Ark Holds Positive End of Phase II Meeting with FDA on Trinam(R) Gene Therapy
- Category: DNA RNA and Cells
- Published on Friday, 12 January 2007 02:00
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LONDON, UK | Jan 11, 2007 | Ark Therapeutics Group plc ('Ark') today announces that it has held a positive 'end of Phase II' meeting with the US Food and Drug Administration ('FDA') regarding Trinam(R), its novel gene therapy to prevent blood vessels blocking in kidney dialysis patients who have undergone vascular access graft surgery.
Key points to emerge from the meeting were that the FDA has agreed that the data from the Phase II trial, reported by Ark in August 2006, are sufficient to allow progression to Phase III and a single Phase III trial will be acceptable for the basis of a marketing approval. Furthermore, the FDA has offered Special Protocol Assessment (SPA) for the single pivotal Phase III study for Trinam(R).
The SPA procedure allows Ark to work directly with the FDA to ensure the design of the trial, the definitive clinical objectives and data analyses are optimised to support regulatory approval.
The Phase III study is being planned as a multi-centre, randomised, controlled trial of up to 250 patients in which the efficacy and safety of Trinam(R) 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(R) 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. The primary endpoint of the trial will be the time to graft failure.
Ark reported the preliminary results of the ongoing, open-label, standard-care controlled Phase II trial in August, with the new data from the trial showing that the access grafts of low dose patients remained functional for dialysis on average over five times longer (17.8 months) than control patients in the trial (3.3 months). At that time, in the high dose group, recruited after the low dose group, all patients with successful graft implants had open grafts with patency averaging 8 months. For the primary end point of safety, no quantifiable systemic distribution of Trinam(R) was found in either of the high or low dose groups and the product is well tolerated. No serious side effects were exhibited other than those consistent with the nature of the operation and condition.
As part of the overall Trinam(R) programme, Ark also announces today that, after consultation with the FDA, it intends to undertake a small pre-clinical study on Trinam(R), investigating biodistribution in an 'end-to-side' procedure for surgical placement of the graft. If the results of this trial are in line with expectations, it will allow the Phase III trial to include this procedure alongside the 'end-to-end' placement procedure. Pending SPA agreement, the Phase III study is expected to commence around mid-2007 and to last for approximately 18 months.
Commenting on today's announcement, Dr Nigel Parker, Chief Executive of Ark, said:
'The FDA's positive response to the next stage of Trinam(R)'s development, particularly its offer of Special Protocol Assessment, confirms our belief in the future of this product. We have very encouraging Phase II data on the clinical effectiveness of Trinam(R) and believe that Trinam(R) may have a valuable role to play in the treatment of kidney failure patients where the problem of vascular access blocking is identified in the US Healthy People 2010 Framework as one of the key medical issues to be resolved. This outcome is in line with our budgeted plan and we look forward to giving a further update after receiving Special Protocol Assessment and to the commencement of the Phase III study.'
For further information:
Ark Therapeutics Group plc Tel: + 44 (0)20 7388 7722
Dr Nigel Parker, CEO
Martyn Williams, CFO
Financial Dynamics Tel: +44 (0)20 7831 3113
Notes to Editors
Ark Therapeutics Group plc
About Trinam(R) and Renal Failure
Patients in renal failure depend on effective vascular access for haemodialysis, which removes blood from the body, cleans it and returns it, usually three times a week. Without dialysis these patients would die. A common method of gaining access to the circulatory system is via an artificial blood vessel (vascular access graft) surgically implanted between an artery and a vein in the forearm. However, in a majority of patients, the grafts become blocked due to overgrowth of muscle tissue inside the blood vessel (intimal hyperplasia) and this requires further complex surgery to allow dialysis to take place.
Trinam(R) 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.
In the US and Europe, there are an estimated 150,000 cases each year where Trinam(R) might be used. In patients fitted with haemodialysis access grafts, up to 60% of the grafts block within a year of being inserted and repeat surgery shows more rapid failure rates(1). There are currently no approved drug therapies to reduce failure rates of haemodialysis access graft procedures. The clinical need for an effective treatment is such that the National Institutes of Health in the US has highlighted it as a priority requiring a solution in the Healthy People Directive 2010.
(1) Reference: Rosas SE et al, Determinants of successful synthetic haemodialysis vascular access graft placement. J. Vasc. Surg. 2003;37:1036-42.
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 two marketed devices, Kerraboot(R), and Flaminal(R), and three further lead pharmaceutical products in late stage clinical development: CereproTM, VitorTM, and Trinam(R), the Group is transitioning from an R&D company to a commercial, revenue generating business.
Ark's existing 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.
SOURCE: Ark Therapeutics Group plc