"India's rapidly growing capability is likely to position it as a leading player in Biosimilars"

Debayan Ghosh
President & Founder,Epygen Biotech
Debayan Ghosh Co-founded and built Epygen in the year 2006 with a vision to emerge as a leading biotech innovator enhancing human life. Epygen's current focus area is to produce and launch Biosimilar Recombinant Streptokinase (rSK) for the cardiovascular segment under License and Technology support from CSIR Govt of India. In an interview with Mahesh Kallayil, Mr Ghosh talks about biosimilar market in India, their process of completing the Regulatory Pathway of cardiovascular Thrombolytic Recombinant Protein drug for patients in Indian subcontinent and the underprivileged of the world and his aim to produce this Life-Saving drug to address the mid income strata and bottom of the pyramid.

Can you tell us about company's journey till date?

Epygen group was conceived nearly a decade back outside India, in Dubai Science Park and Colorado USA, by two persons of Indian origin, me and my long time friend Ariyarathenam. Our connecting thread was Biocon. While I was one of the first Biotech graduates in India who went on work for Biocon as a campus recruit, Ariyarathenam was running an agency for Biocon in south Asian countries for several years. After 5 years in Biocon and 7 years working for a US Biotechnology company based in south Florida, I started Epygen in 2006. Ariyarathenam soon joined in, and a few years later, his son Ineeyan, a business graduate from the King's college of London, joined the team. We started Epygen in India with the funds that we earned from our Biotech ventures abroad, as a 100% FDI setup. With our several years of experience of Fermentation, Protein expression and purification, we decided to focus completely on Biopharmaceuticals development and manufacturing in India and chose recombinant Streptokinase, a cardiovascular thrombolytic protein, as our entry product to Biosimilars. We quickly tied up with CSIR -IMTECH in Chandigarh India to license in its Recombinant Streptokinase technology, from lab scale technology transfer to scaling up and expression of proteins up to pre clinical and clinical scales. Under the able guidance of the then director of CSIRIMTECH, who was also and the leader of Streptokinase research in the world, we went on cracking the puzzles of a newer version of streptokinase. Our aim was to make it safer for patients, produced it more efficiently and also utilize our skills in process optimization and protein engineering to enhance the expression levels, making this critical life saving protein more affordable to the masses in India and the region. Department of Biotechnology agency BIRAC acknowledged our efforts to improve this technology for the unmet needs in India, where 15 Lakh people dye of heart attack every year. They extended financial assistance for our research, injecting a big boost to our enthusiasm and purpose. We went on to construct a state of art Recombinant Biotech and Protein Purification lab in Navi Mumbai, employing top Biotech scientists experienced in USA and India, whose the focus was to imbibe the technology that was being transferred and continue further development and fine tune. Subsequently, we started the work to construct a 60,000 square feet Biopharmaceutical facility in Patalganga, Maharashtra, to expand our research activity by several folds and further produce these Biosimilar proteins in commercial scales. Epygen's recombinant proteins are in regulatory stages of Pre-clinical Trials with the recombinant Streptokinase to be launched by 2019 and an exciting pipeline of other e-coli based technologies e.g PEG GCSF (a Chemo Induced Neutropenia protein drug) and Monoclonal Antibodies for Oncology, making steady progress.

How is the company positioned in the Indian and global market ?

Let me talk about our stepping stone protein Recombinant Streptokinase. Epygen is amongst very few companies in the world to produce Recombinant Streptokinase, the only affordable thrombolytic injection for STEMI(ST Elevated Myocardial infarction patients). Amongst Cardiovascular disease patients and number of people suffering strokes in urban and rural part of India, at least 0.5% of Indian population is at risk of suffering from myocardial infarction Cardiac stroke. This gives a potential of 6.0 million cases of thrombolytic treatment in India. Though for urban patients with higher economic capabilities, the top preferences would be tPA, 60% of urban population and nearly 100% of the rural population would be potential candidates for streptokinase treatment in our country. From the market figure on number of vials sold per year by the major brands, the current usage covers a miniscule portion of the potential. This indicates a huge influx of undocumented and spurious/unreliable thrombolytics being used in the country. Streptokinase is by far the most economic Thrombolytic agent available, costing approximately Rs.2,000-3,500 for a full dose of 1.5 million units. Mainly because of its cost, it remains the most used agent in clinical practice in the country. In addition, the recombinant version is free from streptolysin/streptodornase associated with natural Streptokinasem making it safer for use. tPA based innovator drugs on the other hand, are the most expensive agents available for this treatment segment, costing approximately Rs 40,000 per full dose. Another available tPA Biosimilar agent in India costs approximately Rs 25,000 per dose. This comparison shows that for a cost sensitive Indian market, affordability still remains a limiting factor for most of these Thrombolytic agents except for Streptokinase. Streptokinase is widely used as a first line of treatment for STEMI patients across the globe, especially in Asia, African and Latin American countries, each of which market Epygen is going to target. Our pipeline products like GCSF, PEG GCSF, Recombinant Hormones and Monoclonal Antibodies project billions of dollars biosimilar market in the regulated and semi-regulated markets.

