London, UK, 19 April 2010 - Ark Therapeutics Group plc (“Ark” or the “Company”) announces today that the first patient has been treated in the high dose Phase I/IIa trial of adenoviral Vascular Endothelial Growth Factor-D (“VEGF-D”) in patients with peripheral vascular disease (“PVD”). The trial is being undertaken in collaboration with the AI Virtanen Institute in Kuopio, Finland. The programme (EG016) uses the angiogenic VEGF-D gene (Ad-VEGF-D) in Ark’s already successfully developed adenovirus platform.
The patient was given 1 X 1011 viral particles of Ad-VEGF-D into lower leg muscles one day before femoropopliteal artery bypass surgery to restore the main arterial blood flow to the lower leg.
An estimated 300,0001 patients per annum in the US and Europe, have sufficiently impaired blood flow to the lower limbdue to atherosclerosis to require an operation to bypass the blocked blood vessel. Patients with impaired lower limb circulation suffer pain on using their legs (claudication) and in more severe cases, the leg tissue below the blocked artery dies and the leg has to be amputated.
The bypass operation connects a length of healthy blood vessel (taken from elsewhere in the patient’s body, or in some cases a synthetic vessel) between the femoral artery which has good blood flow in the upper leg and the popliteal artery further down the leg to bypass the blocked area. The extent to which this operation is successful relies both on the extent to which the main arterial flow to the lower leg is restored by the bypass operation and the extent to which the patient can re-grow small blood vessels (capillaries) within the leg tissues to carry new blood supply to the areas which have had insufficient blood (ischaemic) for a period of time. Adenoviral mediated VEGF has already been shown by researchers in Finland to significantly increase new capillary growth in the ischaemic leg (AdVEGF–A, n = 54 patients, p<0.03)2
The Phase I/IIa trial is a controlled study in patients with peripheral vascular disease who require femoropopliteal bypass surgery. Initially this programme will compare different doses of VEGF D longform prior to moving to VEGF D?N?C (shortform VEGF-D). Patients will receive either 1x109, 1x1011 viral particles of Ad-VEGF-D, administered by multiple injection into the muscle downstream of the bypass site 1-2 days before the bypass operation, allowing time for the gene to start to work prior to the bypass operation. This pre-bypass treatment approach should allow some advance restoration of the peripheral circulation improving the success of the bypass operation.
The study has been approved by the Finnish National Agency for Medicines (NAM) and is being conducted by Professor Ylä-Herttuala of the AI Virtanen Institute in Kuopio and Dr. Kimmo Mäkinen and Dr. Ismo Vajanto of the Kuopio University Hospital. The study will assess the safety of EG016 as well as providing initial efficacy data.
Prof John Martin Chief Scientific Officer at Ark, commented: “Having already demonstrated success in PVD patients in an earlier study with VEGF-A, we are very optimistic about the success of this trial and we believe our decisions to use VEGF-D and provide EG016 treatment prior to the bypass operation will enhance the overall benefits and success of both treatments to patients.”
Dr Nigel Parker Chief Executive Officer of Ark added: “This enrolment is an important milestone. The progress we continue to make at Ark is facilitated by the use of our established adenoviral platform and a successful co-operation between academia and industry. EG016 is a very exciting product opportunity in a large market with significant unmet clinical need and we look forward to announcing further trial progress as well as news on our other VEGF-D clinical candidates as the year progresses. Our angiogenic gene-based portfolio continues to grow in strength.”
Refs.
1 Company estimates and various sources
2 Increased Vascularity Detected by Digital Subtraction Angiography after VEGF Gene Transfer to Human Lower Limb
Artery: A Randomized, Placebo-Controlled, Double-Blinded Phase II Study. Kimmo Mäkinen, Hannu Manninen, Marja Hedman, Pekka Matsi, Hanna Mussalo,Esko Alhava and Seppo Ylä-Herttuala. Mol Ther 2002:6:127-133
