Renovo, Shire Developing Anti-Scar Drug

The resilience of alligator embryos could hold the clue to reducing scars in people after surgery.

A British company, Renovo Group PLC, is developing an experimental injectable drug designed to prevent or reduce scarring. The drug, Juvista, originated in experiments conducted by Renovo's founder a quarter century ago in animal embryos. Renovo and its partner, Shire PLC, believe Juvista has blockbuster potential if patient trials are successful and it receives regulatory approval.

Mark Ferguson, now chief executive of Renovo, was researching the birth defect known as cleft palate, in which there's a gap in the upper lip and mouth. As part of his research, he tried to surgically create a cleft palate in alligator embryos. But when the altered alligators were born, the wounds had healed.

The puzzling outcome led Ferguson to find that high levels of a substance called transforming growth factor beta-3, or TGF beta-3, were present in embryonic skin. In contrast, the substance is present in low levels in adult wounds that scar. Ferguson guessed that injecting a drug based on TFG beta-3 could help prevent or minimize adult scars.

Ferguson conducted research on such a drug at the University of Manchester and founded Renovo in 2000. Juvista, a human recombinant version of TGF beta-3, is injected into the skin surrounding a wound at the time of surgery. It's not designed to treat existing scars, though Renovo is studying its use in scar revision, which is a surgical procedure that tries to improve the appearance of an existing scar.

"This is a regenerative drug," Ferguson, who remains a professor at University of Manchester, said during a conference call with analysts last week. "You're trying to regenerate the normal skin."

There's no guarantee Juvista will ultimately work. Although Renovo says early studies have shown promise, the data haven't yet been published in any peer-reviewed medical journals. Renovo still needs to conduct a large patient study to generate data on safety and effectiveness that would be acceptable to the U.S. Food and Drug Administration and other regulators.

Renovo plans to begin the larger studies in Europe next year, possibly in scar revision or breast augmentation procedures. Juvista is unlikely to reach the market before early next decade.

Renovo is now testing Juvista's potential in about a dozen patient trials. In some cases, healthy volunteers agreed to undergo small incisions under both arms. Juvista is used in one wound while a dummy drug, or placebo, is injected into the other, and the results are compared. Juvista also is being evaluated in actual procedures such as varicose-vein removal, breast augmentation and mole removal.

So far, Renovo says the data are largely positive, but with one recent exception. Last week Renovo disclosed that a study of Juvista in people having moles removed didn't significantly improve scar appearance versus placebo. Renovo attributed the failure to a flawed study design, rather than to problems with the drug itself.

In six other studies, however, Juvista met the primary goals of improving scar appearances. In photos provided by the company, some scars treated with Juvista appear narrower and less red than those treated with a fake drug, and some are barely visible.

Juvista hasn't improved every scar on which it's tested. In one study, Juvista improved appearance of 62 percent of scars versus placebo, but 38 percent had no improvement.

Side effects appear minimal, according to the company. Renovo said the most common adverse events were headache and flu-like symptoms, but any side effects thought to be related to treatment were at a similar rate between Juvista and placebo. It's administered in relatively low doses and only at the wound site, not systemically throughout the body.

The market opportunity for an anti-scarring drug could be big. There are currently no prescription drugs approved for preventing scarring, though there are topical treatments designed to promote better healing of scars. Renovo has predicted a U.S. market of $4 billion for such a drug. The forecast is based on a price of $300 to $400 per procedure, said spokesman Simon Bielecki.

More conservatively, Nomura Code Securities analyst Samir Devani has predicted peak annual sales of $1.2 billion for Juvista, following a product launch of either late 2011 or in 2012. Devani based his assumption on a price of $200 per patient.

In June, Renovo sold the non-European Union marketing rights for Juvista to Shire, while Renovo will retain marketing rights for EU member states. Renovo would book European sales while Shire would record sales in other regions.

"This is a completely untapped market, where Renovo and Shire have a significant lead over the competition," Devani said.

Devani sees the drug being used primarily in cosmetic surgery and less so in other types of surgery.