How does the company keep abreast with the ever-changing trends in biopharmaceutical market?

Epygen engages continuously in conducting market intelligence exercise employing agencies like IMS etc., in addition to its Biotech network worldwide, which provides access to all the exciting scientific and commercial developments in the field of Biopharmaceuticals. We participate in global conferences, where we often contribute scholastically and our scientists are encouraged to continuously update their outlook through such events.

How do you see the biopharma market in India maturing ?

The Indian biotech market seems to have doubled in size in the past few years! This is expected, since it was very negligible to start with. The industry grew by a whooping 30%, fueled by the rise in domestic business, exports, mergers and acquisitions and new product innovations. Over the past five years, the industry has reportedly grown steadily by a 30 % to 50 %. The sector at present, employs more than 30,000 Biotech scientists, who continue to drive growth. Even then, the Indian market currently accounts for a little over 1.1 % of the global biotech market. However, its rapidly growing capability is likely to position it as a leading player in the years to come, especially in the area of Biosimilars, posing a triple digit growth in the next decade. India already ranks third in Asia-Pacific, after Japan and Korea and among the top 12 globally. The Central Drugs Standard Control Organization and the Department of Biotechnology constantly monitors and improves biosimilar drugs policy and regulatory pathway, for manufacturing processes that aims to deliver safety, efficacy and quality of international standards. This policy is expected to catapult the Indian biosimilars market size to the vicinity of US$50 billion by 2030!

How do you place India among the Asia-Pacific countries? Do you feel that India could be an important player in biopharmaceuticals?

At first glance, Asia undoubtedly appears to be an assured avenue of growth for pharmaceutical manufacturers on the whole. According to IMS Market Prognosis 2012, the pharmaceutical market in Asia is expected to reach USD 350 billion in 2016-17, comprising 30% of the global pharmaceutical market of USD 1.2 trillion and driving close to 50% of global, incremental growth. Taking a closer look at the top pharmaceuticals locatedin Asia-Pacific reconfirms the importance of China, Japan, and India whose companies make up 32.0 %, 42.0 %, and 14.0 % in terms of market capitalization by regional companies respectively. In addition, India pharma is expected to grow over 15 % per annum between 2015 and 2020, and outperform the global pharma industry benchmark. The market is expected to grow to USD 55 billion by 2020 , thereby emerging as the sixth largest pharmaceutical market globally by absolute size, as stated by Mr Arun Singh, Indian Ambassador to the US.

With a clear perspective that 75% of pipeline drugs globally are from Biopharmaceutical nature, and 8 out of 10 largest selling drugs in 2017 being from Biopharmaceutical basket, a total of 667 innovative biopharmaceuticals were launched in the U.S. over the past 20 years, bringing new treatment options to critical ailments. From a numerical perspective and anticipating the progress of drug candidates currently in the research and development pipeline, the state of biopharmaceutical innovation is robust. The source of the biopharmaceutical innovation that is successfully launched in the U.S. is highly diverse, with over 300 entities filing original patents to protect the intellectual property that became the basis for the 667 medicines that were launched.

Biologic agents will continue to outpace overall pharma spending growth and are expected to represent 19-20% of the total market value by 2017. The Asia Pacific biopharma market has exploded since the 1990s, with thousands of homegrown biopharma companies and major multinationals setting up shop across the region.

Can you explain more about Epygen's Biotech incubation facility at Navi Mumbai?

Epygen's incubation facility in Navi Mumbai is equipped with the state of art equipment for Recombinant Technology work, Fermentation, Protein Expression and Purification with a full fledged DSP line up. It can develop and express recombinant proteins based on a wide range of expression hosts and scale up process based on an array of molecular biology, protein engineering and bioprocess optimization techniques. It houses a strong team of scientists with experience in the United States and India specializing in the area of Bioprocess, Regulatory and Quality Assurance, apart from the core team of Molecular Biologists. It is equipped to express proteins of interest at various levels, model, monitor and scale up manufacturing of these critical therapeutic proteins based on the needs of Indian patients .

