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Epygen Biotech to produce recombinant Streptokinase (rSK) for the cardiovascular segment

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Debayan Ghosh – President and Founder, Epygen Biotech shares insights on the current opportunities and  challenges in the biosimilar industry and speaks about Epygen Biotech’s offerings for the industry

How do you see the growth of biosimilar market in India? What are the growth drivers?

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Debayan Ghosh

Taking the past few years in to consideration, the Indian market has doubled in size in the biosimilar space. The biosimilar market has grown by 30 per cent due to rise in domestic business, exports, mergers and acquisitions and new product innovations. Over the past five years, this industry has steadily grown by a 30 to 50 per cent and this sector at present employs more than 30,000 biotech scientists, who continue to drive growth. The current scenario is that the Indian market accounts over 1.1 per cent of the global biotech market. However, its rapidly growing capability is likely to position India as a leading player in the years to come, posing a triple digit growth in the next decade. India ranks third in the Asia-Pacific region, after Japan and Korea and among the top 12 globally. There is constant monitoring done by the Central Drugs Standard Control Organization (CDSCO) and the Department of Biotechnology to improve the 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 biosimilar market size to the vicinity of $50 billion by 2030!

As India’s biosimilar market is expected to increase from $186 million in 2016 to $1.1 billion in 2020. How are you planning to utilise the opportunity?

There is no doubt that the Indian market for biosimilars is getting competitive and busy and will continue to be so. While the number of Indian companies to make it to the developed markets are still few, the Indian market itself will continue to see multiple players diving in, including international companies marketing products through collaborations. It indeed is a big task to accommodate the paradigm shift resulting from upsurge of biosimilars, a business which had been traditionally dictated by multinational inventor corporations.

Indian life science firms are investing in biosimilars development to tap this growing opportunity and several of them are opting for acquisitions and alliances to get biologics skills and the latest manufacturing technologies to be able to succeed in a complex regulatory environment. Development of biosimilars is dependent on significant investments, not only in terms of time required to bring a single drug to market but also the cost associated with its research. A company may require around $20 million to set up an R&D centre in India, excluding substantial expenses such as clinical trials. These opportunities offered by biosimilars would be faced by steep regulatory hurdles of adopting framework, along with the cost associated with conducting clinical trials in various geographies. There is no doubt that setting up and running a manufacturing plant for biosimilars will be definitely much more difficult and costlier than that for small molecules. Epygen is utlising its resources and vast experience of expressing quality recombinant proteins in large quantities and at an affordable cost, within the most stringent regulatory framework, to steer its ways into the world of biosimilar possibilities.

What are the challenges faced by the biosimilar industry and how are you planning to overcome it?

Taking the current market scenario, biopharma is emerging as one of the hottest segments of the pharma industry and is expected to reach $390 billion by 2020 where biosimilars will account for at least 10 per cent of the overall biologics market, if not much more! Currently, the biosimilar industry in India has just entered into a nascent stage, opening up the gates for the country to make a statement in the world biosimilars scene in times to come. Biosimilar manufacturing is far more complex than generics, as the drugs are often derived from recombinant living cells and protein characterisation and purification still remains immensely elusive. The manufacturer of biosimilars in various stages of development is staggering and the stakeholders focus on driving its value by delivering quality healthcare, effectively managing cost and patient outreach. Developing and manufacturing biosimilars is particularly challenging in terms of quality, safety, and efficacy, closely matching an already licensed reference product, being difficult to standardise such inherently complex products based on complicated manufacturing processes.

Brief us on the R&D in biosimilar space in India.

R&D expenditure for biosimilar development in India increased substantially to $1.4 billion during the year ended March, 2015, a 28.8 per cent increase from $1 billion in the previous year. [Source: OPPI November 2015 – Assocham]. This increased R&D expenditure is a result from the engagement of lifescience companies from large biopharma, major generic companies, young biotech JV ventures and start-ups developing skills for biosimilars manufacturing. It is reported that there are more than 10 companies in India, genuinely developing biosimilars for the highest selling monoclonal antibodies of the world. Even globally, the technology development landscape for biosimilars reflects deeper engagement. The current vibrant landscape includes companies across the spectrum of large, mid-sized and smaller ventures. With several active global programmes on biosimilar opportunities, there is a good possibility today to partner for technology access. While technology still remains key to competitive biosimilar business, its threat as a barrier is diminishing given the expanded global partnership possibilities.

