The Indian pharmaceutical industry has been aggressive in the R&D front especially during the last couple of years, apart from creating strong manufacturing and investing huge funds in upgradation and expansion. The industry has identified R&D as pivotal to upkeep its brand image.
The result-oriented R&D base enables to remain at the fore-front of emerging technologies and techniques, at the same time helping it to mitigate risks from technology obsolescence. Realizing India's potential as a manufacturing and research hub, several MNCs have already setup their R&D activities as well as manufacturing plants.
With the help of excellent talent pool, cost effective manufacturing base and easy availability of cheap raw materials, the Indian pharma industry is set to tap new opportunities in the field of contract manufacturing, contract research, clinical trials and biotechnology. The major international companies started looking at Indian companies as there prefer partners. The huge size of domestic market, implementation of Patent regime cost effective business operations and highest number of US FDA approved cGMP facilities assisting Indian pharma to fight competition in a friendly manner.
The changing lifestyles have altered the health needs of Indian, offering a plethora of opportunities to the pharmaceutical industry. Cardiovascular and anti-diabetics are two of the fastest growing segments in the Indian pharma market.
To overcome the problems of new patent regime, the Indian pharma sector geared its resources towards R&D. Though the R&D investment figures for 2005-06 for several companies have not yet available, the same for 25 major companies during the year 2004-05 increased by 42 per cent to Rs 1815 crore from Rs 1278 crore in the previous year. Several companies are spending more than 10 per cent of their revenues on R&D. The investment in R&D is always for long term and it takes longer time to generate profits. These investments are putting initial burden on working, but it is creating strong base for Indian companies.
Rapidly changing dynamics of the global pharmaceuticals industry and the pressure on global pharma players to lower the costs of medicines without compromising on quality is opening up new opportunities for Indian companies with a strong track record of IPR compliance and R&D capabilities.
India's leading companies, viz., Ranbaxy Laboratories, Cipla, Dr Reddy's Laboratories, Sun Pharmaceuticals, Lupin, Nicholas Piramal Torrent Pharma, Glenmark, Jubilant Organosys, Aurobindo Pharma, Cadila healthcare, Wockhardt, Orchid, Biocon, Ipca Laboratories ,Torrent Pharma, etc., are spending significant amount on R&D. The Indian firm's R&D efforts are mainly focusing on new drug discovery programme, New Drug Discovery Systems (NDDS), recombinant biopharmaceuticals, clinical research, etc.
Ranbaxy Laboratories, among the top 10 global generic player with growing presence in 23 of the top 25 pharma markets and the largest ANDA filers with US FDA, has realigned and strengthened its business units, and is actively pursuing various options to augment its global operations. The company is focusing more on in-licensing, co-marketing, as well as research collaborations in New Drug Discovery Research (NDDR). It has commenced state-of-the-art R&D centre for NDDR during 2005. The R&D expenditure for the year ended December 2005 increased by 47 per cent to Rs 486.36 crore from Rs 331.39 crore in the previous year.
The company introduced 49 new products and line extensions in India through its Pharma Research capabilities. The company filed 36 ANDAs with the US FDA, including 10 under the US President's Emergency plan for AIDS Relief (PEPFAR) programme. It received approvals for 19 ANDAs, including 3 under PEPFAR programme. Its cumulative ANDA applications reached at 183, with 114 approvals obtained and 69 pending approvals with US FDA. The company filed 131 DMFs during 2005.
Ranbaxy made 52 national filings for 46 product in 7 European Union Reference Member States and 51 Mutual Recognition Procedure applications for 6 products in 24 EU concerned member states. The company filed 110 products in emerging markets, comprising the Brazil, Russia, India, China, South Africa (BRICS) countries. Its pharmaceutical research team filed 35 patents in India.
Ranbaxy launched 4 new products in India in the area of Oral Controlled Release Systems of which 3 were developed in house and one was outsourced. The company filed three Novel Drug Delivery System (NDDS) based ANDAs with US FDA and four with European regulatory agencies. It filed 15 patents in the NDDS area in India. It is focusing on developing novel, patentable, safe and environment-friendly processes for the production of high quality APIs and it filed 68 patents in India.
The company has built significant expertise in NDDR, Novel Drug Delivery systems research, Pharmaceutical research and chemical & fermentation research. The company is pursuing 10 research programmes with the help of over 300 scientists in the therapeutic areas of infectious diseases, urology, metabolic diseases and rheumatoid arthritis.