Could you please elucidate more on Epygen's Pegfilgrastim and Bevacizumab?

As stated earlier, 8 out of top 10 highest selling drugs in the world come from biotech origin, contributing sales of nearly $65 billion. While the worldwide sales of Bevacizumab and Pegfilgrastim contributes 7.2 Billion and 4.8 Billion USD respectively, sales of Bevacizumab and Pegfilgrastim from India are only INR 98 Cr and INR 84 Cr respectively, owing to the price barrier presented by the innovator. Harnessing the tools of Proteomics and improved bioprocess, which Epygen had been consistently able to do for several years, we are aiming to bring about a sea change in these meager numbers, rendering these drugs more affordable for patients in the region. With the highest quality standards that Epygen practices for therapeutic proteins, we are aiming to cater to the semi regulated markets world wide with these Biosimilar drugs and bring about some parity with the global numbers.

What do you see as the big drivers of innovation occurring in Cardiovascular therapy and oncology drugs right now?

There has been an increase in the prevalence of cancer and heart disease as the population ages.Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Modern treatment strategies have led to improvement in the chances of surviving a diagnosis of cancer; however, these treatments are expensive. Heart disease is the numberone cause of death in the US and in most high-income countries, followed by cancer, and for years deaths from both diseases have been on the decline.. A quick survey at new drug approvals over 2010 and the first half of 2011 shows that the cardiovascular sphere got just three new medications: Dabigatran etexilate(Pradaxa, Boehringer Ingelheim), Azilsartan medoxomil (Edarbi, Takeda Pharmaceutical), and ticagrelor (Brilinta, AstraZeneca). By contrast, 13 new drugs have been approved since January 2010 for different cancers. Drugs still in development paint an even starker picture: while cancer has over 700 drugs in development, the number of cardiovascular drugs in the pipeline is just 147.

As a biosimilar manufacturer, how you think the industry should balance between protecting the rights of a patent holder and providing affordable health care for all?

The issue of intellectual property and in particular patents is a matter of debate. The issue holds more significance with respect to pharmaceutical patents and the concerned stakeholders which has resulted in a fierce policy debate regarding patenting across the globe and especially in developing countries. It is widely believed that patients in developing countries are disadvantaged as newer medicines under patent are out of reach of millions either due to lack of access or due to exorbitant costs. The recent issue of compulsory license in India for Bayer's anti-cancer drug Nexavar (SorefenibTosylate), unveiled a host of issues. Since, multinational pharmaceutical companies may fear to introduce newer medical therapies in Indian market, it is important to repose their faith in the system so that new medicines are launched in India. Various measures such as monitoring of prices of patented medicines, negotiating the price of a patented medicine by the government before marketing, providing petty patents (utility patents ) for minor innovations, procurement of patented medicines by government for public distribution, encouraging healthcare insurance, fostering Industry -Institute partnerships etc. may help balance access to affordable medicines and incentive for innovators.

Can we have your take on patent cliff and its implications in generic market?

To avoid falling off the cliff, innovators often augment their patents by process patenting or somehow extend market exclusivity for their products utilizing some IP extension tools. for a One frequently used strategy is to procureadditional patents beyond the original patents that protect the drug's primary active ingredient and disease targets. A key question is to what level these later-issued patents protect valid features or methods, instead of serving as a business strategy to delay generic competition, simply as a barrier to progress. In some cases, the patent claim may be frail or largely duplicative of an already patented feature or product. These patents can amplify the cost for a manufacturer to bring a generic version of a drug to market and in effect delay approval of the generic drug after the patents on the underlying base compound expire.

It is well established that extending market exclusivity by extending or augmenting patents can have severe public health implications in our part of the world.

Please brief us on generic drug patent and FDA issues?

The average time for FDA approval has increased to nearly 8 years in recent times. There is a huge risk of economic burden due to such lengthy regulatory time for Biopharma companies. If the drug shows unpromising or average results in its clinical trial, then this leads to low or unpredictable sales and companies have no way to recover the cost invested on that molecule. In addition, intellectual property has made the market penetration even more difficult for Biosimilar drugs. In the case of drugs where the patent has been extended for an additional five years, it has been impossible for Biosimilar drugs to get in at a lower price point. The anatomy of an exorbitant cost of drug development is primarily related to government policies, FDA long-approval and time-consuming complex trials, that the Biopharma faces.