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Innovative Russian Drug Receives High Assessment from Specialists

On June 30, 2012, at the 23rd Annual Conference of the Russian Society of Angiologists and Vascular Surgeons in St. Petersburg, a presentation was made of Russia’s first gene-therapy drug Neovasculgen®, developed by the Russian biotech company the Human Stem Cells Institute (HSCI). The presentation was part of the launch program for the product in Russia.

Neovasculgen® is designed to treat Peripheral Arterial Disease (PAD), including Critical Limb Ischemia (CLI), caused by atherosclerosis (a thickening of artery walls and subsequent reduction of blood flow). While there are no official statistics on PAD in Russia, according to HSCI’s estimates no less than 1.5 million citizens suffer from this ailment. In Russia each year approximately 144,000 patients are diagnosed with CLI and 30,000-40,000 patients undergo amputations.

More than 300 leading Russian and foreign specialists in vascular surgery attended the conference’s symposium on Topical Issues Concerning the Treatment of Patients with Inoperable Lower Limb Occlusion: New Approaches, New Possibilities.

Valery Arakelyan, Professor, M.D., Ph.D., Head of Vascular Surgery and Angiology at the Bakoulev Scientific Center for Cardiovascular Surgery of the Russian Academy of Medical Sciences, made a presentation on “Unresolved Problems in the Treatment of Patients with Lower Limb Occlusion.” He noted that the epidemiology of PAD is quite troubling. According to foreign sources, in the Unites States and Western Europe 27 million people have been diagnosed with this disease. In the United States alone more than 28,000 emergency operations are carried out each year as a result of this ailment. In terms of the mortality of patients diagnosed today with PAD, in 15 years’ time only little more than 30% will remain alive and of the patients diagnosed with CLI – only little over 8% will survive over this period. Treatment tactics can be divided into two categories depending on whether surgical intervention is an option. In the case when reconstructive surgery on the arteries is not possible and the patient is in stable condition, nonsurgical treatment is used. In the worst case situations, and when gangrene develops, the limb is amputated.

The TransAtlantic InterSociety Consensus guidelines (TASC II) on the diagnosis and treatment of PAD indicate that it is highly likely that there is no alternative to reconstructive surgery. However, medicinal analogues are prescribed to treat the disease when it is in the IIb stage. This treatment entails the application of three groups of drugs – two kinds of prostaglandins and the use of VEGF. TASC II highlights in particular the first positive results from the use of VEGF. “In my opinion, the inclusion of the new domestically made drug Neovasculgen in the State Registry of Medications is very important for our country and for patients suffering from Peripheral Arterial Disease,” noted Dr. Valery Arakelyan. “The long-term results of reconstructive surgery described in Western and Russian literature leave much to be desired. I would like to point out that among patients who underwent endovascular surgery, in 8-10 years’ time positive results were seen in only 30-40% of the cases while for 70% of the patients the results were negative. We are closely following the randomized controlled studies which are now being carried out on the use of the endothelial growth factor and expect that the results in medical practice will lead to new approaches for treatment of this serious disease.”

Roman Deev, HSCI’s Chief Scientific Officer, presenting a report on “Modern Biopharmaceutical Approaches to Overcome Unresolved Problems in Vascular Surgery,” noted that the concept of therapeutic angiogenesis was only recently formulated. This concept implies the use of a new biopharmaceutical treatment strategy for improving perfusion of ischemic tissues though mechanisms aimed at developing the microvascular structure. Therapeutic angiogenesis is developing along three main vectors: the use of post-genome, cell-based and gene technologies. At present approximately 20 documented clinical trials have been completed worldwide, testing various prototypes of gene-therapy drugs. These are prototype drugs because only one has made it to the stage of clinical use – Neovasculgen. The medical community has shown great concern over the possibility of tumor induction with the use of drugs based on gene therapy. Studies of gene-therapy drugs for therapeutic angiogenesis have been conducted for approximately 20 years, and their results have convincingly demonstrated that no oncological side-effects have been observed with the use of such drugs. In terms of efficacy, studies have shown that the most effective is the VEGF165 gene, which is a component of Neovasculgen.

As of 2012, there are currently more than 1500 documented clinical trials underway in the realm of gene therapy worldwide. It is pleasing to note that such studies are being done also in Russia. In terms of the nosological structure, clinical trials related to treatment of cardiovascular diseases are second only to studies related to treatment of oncological ailments.

Roman Deev expressed his gratitude to the treatment centers where the clinical trials of Neovasculgen were held and noted: “The Human Stem Cells Institute works and will continue to work with the leading specialists in vascular surgery and continues to study more targeted applications for the drug.” 

Dmitry Voronov, Senior Research Fellow and Vascular Surgeon at the Petrovsky National Research Center of Surgery of the Russian Academy of Medical Sciences, made a presentation on “Clinical Results of the Application of Gene-Engineering Technologies of the Induction of Angiogenesis in the Comprehensive Treatment of Patients with Chronic Ischemia of the Lower Limbs.” Dmitry Voronov noted that “the effectiveness of therapeutic angiogenesis is unquestionable. The methods discussed today have absolutely been proven to induce the formation of new blood vessels, increase microvasculatory blood flow and evoke vascularization of ischemic tissues, which means improving the condition of patients diagnosed with Peripheral Arterial Disease. We believe that the combined use of reconstructive vascular surgery with subsequent stimulation of angiogenesis is not only an interesting but also an effective approach.”

