Juvista Phase 2 Results and Updated Development Plan
JUVISTA® PHASE 2 TRIAL IN SCAR REVISION SURGERY COMPLETED AND OVERALL MET ITS PRIMARY ENDPOINT. AGREED JOINT DEVELOPMENT PLAN FOR JUVISTA® WITH SHIRE<
Renovo Group plc (LSE: RNVO), the biopharmaceutical company developing drugs for the reduction of scarring and acceleration of healing, is pleased to announce that the phase 2 Juvista trial RN1001-1009 (combined groups) in scar revision surgery met its primary endpoint with statistical significance. As previously guided and following positive feedback from the European Medicines Agency (EMEA), Renovo will commence its first European phase 3 efficacy trial in scar revision surgery later in 2008. Renovo also updates the market on the joint development plan for Juvista agreed with Shire.
Scar Revision Phase 2 Trial (RN1001-1009)
• Trial consists of two groups of 30 patients; each group allocated to a different surgical revision technique
• Analysis has now been completed for group 2 and the data for both groups combined
• Primary endpoint for combined group met with statistical significance (p = 0.038)
• Secondary endpoint for combined group of an on the patient assessment by a clinicican also statistically significant in favour of Juvista (p = 0.036)
• Histological analysis (only possible with group 2) indicates a positive Juvista effect in approximately three quarters of the scars assessed
• Design (350 patients) and timelines (commence H2 2008) for the first EU phase 3 trial in scar revision surgery are as previously advised
This trial was a randomised, double-blind, within-patient, placebo controlled Phase 2 study to investigate the safety and efficacy of 200ng per 100L per linear cm of wound margin of Juvista given twice, at the time of surgery following wound closure and 24 hours later.
The study was divided into two groups in order to evaluate the efficacy of Juvista in two different scar revision surgical procedures, both of which involved 30 male and female patients, giving a total trial size of 60 patients. The first group, in which the scar being revised was fully excised in one surgical procedure (most commonly practiced procedure, which will be used exclusively in Renovo’s planned phase 3 clinical trials), reported positively in March 2008. Analysis from the second group, in which a two stage surgical excision procedure was employed, has now been added.
Overall, analysis of the data from the total studied population showed that the trial met its primary endpoint (p=0.038). The primary trial endpoint was photographic evaluation by a lay panel over a time period from week 6 to month 7 post surgery using a visual analogue scale (VAS). Statistical significance was also demonstrated by an on the patient assessment by the investigating clinician at month 7 (LOCF) post surgery using a VAS (p=0.036). A similar assessment by the patient did not demonstrate statistical significance. When analysed in isolation, the data from group 2 were in favour of Juvista, however did not reach statistical significance. The additional data from group 2 do not alter the sample size calculation for the first EU phase 3 efficacy trial.
In group 2, 7 months after dosing, during the second stage of the scar revision procedure, in those patients where the middle section of the scar was excised, the surgeon also removed a small margin of the previously treated Juvista and placebo scars. The microscopic structure of the Juvista and placebo treated scars were compared by Renovo histologists on a blinded, within patient, basis. Approximately three quarters of the 7 month scars assessed from Juvista treated wounds were considered to have a structure more like normal skin compared to the placebo treated scars. This unique data, only available by virtue of the design of the group 2 surgical procedure (two step excision for scar revision) provides further evidence that Juvista treated wounds regenerate a skin structure that is more like normal skin.
The safety and tolerability profile to date, including the latest scar revision trial to report, continues to support Renovo’s plan to progress Juvista into phase 3 development in the EU.
Joint Development Plan agreed with Shire
Following positive feedback from the EMEA, Renovo intends to commence its first European phase 3 efficacy trial in scar revision surgery later this year (as previously advised). This trial will evaluate two doses of Juvista (200ng and 500ng per 100µl per linear cm of wound margin) given twice, following wound closure and 24 hours later, to a total of 350 patients. No further Juvista clinical data are required before commencing this trial.
The data from Renovo’s planned, multi-centre, pivotal EU phase 3 trial, using the EMEA agreed endpoints and protocol, will be used to inform the strategy and design of Shire’s US development plan and to strengthen Juvista’s chances of regulatory and commercial success in the US. Accordingly, Renovo and Shire have agreed the following development plan:
• Renovo will commence its first pivotal EU phase 3 trial in scar revision surgery in H2 2008, as previously advised
• If the outcome from the first EU phase 3 trial in scar revision surgery is suitably positive:
o Shire will request end of phase 2 meetings with the FDA, to agree the US Phase 3 clinical program as well as the non-clinical plan. Given suitable outcomes from these meetings, Shire will look to commence in parallel the phase 3 trials required for filing and registration of Juvista in the US
o Renovo will complete the EU phase 3 programme. Renovo and Shire will aim to execute as much of the phase 3 programme as possible on a collaborative basis such that data can be used for registration purposes in both the US and EU
• Shire and Renovo will cooperate to conduct certain non-clinical studies and manufacturing-related work that will ultimately be required for inclusion in the US and EU regulatory dossiers.
