Discovery and development of avotermin (recombinant human transforming growth factor beta 3): a new class of prophylactic therapeutic for the improvement of scarring.

Scarring in the skin following surgery or trauma may be associated with adverse aesthetic, functional, growth and psychological effects, such that both physicians and patients regard it as important to minimize the appearance of scars. The prophylactic improvement of cutaneous scar appearance represents a significant opportunity to improve the well-being of patients. Human recombinant transforming growth factor beta 3 (avotermin) is the first in a new class of therapeutic agents to address this medical need.

Effects of avotermin (transforming growth factor β3) in a clinically relevant pig model of long, full-thickness incisional wounds.

Background: The pig is an accepted species for evaluating the safety of molecules in dermal wound healing indications; however, the sizes of wounds assessed have not always been comparable to large incisions encountered clinically.

Objective: To develop a clinically relevant model of incisional wounding in the Göttingen minipig for assessing the safety and tolerance of compounds in development to improve scarring.

Methods: Intradermal avotermin (recombinant transforming growth factor β3 [TGFβ3]) up to 6,000 ng/100μL was administered twice to 20 cm full-thickness incisions.

Therapies with emerging evidence of efficacy: avotermin for the improvement of scarring.

Many patients are dissatisfied with scars on both visible and non-visible body sites and would value any opportunity to improve or minimise scarring following surgery. Approximately 44 million procedures in the US and 42 million procedures in the EU per annum could benefit from scar reduction therapy. A wide range of non-invasive and invasive techniques have been used in an attempt to improve scarring although robust, prospective clinical trials to support the efficacy of these therapies are lacking.

Therapeutic improvement of scarring: mechanisms of scarless and scar-forming healing and approaches to the discovery of new treatments.

Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in loss of function, restriction of tissue movement and adverse psychological effects. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have typically not translated to the development of effective therapeutic approaches for scar management. Existing treatments are unreliable and unpredictable and there are no prescription drugs for the prevention or treatment of dermal scarring.

Avotermin for the improvement of scar appearance: a new pharmaceutical in a new therapeutic area.

Disfiguring scarring in the skin is an area of high medical need. Current treatments for scarring have variable or limited effectiveness and have typically not been evaluated in randomized, controlled, double-blind clinical trials. The prophylactic improvement in scar appearance, through administration of agents around the time of injury, represents a new therapeutic approach for which there are currently no registered pharmaceuticals.

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

Background: Research into mechanisms of skin scarring identified transforming growth factor beta3 (TGFbeta3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFbeta3).

Methods: In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0.

New therapeutics for the prevention and reduction of scarring.

Published literature shows that both physicians and patients are highly concerned about scarring and value even small improvements in scar appearance. Both severe and relatively minor scars can have a significant psychological impact on patients, irrespective of whether or not they are hidden by clothing. There is no universal standard of care for scarring and, currently, no marketed pharmaceuticals for the prophylactic reduction of scarring.

Prevention and reduction of scarring in the skin by Transforming Growth Factor beta 3 (TGFbeta3): from laboratory discovery to clinical pharmaceutical.

Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in adverse aesthetics, loss of function, restriction of tissue movement and/or growth and adverse psychological effects. Current treatments are empirical and unpredictable, and there are no prescription drugs for the prevention or treatment of dermal scarring. We have investigated the cellular and molecular differences between scar-free healing in embryonic wounds and scar-forming healing in adult wounds.