Ranbaxy developed RBx 11160 molecule, a potential anti-malarial candidate, is under development in association with Geneva-based Medicines for Malaria Venture (MMV). This drug is a short-acting drug, which needs to be combined with another long acting drug, to comply with the current WHO guidelines for development of new anti-malarial compounds. The company identified Piperaquine phosphare as a synergistic partner for RBx 11160 and filed an investigational new drug application with Swiss medic during December 2005.
Ranbaxy completed phase I single and multiple rising dose studies in respect of RBx 9841 for urinary incontinence. The molecule is a potent and selective inhibitor of M3 (muscurinic) receptor. The molecule is also being investigated for other indications such as COPD and Asthma. In the area of infectious disease, it is working on a novel antibiotic to treat Community Acquired Respiratory Tract Infections (CARTI). It has undertaken two programmes with GlaxoSmithKline.
Ranbaxy is also taken a conscious decision to pool its resources to fight the neglected diseases of the developing nations. The company is undertaking research in collaboration with MMV, Geneva on an anti-malarial molecule. The AIDS epidemic today is unparalleled in the challenges it poses to the world and it is clearly an issue that no one can address alone. The company has successfully introduced high quality bio-equivalent, single dose and fixed dose generic Anti-retrovirals for HIV/ AIDS patients at affordable prices.
The company is also developing safe and effective herbal dugs that comply to international quality standards. It launched 2 products in the international market LEAV (a natural sweetener) in Malaysia and Revital Appetit (appetite enhancer for kids) in Romania. It also filed two products in Russia, Ukraine and Malaysia and it has seve-ral niche products under the over- the-counter category.
Cipla, a Rs 3000 crore Mumbai based pharma company, stepped up its R&D expenditure to Rs 155 crore during 2005-06 from Rs 98 crore in the previous year, a growth of more than 58 per cent. The company is focusing on developing and enhancing know-how for new drug delivery systems and manufacturing processes both for APIs and drug formulations. Cipla entered strategic alliance with Avestha Genegraine Technologies Pvt Ltd for the development of biotherapeutics.
The company introduced many drug formulations and active pharmaceutical ingredients (APIs) in the country. Some of the formulations have the unique distinction of being the first products of their kind in the world. The few important drugs like Imidara imiquimod cream) -topical immune response modifier for genital warts, Lopimune (iopinavir and ritonavir sofgelcaps) - combination protease inhibitor for HIV/AIDS, Bifilin (prebiotic and postbiotic capsules and sachet)- probiotic supplement received good response from the market.
The company's manufacturing facilities are approved by several regulatory bodies like US FDA, MHRA (UK), PIC (Germany), MCC (South Africa), TGA (Australia), Department of Health (Canada), ANVISA (Brazil), SIDC ( Slovak Republic), the Danish Medical Agency and the WHO. Its Kurkumbh plant has been certified for compliance with ISO 14001 and OHSAS 18001 standards.
Its R&D is mainly focusing on development of new drug formulations for existing and newer active dug substances. It is also looking into agrotechnology, genetics and biotechnology for cultivation of medicinal plants and isolation of active ingredients from plant materials. It is also undertaking projects to develop APIs and formulations jointly with overseas companies.
The company has entered into partnerships for 123 products with a number of partners in the USA alone. It filed over 170 registrations in Europe, principally for marketing its drug formulations in the continent. In addition, Cipla has approvals for over 4000 drug formulations in the emerging markets, including South & Central America, the Middle East and Africa.
Dr Reddy's Laboratories (DRL) has re-engineered its R&D activities and has built an even stronger pipeline for the future. It entered a deal in discovery research with Citigroup Venture and ICICI Venture to form an integrated drug development company called Perlecan Pharma Pvt Ltd. DRL has transferred all rights and titles of four discovery molecules in the area of cardiovascular and metabolic disorders.
DRL has also tie-up with Rheoscience A/S to co-partner the development of balaglitazone (DRF 2593) a partial PPR-gamma agonist for the treatment of Type 2 diabetes. This product is likely to move to phase III clinical trials. Further, its five key NCEs advanced to clinical development and few are in pre-clinical stage.
The company strengthen its generics and API pipeline. It filed 12 ANDAs during 2005-06, taking the total number of ANDAs filings to 70. Out of this, 49 ANDAs are pending with US FDA for approvals. The company filed 30 DMFs during 2005-06 and its total number of DMFs reached at 151 - 81 filed in the US, 28 in Canada and 42 in Europe.
DRL has been aggressively investing in expanding its pipeline of APIs and finished dosages. It is actively pursuing collaborative mechanisms in its discovery R&D. However, its R&D expenditure during the year ended March 2005-06 declined by 14.7 per cent to Rs 253.94 crore from Rs 297.79 crore in the previous year. The decrease in absolute value of R&D expenses was largely on account of lower costs in the Drug discovery and in Generics business segments.