In addition to progressing Juvista, Renovo is continuing to advance the rest of its pipeline. The Company is appropriately funded with £84.5m in cash as at 30 June 2008.
Renovo is on track to report phase 3 efficacy data for Zesteem® in acceleration of healing later in 2008. JuvidexTM is in a phase 2 trial for the acceleration of healing, which will report in H1 2009. Prevascar® reported statistically significant Phase 2 efficacy data for the reduction of scarring in the skin in April 2007 and is currently being considered for other indications.
Professor Mark Ferguson, Chief Executive Officer of Renovo, commented:
“I am pleased that the second part of the Phase 2 scar revision trial has now completed and that the overall result remains positive in favour of Juvista. Our first EU phase 3 efficacy trial in scar revision surgery will commence, as previously guided, in H2 2008 and we have now agreed with Shire a prudent joint development plan for Juvista.”
Angus Russell, Chief Executive Officer of Shire, commented:
“Shire continues to support the development of Juvista and will work with Renovo to ensure the best development programme for the product and outcome for patients. We look forward to seeing the results of Renovo’s first Phase 3 trial and will use these results to shape Shire’s plans for Juvista in the US and our other markets.”
For further information please contact:
Professor Mark Ferguson, Chief Executive Officer
+44 (0) 161 276 7121
Simon Bielecki, Vice President, Communications
+44 (0) 161 276 7142
Mary-Jane Johnson / Tim Anderson / Lisa Baderoon/ Catherine Breen
+44 (0) 20 7466 5000
Trial RN1001-1009 design overview
This trial was a randomised, double-blind, within-subject, placebo controlled Phase 2 study to investigate the safety and scar improvement efficacy of Juvista (INN: Avotermin) in 60 male and female subjects, aged 21 to 78, following scar revision surgery.
The trial was split into two equal groups of 30 patients in order to assess the efficacy of Juvista in two surgical scar revision procedures. The first group (most commonly practiced procedure), where the entire scar was excised and the resultant wound closed in one procedure, reported in March 2008. The second group, where the scar is excised in stages, reports today.
Patients in both groups had scars of at least 5cm in length deemed suitable for surgical revision by excision and direct closure. The area to be revised was split into three segments, consisting of a central section (of at least 3cm) and two end segments of equal length. Scars 9cm or longer were divided into three equal segments.
In the first group 200ng/100L/linear cm of Juvista was administered intradermally at the time of surgery following wound closure and 24 hours later into both margins of one end segment of the wound. The other end segment received placebo at the same times, leaving an untreated (or ‘buffer’) segment in the middle, which received standard care only.
For the second group of patients there was a two step surgical procedure. During the first step the two end segments of the scar were excised and the resultant wounds closed. As with the first group 200ng/100L/linear cm of Juvista was administered intradermally at the time of surgery following wound closure and 24 hours later into both margins of one end segment. The other end segment was treated with placebo in an identical manner and at the same times. Seven months after the original scar revision surgery, the middle segment of the scar and a small section of the previously treated Juvista and placebo ends were surgically excised in a second procedure, the wound closed and treated with standard care only.
For both groups all scars are photographed under standard conditions at week 6 and months 3, 4, 5, 6, 7, 9 and 12. The primary endpoint of the trial is the appearance of the scars as assessed by an independent panel of lay people (to simulate customers) using a visual analogue scale (VAS) over a time period from week 6 to 7 months post surgery.
About Renovo Group plc
Renovo is a biopharmaceutical product company and is the world leader in scar reduction research and the development of drugs to reduce scarring.
Renovo has a portfolio of drugs which exploit different novel mechanisms of action to reduce scarring at multiple body sites and to accelerate healing. Juvista, Renovo’s lead drug for the reduction of scarring in the skin has been safely administered to over 1,500 human subjects and has reported statistical and clinical significance in seven Phase 2 efficacy trials.
Renovo announced in June 2007 that it had signed an exclusive licensing agreement with Shire plc to develop and commercialise Juvista. The agreement covers every country in the world except the European Union, the rights to which have been retained by Renovo. Under the terms of the deal Renovo has already received an initial payment of US$125 million. Contingent on the successful development and commercialisation of Juvista Renovo will be eligible for further payments of up to $700 million together with escalating royalties on sales.
Zesteem, Renovo’s lead drug for the acceleration of wound healing in the skin is currently being investigated in a Phase 3 clinical trial, which is scheduled to report in H2 2008. Prevascar reported statistically significant Phase 2 efficacy data for the reduction of scarring in the skin in April 2007. Juvidex is in a Phase 2 trial for the acceleration of healing.
For further information on Renovo please visit: www.renovo.com