PVG.L Regulatory News (PVG)

2 Jun 2008 07:00



Ark Receives Special Protocol Assessment Approval from US FDA 

for Phase III Pivotal Trial of Trinam®

2 June 2008 - Ark Therapeutics Group plc ("Ark" or the "Company") today announces that, following full review by the US Food and Drug Administration (FDA), the application for Special Protocol Assessment (SPA) for its Trinam® Phase III trial, filed in April 2007, has been successful and the FDA has formally given SPA approval. In parallel, the updated Investigative New Drug (IND) application for the trial has also been separately reviewed and approved by the FDA, subject to a requirement for the Company to qualify one product release test relating to potency, prior to enrolling patients.

Trinam® is Ark's novel gene based medicine to prevent blood vessels blocking in kidney dialysis patients who have undergone vascular access graft surgery. Ark will now commence work to start the planned Phase III trial and, in addition, intends to apply to the FDA for Fast Track Designation.

The SPA process allows Ark to work closely with the FDA to ensure the design and conduct of the Phase III development programme, including the definitive clinical objectives and data analyses, are appropriate to support a marketing licence application (BLA). During the course of the SPA review, Ark has conducted a preclinical study and provided extra biodistribution data in an "end-to-side" surgical procedure for placement of the graft. The results were in line with those seen previously, allowing the Phase III trial to include this procedure alongside the existing "end-to-end" placement procedure used in Phase II. 

Trinam® is an adenovirus-mediated VEGF D gene delivered with a novel biodegradeable local delivery device (EG001). The product has already been given Orphan Drug Status in the USA and Europe. The US Recombinant Advisory Committee (RAC) gave approval for a Phase III study in May 2007. US regulatory review for the product comes under the responsibility of the Centre for Biologics Evaluation and Research (CBER), the specialist biologics division of the FDA.

The Phase III study will be a US multi-centre, randomised, controlled trial, in which the efficacy and safety of Trinam® will be investigated in patients with end stage renal disease (ESRD) requiring vascular access for haemodialysis. Patients with ESRD will be randomised to receive either Trinam® 4x1010 viral particles in addition to standard care or standard care alone at the time of surgical placement of a synthetic PTFE graft for vascular access. Primary Unassisted Patency (time to any first intervention) will be the primary regulatory end point and overall patency and a number of other important pre-defined clinical endpoints will also be measured. Safety will be assessed by an independent Data and Safety Monitoring Board (DSMB) against a pre-specified set of stopping rules defined during the SPA. The DSMB will also undertake a 'sample sizing' analysis after 150 patients have been recruited to determine the final trial size. This type of adaptive design is relatively new and assists groundbreaking drugs to ensure robust efficacy data are available to satisfy regulatory requirements as approval standards evolve.

Results from a Phase II open-label, non randomised, standard-care controlled trial of Trinam®, previously reported in March 2007, indicated that the access grafts of patients given the planned dose of Trinam® exhibited almost three times the Primary Unassisted Patency compared with controls. Overall patency data from the Phase II study further showed Trinam® treatment resulted in grafts remaining functional for dialysis, on average, over three times longer than in untreated controls. Trinam® was well tolerated with no quantifiable systemic distribution of the product found and no serious side effects were exhibited other than those consistent with the nature of the operation and condition.

Nigel Parker, CEO of Ark, commented: "This is very good news at the end of what has been an extremely rigorous and detailed review by the FDA and we are delighted to have been successful in achieving SPA for this pioneering gene based medicine. The FDA has provided constructive assistance to ensure we conduct the right study for a medical problem which is identified in the 2010 US Health Peoples Directive as of high clinical need. We will now get on with the test work alongside finalising administration to commence the trial. We look forward to updating the market regarding Trinam®'s progress in due course."

Enquiries

Notes to Editors

Trinam®

Trinam® is a combination of a vascular endothelial growth factor gene in an adenoviral vector (Ad-VEGF-D) and Ark's biodegradable local delivery collagen collar device (EG001). At the end of the access graft surgery procedure, the collar is fitted around the outside of the vein/graft join. The Ad-VEGF-D solution, which reduces the likelihood of blood clots and intimal hyperplasia, is then injected into the space between the wall of the collar and the blood vessel. This unique method of administration of the gene localises its delivery to the target tissue site, maximising efficacy, avoiding systemic distribution and thus minimising the potential for side effects.

Ark Therapeutics Group plc

Ark Therapeutics Group plc is a specialist healthcare group (the "Group") addressing high value areas of unmet medical need within vascular disease, wound care and cancer. These are large and growing markets, where opportunities exist for effective new products to generate significant revenues. With four marketed devices, Kerraboot®, Kerraped®, Flaminal® and Neuropad®, and three further lead pharmaceutical products in late stage clinical development: Cerepro®, Vitor™, and Trinam®, the Group is transitioning from an R&D company to a commercial, revenue generating business.

Ark's own products are sourced from related but largely non-dependent technologies within the Group and have been selected to enable them to be taken through development within the Group's own means and to benefit from Orphan Drug Status and/or Fast Track Designation, as appropriate. This strategy has allowed the Group to retain greater value and greater control of clinical development timelines, and to mitigate the risks of dependency on any one particular programme or development partner. Ark has secured patents or has patent applications pending for all its lead products in principal pharmaceutical markets. 

Ark has its origins in businesses established in the mid-1990s by Professor John Martin and Mr Stephen Barker of University College London and Professor Seppo Yla-Herttuala of the AI Virtanen Institute at the University of Kuopio, Finland, all of whom play leading roles in the Company's research and development programmes. 

Ark's shares were first listed on the London Stock Exchange in March 2004 (AKT.L). 

This announcement includes "forward-looking statements" which include all statements other than statements of historical facts, including, without limitation, those regarding the Group's financial position, business strategy, plans and objectives of management for future operations (including development plans and objectives relating to the Group's products and services), and any statements preceded by, followed by or that include forward-looking terminology such as the words "targets", "believes", "estimates", "expects", "aims", "intends", "will", "can", "may", "anticipates", "would", "should", "could" or similar expressions or the negative thereof. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors beyond the Group's control that could cause the actual results, performance or achievements of the Group to be materially different from future results, performance or achievements expressed or implied by such forward-looking statements. Such forward-looking statements are based on numerous assumptions regarding the Group's present and future business strategies and the environment in which the Group will operate in the future. Among the important factors that could cause the Group's actual results, performance or achievements to differ materially from those in forward-looking statements include those relating to Ark's funding requirements, regulatory approvals, clinical trials, reliance on third parties, intellectual property, key personnel and other factors. These forward-looking statements speak only as at the date of this announcement. The Group expressly disclaims any obligation or undertaking to disseminate any updates or revisions to any forward-looking statements contained in this announcement to reflect any change in the Group's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. As a result of these factors, readers are cautioned not to rely on any forward-looking statement.