Neovasculgen

The article deals with the use of a genetically engineered drug for stimulation of angiogenesis as a component of combined treatment of complications of ischaemic form of diabetic foot syndrome, showing comparative results of using therapeutic angiogenesis in patients in whom it was impossible to perform operative revascularization of the affected extremity, also providing a detailed description of the methodology of combined treatment of pyonecrotic complications of diabetic foot syndrome. The study included a total of 62 patients with pyonecrotic complications of Wagner grade III-IV diabetic foot syndrome. The patients were divided into two groups. Group One patients after minor amputation on the foot were assigned to receive conventional basic therapy and topical treatment of the foot wound with antiseptics and modern dressings. Group Two patients, besides basic therapy, additionally received combined treatment which was carried out in two stages and included urokinase, sulodexide, and a venotonic agent. Local treatment of the foot wound was performed with the help of two-stage vacuum therapy. Both groups were further subdivided into subgroups A and B. The patients in subgroups B of both groups in order to prevent progression of limb ischaemia were additionally given Neovasculgen, a genetically engineered drug for stimulation of angiogenesis. The patients of subgroups A of both groups did not receive this drug. The immediate results were assessed on the 1st, 7th and 14th days of treatment by the dynamics of changes in subjective symptoms, cytograms of the wound surface, level of partial pressure of oxygen in capillary blood of foot tissues, and the necessity to perform repeated necrectomy. The remote results were evaluated by the dynamics of changes in the pain-free walking distance, maximum distance walked, ankle-brachial index, linear velocity of blood flow through tibial arteries and partial pressure of oxygen in capillary blood of the affected limb at the 6th, 12th and 36th months after the performed treatment, as well as by the limb salvage and patients' survival during 3 years.

The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. pl-VEGF165, a gene therapy drug, was approved in Russia for the treatment of atherosclerotic peripheral arterial disease (PAD) after clinical studies in 2011. The study drug is an original gene construction in which pl-VEGF165 1.2 mg is the active substance.

This postmarketing surveillance study was undertaken to evaluate the safety (identification of uncommon side effects) and efficacy of gene therapy in patients in routine clinical practice.

In total, 210 patients with stage II-III chronic limb ischemia (according to the Fontaine classification modified by AV Pokrovsky) in 33 healthcare facilities in Russia and the Ukraine were enrolled in the study. The control group (n = 60) received conservative therapy without prostaglandins and prostacyclins, and the treatment group (n = 150) received treatment with pl-VEGF165 as two intramuscular injections for a total dose of 2.4 mg. Pain-free walking distance (PWD) (the primary efficacy criterion for Fontaine stages II-III), blood flow linear velocity (BFLV), and ankle-brachial index (ABI) were monitored for 6 months. The safety of pl-VEGF165 gene transfer in terms of the trial protocol was initially evaluated 6 months after the start of the study; adverse events (AEs) and serious adverse events (SAEs) were recorded during both routine visits and unscheduled requests for medical care.

Overall, PWD increased by 177%, from 100.3 ± 6.9 to 277.1 ± 16.2 m (p = 0.0001), in the treatment group, whereas the mean value was unchanged in the control group (p = 0.218). Both BFLV and ABI values increased by 24% (p = 0.0001) in the treatment group but decreased in the control group. The greatest therapeutic effect was observed for stage III disease: PWD increased by 683% (p = 0.0001). No angiogenic therapy-related AEs or side effects were recorded, and target limb salvage was 96 and 97% in the treatment and control groups, respectively. The results obtained in this study are not significantly different from those observed in the phase IIb/III registration clinical study completed in 2011.

pl-VEGF165 intramuscular gene transfer is an effective treatment for moderate to severe claudication due to chronic lower limb ischemia in routine clinical practice. ClinicalTrials.gov identifier: NCT02369809.