Renovo - Juvista Safety Studies Following Keloid Excision Concluded Successfully
Renovo Group plc (LSE : RNVO), the biopharmaceutical company developing drugs to reduce scarring, improve wound healing and enhance tissue regeneration, today announces that its Phase I dose ranging clinical trials designed to establish the safety of Juvista® following the surgical excision of bilateral earlobe keloids met all primary safety objectives.
As anticipated in the protocols, the sample size was insufficient to analyse the efficacy data statistically and no conclusions can be drawn at this time.
In line with Renovo’s previously announced development programme, further efficacy trials for Juvista® in additional indications such as primary surgeries, Keloids and trauma are planned to follow the successful completion of the EU Phase III scar revision trials.
Professor Mark WJ Ferguson, CEO, Renovo Group plc commented “It was important to establish the safety of Juvista® when given to patients who develop keloids, as one can not necessarily predict which patients will go on to develop them. This series of safety trials achieved the primary objective across a range of Juvista® doses and provided valuable new information on the natural history of keloid scar development to inform future trial design. The main Juvista® Phase III programme in disfiguring scars remains on track as a potential first-in-class pharmaceutical for the prevention and reduction of scarring following scar revision surgery. We look forward to the results of our fully recruited EU Phase III trial in H1 2011 and an efficacy trial of a new single dose (paediatric) formulation towards the end of 2010”.
For further information please contact:
Prof Mark Ferguson, CEO +44 (0) 161 276 7121
David Blain, CFO +44 (0) 161 276 7113
Tim Anderson / Lisa Baderoon +44 (0) 20 7466 5000
Further trial information
Juvista® is in Phase III of clinical development for the prophylactic improvement of the appearance of disfiguring scars following scar revision surgery. To date patients with keloid scars, which are believed by many experts to be a distinct disorder compared to normal or hypertrophic scars, have been excluded from the Juvista® clinical trial programme as safety in this separate indication had not been established. Accordingly, the purpose of this series of three clinical trials (0064, 0093 and 0107) was to determine the safety of Juvista® when injected (at the time of wound closure and 24 hours later) into the margins of a wound created by the surgical removal of a keloid from the earlobe. Other exploratory endpoints included keloid recurrence, volume and appearance.
Three randomised, placebo-controlled, within patient design trials were conducted in a single site in the USA. In the first two trials, which were of similar design, groups of 10 patients were treated with Juvista® or matched placebo (randomised between ears) with doses which escalated from 50 ng, to 200 ng then to 500 ng/100μl/cm wound margin. Safety was reviewed at 1 month for each cohort before moving to the next dose level. Finally, following a satisfactory review of the safety data at three months at the top dose, a further 20 patients were added to the 500ng dosing group. Patients were followed post surgery for local tolerability and safety (3 months) and general safety (12 months). Local safety included erythema, edema, exudate, itch, burn, pain, dehiscence, bleeding and infection. Notwithstanding the small numbers involved exploratory efficacy measures were made including keloid recurrence, volume (500 ng dose only) and appearance. The protocols specified that the sample size was insufficient to analyse the exploratory data statistically, however the data would be used to facilitate the design of future studies.
The trial met its primary objective in that there were no clinically meaningful differences between Juvista® and placebo treated sites with respect to any of the safety measures in any of the dose groups. Juvista® was well tolerated in the dose range 50 – 500 ng/100 μl/cm with little difference showing in local wound side effects. Adverse events were in line with any outpatient trial, the most common being headache (8%) and Upper Respiratory Tract Infection (6%). Two serious adverse events were reported, neither of which was thought to be related to Juvista® or placebo treatment. Overall in the trial, keloid recurrence rate was lower than expected from the literature and similar between treatment groups. In those keloids that recurred the volumes of the recurred keloid were generally less at 12 months than the original keloid. No conclusions can be made concerning scar appearance: partly due to the small sample size and partly because the trial showed that final scar appearance was influenced by the size of the original keloid, a factor which was not controlled in these trials as they were primarily designed to assess safety.
