Prominent scarring of the skin after injuries, burns or surgery remains an important and unresolved problem in medicine. Currently, there is no single drug treatment that has been shown to be effective to prevent scarring, although many treatments are used empirically without being evaluated in clinical trials. Transforming growth factor β3 (TGFβ3), is synthesized predominantly by keratinocytes and fibroblasts, and has potential anti-scarring properties as it has been observed in embryos. Avotermin (Juvista, Renovo, UK) is a human recombinant TGFβ3 that has been tried for these purposes in animal models, where it has shown the potential to provide accelerated improvement in scarring.

In a recent report published in the April 10 issue of The Lancet, a group of English investigators performed 3 double-blind, placebo-controlled studies, where they compared the preventive administration of avotermin with placebo or standard wound care in healthy volunteers aged 18 to 85 years. Participants received 1-cm incisions on each arm, and were randomized to receive an intradermal injection of either placebo or 0.25 to 500 ng/100 µL per linear centimeter of wound margin of avotermin. The scars were assessed visually at 6 months and 12 months in the first 2 studies, and from week 6 to month 7 in the third. In all the 3 trials there was a significant improvement of the scars treated with avotermin when compared with placebo. In addition, the histological studies performed demonstrated a better orientation of collagen fibers (more closely mimicking normal skin) in the avotermin treated scars. There were no treatment-related serious adverse events in these trials. This series of studies show that avotermin can be a promising new treatment that can help in the improvement of scar appearance. Studies addressing the potential of this new class of drugs in the treatment of hypertrophic scars and keloids, or fibrotic disorders such as scleroderma should be done in the future.

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

Ferguson MWJ, et al.

Lancet 2009; 373: 1264–74.

Background: Research into mechanisms of skin scarring identifi ed transforming growth factor β3 (TGFβ3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFβ3).

Methods: In three double-blind, placebo-controlled studies, intradermal avotermin concentrations ranging
from 0•25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00847925, NCT00847795, and NCT00629811.

Results: In two studies, avotermin 50 ng/100 μL per linear cm signifi cantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range –2 to 14; p=0•001) at month 6 and 8 mm (–29 to 18; p=0•0230) at month 12. In the third, avotermin signifi cantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14•84 mm [95 % CI 5•5–24•2] at 5 ng/100 μL per linear cm to 64•25 mm [49•4–79•1] at 500 ng/100 μL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 μL per linear cm showed 25% or less abnormal orientation of collagen fi bres in the reticular dermis versus fi ve [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16•12 mm (95% CI 10•61–21•63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing.

Interpretation: Avotermin has potential to provide an accelerated and permanent improvement in scarring.

Funding: Renovo (UK).

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