Tell us about the major R&D focus areas of Epygen Biotech.

Oncology: Epygen’s Bevacizumab is a recombinant humanised monoclonal IgG1 antibody that will bind to and inhibit the biologic activity of human vascular endothelial growth factor (VEGF).

This monoclonal antibody targeting VEGF was the first FDA approved therapy designed to inhibit tumour angiogenesis. Therapeutic use of this antibody aims at metastatic colorectal cancer, non-small cell lung cancer, recurrent glioblastoma, metastatic renal-cell carcinoma, recurrent platinum-treated cervical cancer, advanced ovarian cancer and age related macular degeneration (AMD).

Oesteoporosis: Teriparatide Teriparatide is aimed for the activation of osteoblasts more than osteoclasts leading to an overall increase in bone growth of the patients having osteoporosis. Usually, Osteoporosis is treated with anti – resorptive agents (bisphosphonates, oestrogens, selective estrogen receptor modulators etc.), but teriparatide has a unique mechanism of action. While endogenous PTH is responsible for bone demineralisation, exogenous PTH stimulates osteoblastic activity. This drugs is aimed for use in postmenopausal women with osteoporosis.

How do you ensure quality, affordability and accessibility of your product?

Due to certain reasons, biological drugs remain inaccessible to most patients in the emerging markets as the biosimilars represent a compelling proposition for patient affordability and access. However, quality concerns, technology hurdles, lack of robust regulatory frameworks, and development timelines and costs are key hurdles for biosimilars in these markets. Epygen has a fantastic team of scientists who scrutinise quality from start to end. One of the important factor that we looking at, is our product affordability for the patients and easy access to all regions in the country. Epygen has its aim clear and we as a team have been working towards it. Epygen Bioprocess Engineers take care of the various aspects of process optimisation, HCD Fermentation and scaling up of the technologies to maximise the expression levels of the protein of interest to the highest levels. The downstream scientists and engineers precariously design the steps like cell lysys and solubulisation and finally the chromatography experts make sure that the purity of the protein is achieved to 100 per cent, devoid of any junk proteins or endotoxins whatsoever. Epygen’s internal regulatory team makes sure that global standards are adhered to and all the quality checks and paper works are in place.

Epygen Biotech (EBPL) would be launching its entry biosimilar molecule Recombinant Streptokinase (rSK) in 2018. Tell us more on this.

Currently, my team and I are only focusing to produce the recombinant Streptokinase (rSK) for the cardiovascular segment under License and Technology support from CSIR Govt of India. We want to make this life-saving cardiovascular thrombolytic drug for the people of this country as the statistics say 17 lakh people die of heart attacks in India every year. It is the need of the hour to produce rSK for patients in the Indian subcontinent and the underprivileged of the world, at an affordable cost, while maintaining highest quality and abiding stringent international regulatory standards.

A biosimilar rSK product results in a further reduction in infusion associated side effects by eliminating materials with pyrogenic and/ or hypotensive effects from preparations. The new version of rSK non-Beta lactum clone further increases safety profile for this protein as a life saving drug.

Are there any other products that are there in the pipeline for 2018?

There are quite a few exciting products in the 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.

What is the roadmap of the company for next five years?

Epygen Biopharmaceutical pipeline consists of E.coli based products like GCSF, PEG-GCSF and Teriparatide, and also CHO cell based products like Bevacizumab. In the first unit at Patalganga, Epygen has planned to produce the E.coli based products and fill them in vials, pre-filled syringes and cartridges depending on specific demand and business plan. The animal cell culture facility has been planned to follow suit in the adjoining area belonging to Epygen. Expression levels, purification and dosage preparations have been carefully panned to cater to India, South Asia region and the semi-regulated global markets coming under the regulatory framework of WHO. While the worldwide sales of Bevacisumab and Pegfilgrastim contributes $7.2 billion and $4.8 billion respectively, these molecule’s sales in India are less than Rs 100 crores each, owing to the price barrier presented by the innovators. 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 meagre numbers, rendering these drugs more affordable for patients in the region. The rSK has been planned for launch by 2019 and by that time at least one other E.coli based biosimilar has been planned to enter pre-clinical trials, and subsequently the other molecules will follow.

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