,” Abeona’s president and CEO, Timothy J. Miller said in a news release. “We are grateful that the FDA has recognized EB-101 as rare disease pathology to offer significant therapeutic benefit for RDEB patients.”
Patients with recessive dystrophic EB lack the collagen C7, a component responsible for maintaining different layers of skin attached to each other. The investigational gene therapy is supposed to add the correct COL7A1 gene to skin cells. In turn, the new gene will spark production of the missing C7 protein and help repair damaged skin.
Bone marrow transplants
At the University of Minnesota Masonic Children’s Hospital, a cure-focused EB clinical trial is underway in the form of bone marrow transplants. The most recent part of the treatment study involves receiving a transplant from a half-matched donor like a sibling or parent, and post-transplant, multiple infusions of certain stem cells.
“The work out of Minnesota is truly groundbreaking,” Kopelan said. “But it’s still being studied to see if it’s an effective treatment. It’s also important to weigh the risks, both long and short.”
Elsewhere, EB researchers from around the world are looking into new therapies. Stem cell transplants, protein replacement and gene therapies are moving forward, and a host of wound care therapies are being tested, according to ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
Scientists are studying, for example, the CelluTome system to treat lesions; the treatment of itch in EB patients; biochemical correction of severe EB; Alwextin cream in treating EB; and the effectiveness of granulocyte colony stimulating factor in patients with recessive dystrophic EB.
Also under study is gentamicin therapy for recessive dystrophic EB patients with nonsense mutations; the safety of Fibrocell’s gene therapy candidate FCX-007 for recessive dystophic EB; the long-term safety of the cream Zorblisa; and the topical sirolimus 2% for patients with EB simplex.
Exciting news about diacerein 1%
Kopelan is particularly enthusiastic about Castle Creek’s diacerein 1% ointment (CCP-020), which blocks interleukin-1 beta (IL-1b), an inflammatory signaling pathway in EB simplex, the most common type of EB. The hope is that by diminishing the inflammatory pathway associated with EB, CCP-020 can strengthen tissue and support healing. The first patient was enrolled in the study this past spring.
“I’m very excited about diacerein,” Kopelan said. “Castle Creek is a great biotech with a great team. It’s nice that a drug is really looking at the simplex market in general and as a prophylactic therapy.”
However, Kopelan is less sanguine about KeragelT cream, in wide use worldwide. The keratin-based gel can be used in the regular management of injured and uninjured skin of those with EB to make skin more robust and potentially less vulnerable to breakdown. It gained FDA approval in 2009. “KeragelT has not been, nor is it going to be, subject to a rigorous clinical trial through the FDA,” he said.
The tried and true may not work
Some patients and caregivers rely on existing topical treatments such as Aquafor ointment and Mepilex Transfer Dressing, while others routinely use silver ointment or natural substances like coconut oil or medical-grade honey to help manage pain and wounds, and to reduce the risk of infection. However, most topical products are not supported by clinical evidence regarding their safety and efficacy for treatment.