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Gene Therapy: Neovasculgen

Neovasculgen® is the first-in-class gene therapy drug for the treatment of atherosclerotic Peripheral Arterial Disease (PAD), including Critical Limb Ischemia (CLI).

The drug’s action mechanism – therapeutic angiogenesis – introduces a new approach to the treatment of ischemia (the use of an evolutionarily programmed process of blood vessel creation and growth).

Human Stem Cells Institute (HSCI) received marketing authorization for Neovasculgen® in Russia on December 7, 2011. The Russian Ministry of Healthcare decided to include Neovasculgen® in the State Registry of Medications (RU № LP-000671 of September 28, 2011) based on findings on the drug’s efficacy and safety reached during the pre-clinical studies and clinical trials.

Phase I/IIa clinical trial for Neovasculgen were carried out by HSCI in 2009-2010. In April 2010 HSCI got the Russian regulator's (Roszdravnadzor) official approval to conduct Phase IIb/III of clinical trials, which was completed in 2Q 2011. In mid July 2011 the necessary documentation was submitted to the Russian Ministry of Healthcare and Social Development for obtaining the marketing authorization.

Phase I/IIa clinical trial confirmed Neovasculgen's safety and also provided preliminary conclusions on its efficiency. In Phase IIb/III trials 100 patients were enrolled (75 in the test group who received Neovasculgen treatment (pCMV-vegf 165 intramuscular gene transfer), and 25 in the control group who received standard treatment only). No adverse effects and complications were observed. Pain Free Walking Distance (PWD) was determined to increase by 110% at 6 months that shows statistically significant difference versus the control group. During a 1.5-year additional follow-up period of study, PWD increased in the test group by 167% and 191% at 1 and 2 years after treatment, respectively.

In the end of September 2012, after the drug’s first batches were produced and certified, Neovasculgen® went on sale in Russia through distributors.

Neovasculgen® is sold in the form of lyophilisate to prepare an injection solution; the treatment course comprises 2 sequential injections (i.e. 2 vials) with an interval of 14 days. HSCI manufactures Neovasculgen® by contract basis in Russia: the contractor is the Research Center for Hematology of the Russian Ministry of Healthcare.

Following successful promotional activities, the drug’s sales should account for a substantial portion of HSCI’s consolidated revenue.

In June 2013 Neovasculgen® was included in the National Recommendations for treating patients with Peripheral Arterial Disease.

In order to facilitate patients’ access to Neovasculgen® through federal and regional public medicine subsidy programs (state drug reimbursement), HSCI is actively interacting with the professional medical community and regulatory authorities. One of the first sound results of this work was the inclusion of Neovasculgen® in the List of Vital and Essential Drugs (VED) of Russia* which enables a significant increase in hospital purchases.

The Ministry of Health Commission made this decision on September 4, 2015 after thorough study of the drug’s safety, clinical efficacy and pharmacoeconomics. The corresponding government directive was signed on December 26, 2015 (№ 2724-p) - Neovasculgen® was included in the VED list under the group name “Plasmid Deoxyribonucleic acid [supercoiled circular double-stranded]”

In addition to the Russian market, HSCI intends to make Neovasculgen® available on other markets as well. In February 2013 marketing authorization for Neovasculgen® was received in Ukraine. In 2016 HSCI started the process of development and FDA clearance for the launch of the drug candidate based on IP linked to Neovasculgen® in the United States.

The innovative drug Neovasculgen® was developed by HSCI 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) - a serious, incapacitating disease which strikes 202 million people worldwide.

In Russia, there are 5 million diagnosed PAD patients (every year 300 thousand people are diagnosed with PAD). The number of patients with critical form of the disease (Critical Limb Ischemia) annually amounts up to 145,000, of which 35,000 - 40,000 undergo amputations, while around 25% of patients die. A part of patients diagnosed with CLI is inoperable, and for them Neovasculgen® could be the only treatment, allowing the opportunity to evade amputation as well as to significantly improve the quality of live.