Lupin Researh Park at Pune, sprawling across 19 acres with a built up area of 1.50 lakh sq.fts., housing 320 scientists, is the hub of all research initiatives undertaken by the company. It has attained capabilities to develop quality APIs at productivity levels rivalling the best, value added finished products in the generic space based on platform technologies. Its R&D activity is vertically integrated, starting from process development of the API till the submission of dossiers for finished dosages.
The company has identified cardiovascular and anti-diabetics as prominent growth drivers and focuses on them through a dedicated business division. Further, being a major player in TB drugs in the past, the company also entered various segments like anti-TB, anti-infective, anti-asthma, and CNS.
Lupin's R&D activities are moving in great earnest and right direction. It is playing a pivotal role in selecting and developing molecules that are being commercialized successfully. The achievement of this activity could be gauged from the volume and diversity of its filings. During the year 2005-06, the company filed 18 ANDAs in US, nine MAAs in UK, six MAAs in Australia, three MAAs in New Zealand, two MAAs in France, three MAAs in Croatia and 343 dossiers for the rest of the world. It has also filed 64 patents during the year. The NCE research progress is encouraging. Four investigational new drugs addressing three different disease areas viz. migraine, psoriasis and tuberculosis are in various phases of clinical development. Its NDDS initiatives are expected to open licensing opportunities in the near future.
The company's R&D expenditure reached at Rs 108 crore during the year ended March 2006 and worked out to 6.7 per cent of its total turnover. Successful transfers of technology to manufacturing plant and approval from regulatory bodies have resulted in commecialisation of several products particularly for the regulated markets. Several products are under various stages of regulatory approval process.exhibited IC50 of 2.7nM; over 3700 fold selectivity to PDE4, bioavailability >90% across species and a 10 hr half-life, thus indicating potential for a once daily dosing regimen. Additionally, there was no emesis in the pre-clinical models, good results in early toxicology studies, a good safety margin and it also exhibited good action on in-vivo RA and TNFá inhibition models. Clinical trials should be initiated in February 2007 and with 2012 as the targeted launch date.
GRC 10389, Cannabinoid-1 [CB-1] receptor antagonist, targeting obesity.This molecule has demonstrated high potency with IC50 of 14 nM and Ki[humans] of 11 nM. The compound showed >40% bioavailability across species tested and >300 fold selectivity over CB-2. Glenmark plans to start clinical trials in H1, FY07 and has set a target launch date of 2011.
Wockhardt Ltd continues to focus on R&D and the creation of successful IPRs. Through R&D and discovery of new drugs, the company also has the potential power to address unmet medical needs and improve the lives and health of millions of people across the globe. The pursuit of world-class quality has led to Wockhardt's manufacturing facilities receiving the approval of regulatory bodies such as the US FDA, MHRA, and WHO. The Wockhardt Biotech Park in India, received WHO certification during 2005 for both Wepox(r-erythropoietin) and Wosulin (r-insulin).
The company's R&D expenditure for the year 2005 increased to Rs 81.08 crore from Rs 71.49 crore in the previous year. This worked out 8.42 per cent of its total turnover.
Wockhardt's focus on biotehnology started adding to its revenue. It has developed comprehensive capabilities in all facets of recombinant biotechnology including gene cloning, development of production strains, development of expression systems in yeast, mammalian and bacterial cells. The company launched three new products in India for managing diabetes, cancer/kidney failure and preventing hepatitis-B infection. These are now being introduced in other markets too around the world. The biotechnology products have received 25 approvals from 18 countries, and more are in the pipeline. Its biopharmaceutical portfolio grew by 54 per cent during the year 2005.
Wockhardt decided to take the first steps in new drug discovery research and chose the anti-infective therapy. The company is in discussion with international pharmaceutical companies for future licensing opportunities for various molecules. The company is working on WCK 771, its proprietary compound, as a parenteral anti MRSA agent. This molecule concluded phase I human clinical trials during the year and entered the phase II 'proof of concept' stage. The company also launched Biovac A, a new generation hepatitis A vaccine in the Indian market, under licence from a leading Chinese biotechnology company.
Nicholas Piramal India Ltd, among the top ten Indian companies, is currently strengthen its R&D activity by appointing 350 scientists for long-term exploratory and applied research programmes in chemistry, biology and natural product chemistry dedicated to discovery and development of new drugs for the global market. The company increased the number of drug candidates in its preclinical and clinical development pipeline.
