Innovations in Russian pharmaceutical production: the patient is probably alive...
Russia in the innovation marketIrina Shirokova, Remedium magazine No. 1-2008
Every year, 30-40 new original drugs appear in the world, created on the basis of the latest scientific discoveries. These drugs are created in the research centers of Western pharmaceutical corporations. What prevents domestic pharmaceutical manufacturers from closely launching innovative drugs, especially since in most cases the introduction of these drugs to the market opens up new opportunities for therapy and ensures financial success for the developer company?
There are new items, but the market does not see themIn recent years, the domestic pharmaceutical industry has been relatively stable and developing to some extent, but the main problem of the drug range remains the lack of innovative drugs.
Russian pharmaceutical manufacturers, as a rule, refer to the high cost of developing and promoting new drugs, the lack of confidence that their investments will pay off.
It is known that in Russia the budget for the development and implementation of innovative drugs ranges from $ 100,000 to $ 5 million, whereas in the West it is orders of magnitude higher: from $ 100 to $ 500 million (for generic companies – $ 2-20 million). And it is Western companies that are the main suppliers of innovative medicines. There are several reasons for this. Firstly, Western developers are supported to a certain extent by the state. "In Europe and the USA, there are special regulatory mechanisms designed to stimulate investment in the development of innovative drugs, such as, for example, the law on orphan drugs (exclusive marketing rights, tax benefits). In addition, in a number of cases, the state participates in financing the development of such drugs, – notes Igor Krylov, CEO of JSC "Pharmstandard". – In Russia, the creation of innovative drugs – and these are the most expensive drugs in the pharmaceutical market – is a risk zone exclusively for the developer." Another serious reason, according to Roman Ivanov, head of the medical department of OAO Nizhpharm, lies in the absence of structures in our country aimed at developing innovative medicines: "None of the Russian research institutes is currently able to solve the problem of developing a turnkey drug. Often only one of the stages is implemented, for example, preclinical development, i.e. search synthesis of a molecule. Further projects are frozen, because serious financing is required at the next stages."
The development that has not passed the entire cycle of clinical trials (CI), as a rule, is not interesting to Russian pharmaceutical manufacturers. Few dare to take the risk that is inevitable in this situation. Few people seek to conduct numerous CI and registration of drugs.
Andrey Belashov, Development Director of JSC "Domestic Medicines", explains this situation by the gap between science and production, which arose at a certain stage of the development of the domestic economy. He sees the key problem for Russia in the gap that has formed in recent decades between science, which lacks funding, and marketing: "It is not enough to create and produce a drug. It still needs to be skillfully brought to the consumer, to make information about it accessible, and to demonstrate to the target audience the unique properties and advantages of this product over existing competitors. Companies that have not only a well-developed marketing strategy, but also a huge resource in the form of employees working with doctors and pharmacists can afford it. And there are few of them. As a result, a crisis situation has formed in Russia, when scientists declare that there are products and they have been created, but the market does not see them."
But even if, contrary to everything, a domestic innovative drug has been created and found its place in Russia, the insufficient level of laboratory (GLP) and clinical (GCP) studies, as well as production standards (GMP) prevents its introduction to a wide world market. But this could significantly increase sales and return the investment faster. In the West, representatives of "big pharma", developing a new drug, consider the whole world as a market. As a result, the payback period of their products and the volume of return on investment are completely incomparable with the sales volumes of domestic pharmaceutical manufacturers: in Russia, a product with sales of more than $ 5 million is considered successful, whereas in the West, registration of only one drug by one indicator costs about 5 million euros.
At the same time, we should not forget that a domestic pharmaceutical company should be ready not only for significant development costs without 100% guarantees of success, but also for the upcoming competition with global giants to promote new products to the market. In such a situation, the creation of innovative medicines in Russia turns into a lottery. It is not surprising that domestic pharmaceutical companies choose a well-predicted course for the reproduction of medicines that have lost patent protection.
What is in the portfolio of the Russian developer of the drugHow innovative are domestic drugs?
There is no definite answer to this question, because opinions differ very much about which drugs can be considered innovative. According to Roman Ivanov, "at the moment, innovative drugs as such are not produced in Russia. Successful foreign projects for the development and production of innovative drugs, first of all, are distinguished by a high level of evidence base, as well as acceptance by the market." And yet innovative drugs are gradually appearing in the portfolio of Russian companies. They differ from world developments in their scope and sources of origin.
In the West, most of the innovations and aspirations of scientists are aimed at combating socially significant diseases, such as diabetes mellitus, bronchial asthma, multiple sclerosis, oncology, tuberculosis, arterial hypertension. More and more research is being conducted in the field of bio- and genetic engineering technologies. At the same time, the main source of innovation for Western corporations is their own developments, or developments purchased from other companies.
