Avotermin Could Give Accelerated And Permanent Improvement In Scarring

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 ??3 (TGF??3) 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 TGF??3) 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 TGF??3 into more clinically significant scar models and to develop new methods of delivery of the TGF??3 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."


"Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies"

Mark W J Ferguson, Jonathan Duncan, Jeremy Bond, James Bush, Piyush Durani, Karen So, Lisa Taylor, Jonquille Chantrey, Tracey Mason,
Gaynor James, Hugh Laverty, Nick L Occleston, Abdul Sattar, Anna Ludlow, Sharon O'Kane

Lancet 2009; 373: 1264-74


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Tony Kirby

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The Lancet

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