Its lead candidate, P-276-00 for cancer is undergoing phase I clinical trials in Canada and also received DCGI approval for start phase I trials in India. Its five pre-clinical candidates - four new chemical entities and one mono-herbal preparation have exhibited good progress during FY2006. The company's R&D expenditure declined to Rs 91.15 crore from Rs 108.44 crore in the previous year.
Biocon is committed to realizing the potential of biotherapeutics and it is rapidly transforming into an innovation-led organisation. The company made the single largest capital investment of Rs 650 crore in Biocon Park. This integrated biopharmaceutical hub meets international regulatory standards and represents a significant advancement in sophistication and automation. Its pipeline of discovery-led research products is both extensive and exciting. Its R&D expenditure increased to Rs 40.07 crore during the year ended March 2006 from Rs 24.09 crore in the previous year.
Biocon's innovation programme is built on in-house capabilities, proprietary technologies and a broad spectrum of global alliances. The custom and clinical research services improved its overall capabilities. The company is in the process of commercializing its first human monoclonal antibody BIOMAb-EGFR. It is also exploring strategic collaboration to co-develop recombinant therapeutics, antibodies and a host of in-licensed products.
The company is setting up new laboratories to facilitate expansion of its combined research activities. It is planning further investments in infrastructure for the biologics pilot plant to produce molecules for phase I and phase II clinical trials. The company filed 266 patent applications of which 76 are international PCT applications. It received 37 patents including 8 in USA.
The company incorporated two wholly owned subsidiaries viz., Syngene International Pvt Ltd and Clinigene International Pvt Ltd to undertake custom and clinical services. Syngene has initiated a programme to develop novel molecules based on a collaborative business model. Clinigene, its clinical research organization, is setting up huge facility for conducting internationally benchmarked clinical trials for MNCs.
Recently its subsidiary Syngene International and Innate Pharmaceuticals AB, Umea, Sweden entered collaboration agreement to jointly develop, manufacture and market virulence blockers to counteract bacterial diarrhoeal disease. Virulence blockers are a new class of drugs that could become an alternative to antibiotics.
Orchid Chemicals & Pharmaceuticals Ltd is consolidating its new drug discovery (NDD) research activities under a common umbrella. As part of this initiative, the company and Bexel Pharmaceuticals, Inc have reached an understanding by which the company would extend its ownership in Bexel from the current 74% to 100% for a cash consideration of US$ 3 million. .
Both companies believe that bringing all drug discovery activities under a unified structure will provide seamless integration of the several drug discovery programmes being pursued at the company and Bexel while retaining the advantages of having a discovery front-end in the US and a discovery cum developmental back-end at the company, Chennai. The company has already established a wholly owned subsidiary, Orchid Research Laboratories Ltd (ORLL), to channel its drug discovery work.
The arrangement involves buy-out by the company of the shareholding of the US founders of Bexel Pharmaceuticals for a cash consideration of US$ 3 million. The founders and key employees of Bexel would be granted 650,000 stock options as per standard Orchid ESOP guidelines, which they will subscribe at the grant price.
In an independent arrangement, Bexel would be providing an earn-out to the principal founder of Bexel in the event of an out-licensing deal for BLX-1002 materialising in a prescribed timeframe based on the phase II clinical trials that are planned. The managerial and scientific organization of Bexel will continue as an integral part of the new structure, providing continuity and commitment to the company's broader drug discovery thrust.
Bexel has been focusing on drug discovery research in metabolic diseases (such as diabetes, obesity and auto-immune diseases) while the company has been focusing on inflammation, cancer and anti-infective areas. Bexel's anti-diabetes molecule BLX-1002 has progressed the most among these, having completed phase I safety and tolerability studies in healthy human volunteers as well as safety and tolerability studies in diabetic patients.
The phase I human clinical trials conducted in 4 stages so far have been successful without any adverse side effects being seen. Besides glucose lowering in diabetic patients, the compound also showed additional benefit of lowering of triglycerides and hypertension. These and certain other studies recently completed suggest the need for extended human clinical trials to profile the benefits in different arms of patients.
Bexel and the company are now planning to conduct more elaborate phase II human clinical trials on BLX-1002 in the context of its efficacy in multiple indications. These will be conducted in two stages of a 28-day human clinical study followed by a 90-day study if necessary to generate significant additional data on the compound. These trials will be carried out under the Investigational Medicinal Product Dossier (IMPD) procedure in Europe. Other biological studies are being undertaken in parallel to identify the mechanisms of action in the context of efficacy in diabetes and related complications.