Ilya Staroverov, M.D., Ph.D, Yaroslavl State Medical Academy, in his presentation on “Long-Term Results of Treatment of Patients with Peripheral Arterial Disease with Gene-Therapy Drug,” said that according to the results of studies carried out at the Yaroslavl Regional Hospital “we came to the conclusion that Neovasculgen has shown itself to be effective as a part of the comprehensive treatment of Peripheral Arterial Disease, having a rather prolonged effect, which has been confirmed by observation of patients over a two-year period. Such an innovative approach is indispensable when we cannot help the patients using traditional methods.”

Roman Kalinin, Rector, Ryazan State Pavlov Medical University, M.D., Professor of the Department of Angiology, Vascular and Operative Surgery and Topographical Anatomy, delivered a report on “Innovations in Vascular Surgery: Results of the Use of the Gene-Therapy Drug Neovasculgen.” Roman Kalinin noted: “Of principle importance and necessity is the existence of a means of nonsurgical treatment making it possible to expand the prospects for assisting not only inoperable patients but also those who for some reason or another decline to undergo operation and also providing the opportunity to prevent the development of chronic and acute ischemia. In our studies we analyzed not only the efficacy of the drug but also its safety, as this is the first thing a surgeon thinks about when deciding whether to use innovative methods. According to study results, we saw improvement in the condition of 94% of the patients and believe that therapy using the drug Neovasculgen provides anatomic and clinical success and an absence of complications.” In his presentation, Professor Kalinin also demonstrated the results of an angiography, convincingly confirming the development of collateral blood vessels following the injection of the drug. “The 20th century was the century of vascular surgery. Now we are continuing progress toward new technologies. The emergence of drugs with this mechanism of action incites much optimism among specialists,” he noted.

Alexander Gavrilenko, corresponding member of the Russian Academy of Medical Sciences and one of the pioneers in therapeutic angiogenesis, emphasized, “The gene-therapy method under consideration at this session is safe, and it works. Today this fact is not questioned at the leading clinics around the world. The application of gene-engineering technologies opens new horizons. This method should be used and we must have it available, as it allows for the expansion of the surgeons arsenal with hopelessly ailing patients.”

Valery Arakelyan drew the attention of participants of the symposium to the fact that “unfortunately surgery cannot do everything. According to TASC II recommendations if the patient is operable then this is done first. However, with one-fourth of patients ischemia develops rapidly and they might not be able to undergo surgery. The endothelial growth factor is recommended by TASC II as a method which produces good results. We all need to make note of this. We should be receptive to the signs that there are new methods for treatment which should not be ignored; they should be studied and used.”

Anatoly Pokrovsky, Academician of the Russian Academy of Medical Sciences, President of the Russian Society of Angiologists and Vascular Surgeons, Head of Vascular Surgery at the Vishnevsky Institute of Surgery, in his concluding remarks at the symposium said, “There are a great number of people suffering from vascular ailments in the limbs, who have chronic ischemia. Realistically surgery cannot address the needs of all patients with this disease. We must have at our disposal drugs for nonsurgical treatment. At present this arsenal is small. In reality we have only two or three drugs. But this is not enough to treat all patients. There should be a search for drugs that improve the patient’s condition and circulation in the limbs. Neovasculgen improves the condition of patients, and we must keep this in mind and continue studies and observations of this drug’s effect. We have all the reasons to do so.”

Artur Isaev, General Director of HSCI, noted, “It took more than 11 years to develop Neovasculgen and bring it to market. Over this period we have done a lot of work. The first studies of the drug were carried out in 2000-2001. Over the past four years clinical safety and efficacy trials were carried out in accordance with the protocols confirmed by Russia’s regulatory body Roszdravnadzor. The body of proof received had fully satisfied experts of the Russian Ministry of Healthcare and Social Development, and, despite difficulties related to the complicated Russian regulatory system, HSCI succeeded in obtaining market authorization for the drug. I believe that the registration of a first-in-class drug with a gene-therapy mechanism of action is a global achievement not only for HSCI but for Russia, opening a path to new methods of treatment in other areas as well, such as inherited diseases and cancer.”

HSCI received marketing authorization for Neovasculgen® in December 2011. The Ministry of Healthcare and Social Development decided to include the drug in the State Registry of Medications based on findings on the drug’s efficacy and safety reached during the pre-clinical studies and clinical trials carried. The therapeutic effect following a treatment course of Neovasculgen® continues for at least one year; however, new data indicates that for the vast majority of patients the results attained remain stable for up to two years. The observation of patients participating in the clinical trials over the course of two years concluded in November 2011 and the results will be published soon. It is suggested that the drug’s mechanism of action can provide an even longer effect.

20 July 2012