BioWorld International Correspondent
LONDON - Renovo Group plc announced the third set of positive Phase II efficacy results for its TGF-beta3 anti-scarring product, Juvista, and said it is preparing to start Phase III in the first half of 2007.
A number of companies are vying to license the drug, and some have submitted terms sheets. Others are conducting due diligence. A deal will be agreed to by April or May 2007 and Renovo is holding back the start of Phase III to allow a future partner to contribute to the protocol design of the large multinational series of scar revision trials the company has lined up, said Mark Ferguson, CEO, at an R&D update meeting in London last week.
"We are of course looking for decent milestones, royalties and up-front payments, but the most important thing for us is significant participation in the marketplace," he said. "It's a huge open market, with huge potential, and that will give the best shareholder return. But we do need to partner, because we can't cover it all."
The latest trial results show that more than 1,000 subjects have received Juvista, with no adverse effects. Ferguson showed photographs comparing healing with and without treatment in the same subject, and Juvista-treated wounds could barely be detected, while the wound that received placebo was visible.
While the earlier trials looked at scarring after wounds were sutured or held together with strips, the latest trial studied open wounds that are left at skin-graft donor sites.
"The trial was statistically significant, and at 12 months the treated sites were improved compared to placebo," Ferguson said. "We've shown that the drug works in an open wound, and it works topically."
The main indication that Manchester, UK-based Renovo is pursuing administering Juvista by injection at the time of surgery. Ferguson said the latest results opened up another market. "Large open wounds are not suitable for injections, but it would be possible to develop a topical formulation. This is a small market, but there is large unmet medical need."
Other ongoing Phase II trials in breast augmentation and mole removal are fully recruited and due to report in 2008, while another in breast reduction started in the first half of 2006. Two trials confirming dose response in commercially manufactured material are in progress, too.
There are an estimated 42 million surgical procedures per year in the U.S. alone. Having carried out all trials to date in the UK, Renovo now is focusing on starting U.S. trials. Recently the company submitted a fast-track application to the FDA for a pilot study of scar prevention following surgery to remove keloid scars. Renovo has three further scar reduction products in clinical development.
Other indications beyond skin are scarring in the eye following glaucoma, cataract or laser eye surgery, adhesions caused by abdominal surgery, vascular restenosis following cardiac bypass surgery, repairing tendon and ligament injuries, and promoting peripheral nerve regrowth following accidents, in which scar tissue prevents cut ends of nerves from growing back.
While Juvista prevents scarring, the product Zesteem accelerates healing. There are a number of advantages of that, Ferguson said: "Patients are more comfortable, they need fewer dressings, and there is less pain and less chance of infection."
Gene expression data showed that while all tagged genes associated with healing are turned on by day seven in treated wounds, they are not all turned on in untreated wounds until day 30, in the same patient.
Zesteem is a novel formulation of estradiol, for which Renovo has use patents. In view of the existing safety data, the company has permission to move straight to Phase III. "We have had formal advice [from the UK regulator MHRA]," Ferguson said. "We need to do two small Phase III trials of a few hundred patients each. The product is being manufactured, and we will start Phase III in 2006."
That could mean Zesteem reaches the market before Juvista. "We will complete Phase III ourselves and partner after approval," Ferguson said. "We are not allergic to partnering before that, but it is not on our active radar. If it happens, it will be opportunistic because we have had a crackerjack offer."
The third product, Juvidex, a formulation of mannose-6-phosphate, inhibits the activation of TGF-beta 1 and TGF-beta 2, while a fourth, Prevascar, is a formulation of interleukin 10.