Keloids are an abnormal form of excessive scarring where the scar tissue grows and expands beyond the margins of the original wound – like a benign tumour, They are more common in dark skinned people, particularly Afro-Caribbeans, and have a genetic (occur in families) basis. They often result from minor injuries or inflammation in the skin e.g. ear piercing, acne or folliculitis, in both men and women. Keloids can grow slowly or rapidly, but rarely regress. They often recur following surgical excision. Keloids behave autonomously, wounds in closely adjacent or bilateral regions of the skin in the same patient may give rise to a keloid in one wound and a normal scar in the other. Fibroblasts cultured from keloids behave and respond differently compared to those from normal skin or scars, supporting a mechanistic hypothesis that keloids arise by localised epigenetic (e.g. methylation) or mutational changes in the fibroblasts. Thus many experts believe that keloids are different from normal/hypertrophic scars and are more like a benign fibrous tumour of the skin or a chronic fibrotic disease. There is currently no diagnostic or prognostic test to predict the risk of an individual/site forming a keloid after surgery/injury, but Renovo has significant patent filings on differences in gene expression profiles, which could form the basis of such diagnostic/prognostic tests.
About Renovo Group plc
Renovo is a biopharmaceutical product company and a leader in the discovery and development of drugs to reduce scarring, improve wound healing and enhance tissue regeneration.
Renovo has a portfolio of products which exploit different novel mechanisms of action to reduce scarring at multiple body sites and improve healing. Renovo’s lead drug for the improvement of scar appearance in the skin, Juvista®, has been generally well tolerated by around 1,500 human subjects. Results from eight double-blind, placebo-controlled trials (1002, 1005, 1007, 0050, 0036, 1009 and 0042), which were designed to explore the safety and efficacy of Juvista® in improving scar appearance, have provided valuable insights into safety and dose response in a variety of clinical settings. These trials met their pre-specified primary endpoints and some exploratory secondary endpoints were also significant. The first European Juvista® Phase III Efficacy trial is fully recruited (over 350 patients from approximately 50 centres in UK, France, Hungary, Germany, Italy, Poland, Spain, Denmark, Latvia and USA) and is due to report results in H1 2011.
Juvista® is licensed to Shire in the USA, Canada and Mexico in a deal worth up to US$830 million in upfront payments, development milestone payments and sales milestone payments plus escalating royalties on net sales. Renovo has already received upfront payments of US$125 million; the next possible milestone payments are US$5 million on commencement by Shire of the first trial for the US, US$25 million on acceptance of filing by the FDA and US$50 – US$150 million on FDA approval, depending on the characteristics of the approved product labelling. Renovo retains rights to Juvista® in all other countries of the world and is exploring partnership opportunities in these countries.
Renovo has previously reported statistically significant efficacy data for Prevascar® in the reduction of scarring in the skin. A new proof of concept clinical study has started in volunteers of African Ancestral Group origin using an improved clinical drug product. Interim data should be available during H1 2011.
Adaprev™ is being developed as a Class III medical device and the first trial for the reduction of tendon adhesions is underway and is due to report results in H2 2011,
Renovo is actively seeking to partner Juvidex® as a cosmetic ingredient for the improvement of skin appearance and acceleration of healing.
As previously guided, the net cash position of Renovo at the time of reporting the first Juvista® EU Phase III trial in H1 2011 is expected to be at least £25 million to £30 million.
For further information on Renovo please visit: www.renovo.com
Forward looking statements:
Information in this announcement is based upon unaudited
management accounts and in addition, certain statements made are
forward looking statements. Such statements are based on current
expectations at the date of this announcement and are subject to a
number of risks and uncertainties that could cause actual events or
results to differ materially from any expected future events or
results referred to in these forward looking statements. We
undertake no obligation to update or revise any forward-looking
statements to reflect any change in our expectations or any change
in events, conditions or circumstances.
Posted: September 2010