Neovasculgen® is a drug whose action mechanism – therapeutic angiogenesis – introduces a new approach to treating ischemia: the use of an evolutionarily programmed process of blood vessel creation and growth.

Containing the gene of the Vascular Endothelial Growth Factor (VEGF) embedded in a plasmid vector (carrier), Neovasculgen® stimulates the growth of collateral blood vessels (аngiogenesis) and, as a result, promotes a long-term therapeutic effect and improves patients’ quality of life, first of all manifsted in a substantial increase of Pain Free Walking Distance.

According to the drug’s clinical trial data and results of its use in practical healthcare, Neovasculgen® increases the functioning capillaries number in ischemic tissues, improves the blood supply and reduces the rate of amputation in patients with lower limb ischemia, especially in those who are inoperable for an occlusive PAD. In addition, Neovasculgen® can be applied in combination with surgical revascularization to improve the long-term results of reconstructive operations.

Neovasculgen® has a long-term effect (3-5 years** – compared to 6-8 months for standard therapies) and can be effectively applied at PAD, including CLI (Stages 2a-3 of low limb ischemia according to Fontaine-Pokrovsky).

In addition, the drug has a significant healthcare economic efficiency (cost-saving effect).

As Neovasculgen® is the first-in-class gene therapy product for PAD treatment via stimulation of angiogenesis, the drug has much potential for use in treating other conditions where the development of collateral blood flow is beneficial. HSCI plans to implement new clinical trial protocols in order to expand the range of indications for applying Neovasculgen® (other nosologies beyond PAD/CLI). To start with, HSCI aims to work in the therapy of Diabetic Foot Syndrome, IHD (Ischemic Heart Disease) and treatment of trauma-induced peripheral nerve damage. In October 2016 HSCI received a permission to start clinical trials for Diabetic Foot Syndrome in Russia, while in September 2016 HSCI's subsidiary "NextGen" Co. Ltd. received a patent for gene-therapy method of Diabetic Foot Syndrome treatment.

In addition, the R&D is in progress for the creation of gene-activated bone grafts based on Neovasculgen® (e.g., see: HSCI’s Poster Paper Selected in TOP 25 at 2015 TERMIS World Congress; Ordinary and Activated Bone Grafts: Applied Classification and the Main Features. Biomed Res Int. 2015;2015:365050. doi: 10.1155/2015/365050 – https://www.hindawi.com/journals/bmri/2015/365050/).

The Company also aims to create new gene-therapy drugs based on different constructions and genes, maintaining its status as a leader in the development and promotion of gene therapy on the pharmaceutical market.

* The Vital and Essential Drugs (VED) List is a register of pharmaceutical drugs approved by the Russian Government in order to provide state control over prices to increase availability of essential medicines to the people of Russia. The VED List mainly serves as the basis for drug purchases by hospitals and for recommended treatments of various diseases.

**According to the published data, the therapeutic effect following a treatment course of Neovasculgen® continues for up to 5 years:  3 years – aggregated data (see: http://ishemii.net/stati/Pyatiletnie-rezultaty-lecheniya-bolnyh-hronicheskoj-ishemiej-nizhnih-konechnostej-s-ispolzovaniem-gennoj-terapii); 5 years – from 1 clinical site (see: http://ishemii.net/stati/Vozmozhnosti-gennoj-terapii-pri-hronicheskih-obliteriruyushih-zabolevaniyah-arterij-nizhnih-konechnostej), aggregated data will come soon.


  

See also:

 Marketing authorization in Russia - Registration certificate (perpetual)

Notorized translation of perpetual registration certificate to English

 

 Journal of Cardiovascular Pharmacology and Therapeutics, March 13, 2015 "pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia"  






American Journal of Cardiovascular Drugs,03 January 2017 "Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety and Efficacy in 210 Patients with Peripheral Arterial Disease"
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NATURE about Neovasculgen:
Nature Medicine (March 2012, V.18, № 3, p.328)

Website: www.neovasculgen.com

http://ishemii.net/