Shire plc, a specialty biopharmaceutical company focusing on  ADHD, HGT and gastrointestinal, has started phase III study designed to evaluate the efficacy and safety of ABH001, its dermal substitute therapy, for the treatment of non-healing wounds in patients with Epidermolysis Bullosa (EB), a group of rare genetic skin disorders that begin to manifest at birth or early childhood and occur in approximately 19 per one million live births in the US.

The new phase III study is a multi-site, prospective, randomized, open-label, intra-subject controlled trial evaluating the efficacy and safety of ABH001 to initiate healing and reduce the wound surface area of selected stalled, chronic cutaneous wounds associated with generalized EB.

“People affected by EB suffer skin blisters and almost constant, acute pain and scarring,” said the study’s principal investigator, H Alan Arbuckle, MD, Section Head Paediatric Dermatology Kaiser Permanente Colorado, Wound Care Consultant, Epidermolysis Bullosa Centre of Excellence, The Children's Hospital, Aurora Colorado. “The current standard of care is daily wound care, bandaging and pain management. I am excited to be involved in testing the efficacy and safety of ABH001 as a potential treatment option for these patients.”

ABH001 for EB has been granted an orphan drug designation in the US and EU, and has also received Fast Track designation from the US Food and Drug Administration (FDA), which is aimed at facilitating the development and expediting the review of drugs and biologics that fill an unmet medical need. In addition, the European Medicines Agency’s Paediatric Committee has agreed on a pediatric investigation plan for ABH001 for the treatment of EB.

Approximately 20 subjects with generalized EB aged three years and older are planned to enroll in the trial, which is targeted to be conducted in 10 to 15 sites across the US, Europe and Canada. The study will comprise ABH001 applications sufficient to cover the surface area of the wound, applied topically every four weeks with protocol-specified dressings until healed or for up to 24 weeks.

“We are excited that Shire Regenerative Medicine has launched this trial,” said Brett Kopelan, executive director of the Dystrophic EB Research Association of America (DebRA ) and father to a five-year-old girl with recessive dystrophic EB. “While there is currently no cure for EB, I am encouraged that ABH001 is targeting the chronic wounds that are the hallmark of this disease. I applaud Shire for pushing this forward and look forward to working closely with them as the trial progresses.”

“We are very eager to begin evaluating ABH001 as a potential wound treatment option for people with EB. We believe it has the potential to initiate and continue wound healing in this patient population,” said Jeff Jonas, MD, president of Shire Regenerative Medicine. “We are committed to developing regenerative medicine solutions that enable people with life-altering conditions to lead better lives, and are encouraged by the fast track and orphan drug designations we have received to further develop this potential therapy for people, most often young children, suffering from this devastating condition.”

Shire is also developing an intravenous protein replacement therapy for the treatment of dystrophic EB, which the company’s Human Genetic Therapies business recently acquired from Lotus Tissue Repair, Inc. Initiation of this pivotal trial of ABH001 for patients with EB further demonstrates Shire’s commitment to developing a portfolio of products targeted toward patients who suffer from this disease.

ABH001 is comprised of allogenic neonatal dermal fibroblasts seeded on a poly(glycolide-co-L-lactide) scaffold, and is currently approved and marketed in the United States as a Class III medical device under the trade name Dermagraft for the treatment of diabetic foot ulcers.

Epidermolysis Bullosa is a family of genetic skin fragility disorders, primarily clinically characterized by blistering of the skin in response to friction or minor trauma. Although genetically and phenotypically heterogeneous, the common factor in all EB patients is the near constant presence of skin erosions and wounds. Severe forms of EB cause patients to live with constant pain and scarring, and may be fatal.

ABH001 is a tissue-engineered, human fibroblast-derived dermal substitute generated by culturing human neonatal dermal fibroblasts onto a bioabsorbable polyglactin (PGLLA) mesh scaffold. The fibroblasts, which are grown onto the PGLLA mesh, secrete dermal collagen, other extracellular matrix proteins, growth factors, and cytokines, creating a three-dimensional human tissue containing metabolically active living cells. The final product consists of a well-developed dermal matrix and evenly dispersed neonatal dermal fibroblasts.

Dermagraft is indicated for use in the treatment of full-thickness diabetic foot ulcers greater than six weeks duration, which extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure. Dermagraft should be used in conjunction with standard wound care regimens and in patients that have adequate blood supply to the involved foot. Dermagraft is contraindicated for use in ulcers that have signs of clinical infection or in ulcers with sinus tracts. Dermagraft is contraindicated in patients with known hypersensitivity to bovine products, as it may contain trace amounts of bovine proteins from the manufacturing medium and storage solution.