BioWorld International Correspondent

LONDON - Renovo plc announced a mixed bag of results in two Phase II trials of its anti-scarring product Juvista, reporting that it failed to meet the primary endpoint in breast enlargement surgery, but was effective in a scar revision trial.

Despite the failure, CEO Mark Ferguson said he is confident of getting a broad anti-scarring claim on the label. The company now will consult with European regulators on how to design the Phase III program to achieve that, and those trials will go ahead as planned in the second half of this year.

"The large scar reduction market remains accessible," Ferguson told a meeting called to discuss the results.

Renovo also will be consulting its partner Shire Pharmaceuticals plc, which licensed rights to Juvista in all markets outside Europe in a $825 million deal signed in June 2007.

In its bid to secure the broad anti-scarring label, Manchester, UK-based Renovo has mounted an extensive Phase II program of Juvista, human recombinant TGF-beta3. It now has reported nine trials, of which seven have been positive, with two more in progress. The second failed trial, which reported in December, was in healing following mole removal.

Ferguson noted also that the large Phase II will be very important to the design of the Phase III trials. "The whole purpose of the large Phase II was to provide appropriate learning before Phase III, optimize drug efficacy and learn about trial design."

He added that the reason for the failure in breast augmentation appears to be straightforward. Subjects were given a single injection at the time of surgery, while in the successful scar revision trial, subjects were injected with Juvista at the wound margins at the time of surgery, and again 24 hours later. In the light of that, the company is considering changes to an ongoing single-dose trial in breast reduction surgery.

In the scar revision trial (as in other of the Phase II trials), patients acted as their own control. One end of the scar is injected with Juvista after revision surgery, the other with placebo, with an untreated gap in between. Ferguson showed time-lapse slides of one subject from immediately postsurgery to nine months postsurgery that clearly showed the Juvista-treated part of the wound to have healed with far less scarring.

Ferguson said the extensive Phase II program has been very successful, demonstrating among other features that Juvista works both in patients and in people having elective plastic surgery, in young and old skin of any color, on any part of the body, and in males and females. In addition, all the Phase II trials were conducted with drug substance manufactured for Phase III trials at a commercial scale.

Ferguson expects to have to conduct at least three Phase III trials to get approval in Europe. "It's not clarified if these will all be in the same indication. We now need to discuss what we do in Phase III and what in Phase IV."

While it will not want the Phase III European trials to run for too long, Renovo has plenty of cash, boasting £93.8 million (US$186 million) in the bank as of Dec. 31. Shire is due to pay for the U.S. clinical program.