In Russia, traditionally, great attention is paid to drugs for the normalization of the central nervous system and antiviral drugs. Domestic pharmaceutical manufacturers are introducing new immunomodulators and anticancer drugs, psychostimulants, painkillers and antidotes to the market. These drugs are characterized by high efficiency, safety and mass demand on the market, but they were created in Soviet times. They are either the results of the work of the Research Institute, or born in the depths of the military-industrial complex and the space industry.
The ideas of Russian scientists are being implemented by mini-companiesThe trend of the last decade can be attributed to the appearance on the Russian market of so-called "mini-companies" specializing in the production of innovative drugs and having 1-4 products in their assortment.
Such companies include Feron (the drug Viferon), Geropharm (Cortexin, Retinalamine, Rinsulin), Petrovax (Polyoxidonium, Grippol, Longidase), Medicor (Galavit), Ecopharminvest (Mexicor), Miraxfarma (Indinol, Epigallate), etc.
As a rule, the source of innovation for mini-companies is the development of domestic scientists. For example, Feron LLC produces the immunomodulatory and antiviral drug Viferon, created on the basis of the N. Gamalei Research Institute of Epidemiology and Microbiology of the Russian Academy of Medical Sciences. The Petrovax company produces original drugs created on the basis of fundamental scientific research of the SSC Institute of Immunology. The products of the mini-company are produced at their own or leased facilities and use, within the available capabilities, the methods of promotion typical of medium and large pharmaceutical manufacturers.
Work on bugsThe existing conditions in the country can hardly be called favorable for conducting domestic research in the field of creating innovative medicines.
Pharmaceutical companies and research centers cannot afford large and high-risk investments in the development of innovative medicines. In addition, a typical situation for our country is when domestic developments that have won the trust of doctors and patients, successful in pharmacy retail, are unclaimed in state market segments (DLO).
Russia, as well as all major developed countries, is characterized by the prevalence of cardiovascular and metabolic diseases, rapid aging of the population. In this regard, the costs of healthcare, including the provision of medicines to citizens, will constantly increase. In these conditions, Igor Krylov believes, the state should take the necessary measures to develop the domestic scientific base and stimulate the pharmaceutical industry: "It is the state that has the regulatory mechanisms that can allow the full use of Russia's scientific potential and strengthen its technological capabilities. The implementation of the state strategy for financing Russian science and the creation of a number of conditions for domestic manufacturers, including the purchase of domestic drugs under state programs, will not only solve internal problems, but also increase the export of high-tech goods from Russia. I want to believe that among such giants as the mining industry and the military-industrial complex, the potential of the pharmaceutical industry will also be noticed." According to Roman Ivanov, consolidation of efforts of Russian scientists and pharmaceutical companies can contribute to the way out of this situation. The common aspiration should be to identify and realize the scientific potential of domestic pharmacological science for the production of new effective drugs.
For example, the company "Nizhpharm", seeking to attract new drugs to its portfolio, in 2006 launched the "New Medicine" program, the purpose of which is to assist scientists seeking to develop and master the production of new drugs based on the results of their scientific research. "The implementation of the New Medicine program will make it possible to take an important step in the development of the scientific potential of the domestic pharmacological science," Roman Ivanov is sure. – The successful results of the project will satisfy the interests and needs of all parties: researchers – in the possibility of financing and joint implementation of their developments with the pharmaceutical manufacturer, the state – in providing support for the development of the scientific potential of domestic pharmacology, Nizhpharm – in replenishing the product portfolio with new drugs, and, most importantly, consumers who will have the opportunity to purchase modern effective drugs at affordable prices. The first months of the program's implementation showed that Russian science still has significant intellectual potential. We hope that our cooperation with scientific academic institutions will become even more productive in the near future."
"In general, the lack of innovative molecules is characteristic of the whole world," says Andrey Belashov. – Leading minds in all countries are engaged in their search. However, each new discovery, especially a brilliant one, is the result of many years of efforts by thousands of teams and, therefore, requires huge investments. Therefore, one of the tasks facing Western developers is to reduce costs. That is why the largest pharmaceutical companies – American, European, Japanese – are moving their research centers to China and Russia. In the West, the creation of innovative molecules is a systemic process, to a lesser extent related to the human factor and the genius abilities of a particular researcher. In Russia, on the contrary, there is no clear system in the presence of brilliant minds.
The emergence of their own innovative drugs on the Russian pharmaceutical market is hindered, on the one hand, by insufficient material and technical equipment of leading research institutes, and on the other hand, by a large outflow of the country's intellectual potential over the past years. Fortunately, this situation is changing, young people are no longer leaving for the West. Financing of Russian research institutes and their developments by either the state or pharmaceutical companies, as well as the presence of a strong personnel reserve, can improve the situation."
