The drug avotermin (Juvista) could provide accelerated and permanent improvement in scarring following injuries. The findings are reported in an Article in this week's Lancet, written by Professor Mark Ferguson, University of Manchester, UK, and Renovo, Manchester, UK, and colleagues.
Skin is the most frequently injured tissue, and millions of people worldwide acquire scars every year. Two decades of research into the mechanisms of skin scarring has identified transforming-growth factor β3 (TGFβ3) as a potential antiscarring therapy. It works through early induction of specific signaling and cellular processes, which lead to improved structure of the healing skin and wounds. In this Article, the authors report on three randomised controlled phase I/II proof-of-concept and dose-finding trials that aimed to assess the effect of prophylactic administration of avotermin (Human Recombinant TGFβ3) on skin scarring.
The patients (all healthy, mostly men*) randomised to avotermin had the drug (at concentrations ranging from 0.25 to 500 ng / 100 µL) administered before wounding and again 24 hours later to both margins of 1cm incisions that went all the way through the skin of the upper inner arm to the depth of the underlying muscle. Identical wounds on the other arm were randomised to placebo and standard wound care. The primary endpoints were visual assessment of scar appearance at six months and 12 months after wounding in two studies, and from week six to month seven after wounding in the third. Investigators, participants, and scar assessors were all unaware of which treatment had been assigned to which wound.
The researchers found that, in two studies, avotermin 50 ng /100 µL per linear cm wound margin significantly improved outcome on a visual 100-point scale by an average of five points at month six and eight points by month 12. In the third study, avotermin significantly improved total scar scores at all concentrations versus placebo (from 15 points at the 5ng dose up to 64 points for the 500ng dose). 60% of scars treated with avotermin 50 ng /100 µL per linear cm showed 25% or less abnormal orientation of the collagen fibres in the skin, versus 33% of scars treated with placebo, demonstrating an improvement in the structure of the healed skin with the avotermin treatment.
The authors conclude: "Results of these phase I/II studies show that avotermin is a new class of prophylactic medicine promoting the regeneration of healthy skin and improving scar appearance compared with controls. With low doses injected locally around the time of surgery, avotermin is a well tolerated and convenient treatment. These studies suggest that avotermin has potential to provide an accelerated and permanent improvement in scarring."
In an accompanying Comment, Dr Edward E Tredget and Dr Jie Ding, University of Alberta, Canada, say: "With successful completion of these phase I/II studies, the opportunity to extend the use of TGFβ3 into more clinically significant scar models and to develop new methods of delivery of the TGFβ3 protein, or its gene, has been offered by this promising initial work. With these investigations, Ferguson and colleagues provide substantial optimism for new solutions to difficult fibrotic disorders in the future."
Professor Mark Ferguson, University of Manchester, UK, and Renovo, Manchester, UK T) +44 (0) 161 276 7121 / +44 (0) 7710 381 361 E) mark.ferguson@renovo.com
Dr Edward E Tredget, University of Alberta, Canada T) +1 (780) 407-6979 E) etredget@ualberta.ca
For full Article and Comment, see: http://press.thelancet.com/scarring.pdf
And for high resolution images from the Article, (which you are free to use in your publications, please credit The Lancet), see: http://press.thelancet.com/1270.JPG / http://press.thelancet.com/1272.JPG
Notes to editors: *The study populations were predominantly male, because of inclusion and exclusion criteria designed to avoid inclusion of women of childbearing potential into these first-in-man studies
Journal
The Lancet