Shares in wound-healing regenerative medicines firm Renovo bombed a whopping 74% (and were still falling) within about an hour of the firm announcing that its scar-reducing candidate, Justiva, failed to meet both primary and secondary endpoints in the first EU Phase III trial in scar-revision surgery patients. The Revise™ study evaluated whether injections of the human active recombinant transforming growth factor beta 3 product at the wound margin would benefit the appearance of scars following scar revision surgery.
Over 350 patients were enrolled in the study. Participants were treated using either one of two doses of Justiva or placebo, administered following wound closure and 24 hours later. The primary efficacy endpoint was a photographic-based assessment of scarring 12 months following surgery by an independent panel using the Global Scar Comparison Scale.
Justiva is separately undergoing Phase II program in the U.S. under a development and commercialization agreement with Shire. However, Renovo says it will now have to carry out further analysis of the European Phase III data before deciding on the future of the drug’s development.
“We are extremely surprised and disappointed by the failure of Justiva to meet the Phase III trial primary and secondary endpoints,” remarks Mark Ferguson, Ph.D., Renovo co-founder and CEO. “The board of Renovo will now consider all options open to it to maximize shareholder value.”
Renovo also had plans for Justiva beyond the scar-revision surgery application. The firm has previously stated that if Juvista was to be approved by the EMA for this primary indication, it would also seek to undertake additional Phase IV trials to expand the drug’s use to a wider range of surgical procedures.
As recently as late last year things were looking much better for Justiva. On November 30 Renovo reported the successful outcome of a clinical trial designed to establish the safety and efficacy of a new formulation of the drug intended for use in children. The trial met its primary endpoint, in that single dosing (at the time of wound closure) with Juvista Paediatric statistically significantly improved the appearance of the subsequent scars compared with placebo.
The trial also met a number of secondary endpoints including a confirmation that for the existing adult formulation of Juvista used in the EU Phase III trial, the 500 ng/100 μL/linear cm of wound margin dose produced the most significant improvement in scar appearance.
Shire and Renovo inked their original development and commercialization agreement for Justiva back in 2007, when Renovo received $75 million as an up front payment and another $50 million equity investment by its partner. Following amendments to the deal’s structure in 2010, Shire has development and commercialization rights to Justiva in the U.S., Canada and Mexico.
Renovo’s remaining clinical pipeline is headed by Prevascar, a therapeutic formulation of human recombinant interleukin 10, which has a different mechanism of action as Justiva, but is in development for the same potential market. Clinical data have already demonstrated that Prevascar therapy can help reduce scarring in the skin, Renovo states. The drug is currently undergoing a proof of concept clinical study in surgical skin incisions and excisions in African subjects. Interim data from the study are during the first half of 2011. Next in line in the firm’s pipeline is an injectable mannose 6 phosphate solution, Adaprev, which is in development for the reduction of adhesions following digital tendon injury. In the EU Adaprev has been designated a Class III medical device, and is currently undergoing clinical safety and preliminary performance evaluation. Renovo says discussions with FDA to date indicate that in the U.S. the product would be classified as a drug.