Henrik Konarkowski, Leading Business Development Consultant at Torrey Pines Investment (USA) (from the report "Development of own new drugs as a way to increase the IPO result. International Practice and Opportunities for Russia", February 27-28, 2007, II All-Russian Conference "Pharmaceutical Business in Russia: Reforms and the Market"):
– There are several options for developing new drugs for Russia today:
1. Development of new drugs using high-performance screening. This is 6-7 years and up to $ 50 million per 1 HP.
2. Development of a patented drug that "replaces" the Western brand in the Russian Federation. This is 3-5 years and up to $ 15 million per 1 HP.
3. Bioisosteric modification of old medicines to create a patent brand in the Russian Federation. This is 2-3 years and up to $ 5 million per 1 HP.
4. Modification of the "delivery" of old drugs into the body using nanobiotechnology. This is 2-3 years and up to $ 5 million per 1 HP.
Igor Krylov, CEO of JSC "Pharmstandard":
– Pharmstandard is not engaged in the development of new drugs, but we see our role in organizing the production of domestic developments and bringing them to the end consumer. Our company cooperates with a number of the largest Russian scientific centers: the State Research Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences (the result of cooperation is a hepatoprotector with antiviral action "Phosphogliv"), the Institute of Bioorganic Chemistry named after M.M.Shemyakin and Yu.A.Ovchinnikov (growth hormone "Rastan"). These drugs belong to the category of innovative drugs. So, for example, in the production of "Phosphogliva" a new original technology is used, providing nanoscale phospholipid particles, which significantly increases the bioavailability and effectiveness of the drug. Another innovative development in the company's portfolio is the drug Arbidol, which has an antiviral and immunostimulating effect. Arbidol affects not only widespread influenza subviruses, but also a number of other viruses. Now we are actively developing the genetic engineering direction. After the launch of insulins and growth hormone, we plan to release a drug for the treatment of oncological diseases – Filgrastim to the pharmaceutical market.
Andrey Belashov, Development Director of JSC "Domestic Medicines":
– Our company works both in the field of creating original molecules and in the field of creating therapeutic analog molecules (mee-too). We are trying to find new properties with an improved side effect profile, a pharmacokinetic profile and increased efficiency. The source of replenishment of original drugs for the holding "Domestic Medicines" is, on the one hand, planned and thoughtful cooperation with leading research institutes and medical universities, on the other – the development of ideas by employees of the holding and their further development together with the same institutes, primarily with the institute "Himrar". Back in 2003, "Domestic Medicines" declared itself as the first Russian company that is going to actively introduce original developments of domestic scientists in the Russian pharmaceutical market. Since that time, the creation of original innovative medicines or products with signs of originality remains a priority in the strategic development of the company. In recent years, we have introduced several original drugs to the Russian market, including Phenotropil and Zorex. These products were at the level of an idea or were at the stage of preclinical research, but we brought them to the market: we conducted CI, registered, and determined a marketing strategy. But first of all, "Domestic Medicines" created a structure that allows evaluating the offers that are available on the innovation market, prospects and risks associated with the release of new products to the market. We have regulated procedures for the research of these drugs, the development of marketing strategies and the introduction of these products to the market. There are 4 departments of the company working in this direction. Analysts study the market from the point of view of quantitative perspectives. Doctors evaluate the therapeutic benefits of new drugs. Marketers analyze how to translate these advantages into money. A group of product managers cooperates with the medical department and the Department of Advanced Development and Innovation.
Roman Ivanov, Head of the Medical Department of JSC "Nizhpharm":
– Nizhpharm specializes in the production of branded generic drugs ("line extension"). At the same time, the company's competitive advantage is the production of so-called generics plus (or generics with signs of originality), i.e. drugs with additional therapeutic properties. For example, our drug Fungoterbin, being a generic with the main active ingredient terbinafine, has a noticeable difference – it contains urea, which determines additional medicinal properties. Another example is the drug Vitaprost. Once it was used only in the form of injections, but Nizhpharm began to produce it in the form of suppositories, as well as suppositories with a doubled dosage – Forte, as well as in tablet form. Nizhpharm traditionally concentrates its efforts on the creation of drugs used in dermatology, gynecology, urology, as well as drugs for the treatment of musculoskeletal diseases and gastrointestinal diseases. Therefore, the development of innovative drugs is expected primarily in these areas. The possibilities of developing new products of other pharmacotherapeutic categories are also analyzed. The source of our innovations are the developments of leading scientists and research centers of the Russian Federation, with whom we cooperate within the framework of the New Medicine project, as well as the relevant divisions of the company.
Olga Chernova, Deputy. General Director for Development of the company "EcoFarmInvest":
– Since 2000, the pharmaceutical company Ecopharminvest LLC has been developing a promising direction in the treatment of cardiovascular diseases - metabolic cytoprotective therapy. This work is carried out in cooperation with leading scientific institutions of Russia – the All-Russian Scientific Center for the Safety of Biologically Active Substances, the N.N. Semenov Institute of Chemical Physics of the Russian Academy of Sciences, Kursk State Medical University. The result of our joint activity was the drug Mexicor, which can be attributed to the drugs of the additional (extended) line ("line extension"), having new approved applications (indications) or being an improved / alternative formulation of an existing drug. Currently, Mexicor is produced under the license of LLC "Ecopharminvest" SUE "State Plant of Medicines" (in the form of a solution for injection) and FSUE "Moschimpharmparaty" named after N.A.Semashko (capsules) based on a medicinal substance produced by a subsidiary of LLC "Ecopharminvest" – LLC "BION" (Obninsk), commissioned 2 years ago and fully compliant with GMP conditions. Mexicor is an Rx drug, therefore, when promoting it, the greatest importance is attached to institutional advertising. It is educational in nature and serves as a valuable source of information for professionals when choosing treatment methods. At the same time, we pay great attention to the reputation of the publication: often a positive attitude of doctors to advertising arises simply against the background of trust in the publication in which the advertising article is placed.
Elena Pokshubina, General Director of Miraxfarma:
– MiraxpHarma and MiraxbIopHarma are the first domestic pharmaceutical companies that have started developing and implementing targeted drugs that target molecular targets mediating the pathogenesis of hyperplastic and neoplastic diseases of the reproductive system. The first two such drugs – Indinol (active ingredient – indole-3-carbinol) and Epigallate (epigallocatechin-3-gallate) – have already entered the pharmaceutical market as means of pharmacological correction of gynecological diseases such as fibroids, endometriosis, mastopathy. So far, these drugs are registered as dietary supplements. But now there is a process of registering these and other products as medicines. In November 2007, two new products will appear on the Russian market – Indigal and Promisan. The first of them blocks the pathological growth of cells in the prostate tissue, the main field of application of the second drug is oncology. All these drugs are innovative. They were created and tested at the Research Institute of Molecular Medicine of the I.M.Sechenov MMA. Although the substances themselves are well known in the West, drugs based on them are not produced there due to problems associated with the instability of molecules, their pharmacokinetics and pharmacodynamics. Several dietary supplements produced abroad containing these components are not characterized in terms of purity, stability and biological action. Russian scientists, on the basis of imported substances purchased, were able to create drugs that are stable, high purity and active. Our products are manufactured at the own facilities of the research and production company CJSC Mirax-Biopharma on the leased premises of the Institute of Chemical Rarities (a branch of the American Institute ChemDiv) in Khimki. The production is organized in full compliance with the requirements of the national standard (GMP). Since 2004, we have been constantly participating in thematic conferences, conducting educational seminars for doctors, writing and publishing monographs and manuals, posting information on the company's website. Recently, a "hotline" was organized. And of course, medical representatives working all over Russia play a big role in promoting our drugs.
Lina Yudina, Deputy General Director for the Development of CJSC "CSM "Medicor":
– The Russian company CJSC "CSM "Medicor" produces an innovative immunomodulatory and anti-inflammatory drug Galavit. The drug has no analogues in the pharmaceutical market. Galavit belongs to synthetic, chemically pure drugs, is an aminodihydrophthalazinedione of sodium and has been approved for use since 1997. A 10-year experience of clinical use of the drug Galavit in Russia, and in recent years in Ukraine, allows us to recommend it as the drug of choice for the treatment of a number of infectious diseases, as well as inflammatory processes leading to local reduced immunity. The company CJSC "CSM "Medicor" has a number of patents, including a patent for an immunomodulatory drug and a trademark of the drug. Galavit is produced at the pharmaceutical plant of the company "Medicor" in Belgorod. The production complies with GMP standards, which is confirmed by the corresponding license of Roszdravnadzor. Galavit has two dosage forms of release: powder for the preparation of a solution for injection and candles. The injectable form is promoted according to all the laws of prescription drugs: we work with doctors, conduct CI, inform the medical community about the results obtained at symposiums and conferences. In addition, the company promotes the drug by participating in specialized exhibitions. With the over-the-counter form, we reach out to the patient: we give information in the most rated publications, the most widely read and the most "intellectual" journals. Not so long ago, the company began developing a drug in the form of sublingual tablets for use in dentistry and otolaryngology. In addition, we have expanded the scope of the drug to include pediatrics (registration is at the completion stage). To date, Galavit is used in the treatment of 13 nosologies.
Portal "Eternal youth" www.vechnayamolodost.ru23.10.2008