The Ghost Keeps Haunting: NCD Dogs Cancer in ‘Compulsory License’ Debate of India

Posted on March 11, 2013 by Tapan Ray

In November 2012, as a part of the ‘Campaign for Affordable Trastuzumab’ for the treatment of breast cancer, a citizens’ collective, reportedly sent an ‘Open Letter’ signed by around 200 cancer survivors, women’s groups, human rights and health rights campaigns and treatment activists from across the world to the Indian Prime Minister, urging him to ensure that the breast-cancer drug Trastuzumab is made affordable for treating cancer patients in the country.

Trastuzumab was named because of the following reasons:

Breast-cancer affects around 28-35 per cent of all cancers among women in major cities of India.

No other drug against HER+2 cancer can reduce patients’ mortality as Trastuzumab and reduce the spread of malignancy to other parts of the body.

Majority of women with HER+2 breast cancer do not have access to a complete course of the drug, which reportedly costs anywhere between Rs 6 to 8 lakhs (US$ 11,000 to US$ 14,500).

Reaping reach harvest:

According to a media report, three homegrown Indian companies are currently developing biosimilar drugs to this protein molecule to reap a reach harvest arising out of the emerging opportunities.

However, this is expected to be an arduous, expensive and challenging endeavor, as the concerned companies will require pursuing a complicated biotechnological route to create follow-on biologics for Trastuzumab.

The ‘Trigger Factor’:

It is widely believed that the above ‘Open Letter’ to the Prime Minister had prompted the Ministry of Health to form an ‘Experts Committee’ to evaluate the situation and make recommendations accordingly.

Thereafter, within a short period of time, in January, 2013, in a move that is intended to benefit thousands of cancer patients, Ministry of Health forwarded the report of the above ‘Experts Committee’ to the Department of Industrial Policy and Promotion (DIPP) for its consideration to issue Compulsory Licenses (CL) for three commonly used anti-cancer drugs namely, Trastuzumab (used for breast cancer), Ixabepilone (used for chemotherapy) and Dasatinib (used to treat leukemia). Public Health Foundation of India (PHFI), among other experts, also reportedly had participated as a member of this ‘Experts Committee’,

For a month’s treatment drugs like Ixabepilone and Dasatinib reportedly cost on an average of US$ 3,000 – 4,500 or Rs 1.64 – 2.45 lakh for each patient in India.

A ‘Technology Transfer’ discouraged:

Such a rapid development in the CL landscape of India is indeed intriguing, especially after a voluntary announcement by Roche in 2012 that it will produce Trastuzumab and Rituximab in India through transfer of technology to an Indian contract manufacturer.

Consequently for a month’s treatment, the price of Trastuzumab will come down from around US$ 2,000 to US$ 1, 366, i.e. by 31 percent and Rituximab from around US$ 1,456 to US$ 682 i.e. by 53 percent. This was reportedly announced by none other than the Minister of State of Chemicals and Fertilizers of India Mr. Srikant Jena.

Despite this voluntary decision of technology transfer and price reduction of two life saving drugs in India by Roche, reported Government consideration for grant of CL for Trastuzumab, without getting engaged in any form of a win-win dialogue with the Company, could ultimately prove to be counter productive and may discourage further technology transfer of expensive patented drugs to India.

Increasing incidence of cancer in India:

Cancer is just not a dreaded disease, but also making a devastating impact, financial and otherwise, on the lives and families of thousands of sufferers in India.

According to ‘The Lancet’, published on 28 March 2012, in India 556 400 people died of cancer only in 2010.

The paper also comments that only half of the estimated 9.8 million total deaths per year is captured by the CRS in India, fewer than 4 percent are medically certified, while more than 75 percent of deaths occur at home.

The Lancet study clearly highlights that most cancer patients in India die without medical attention and drugs. Cancer is, therefore, increasingly becoming a public sensitive disease area with high socioeconomic impact in the country. High treatment cost of this near terminal disease is beyond reach of majority of population in the country.

In a written reply to a question in the ‘Upper House’ of the Indian Parliament, the Minister of State for Health and Family Welfare on March 4, 2012 said that according to “Three Year Report on Population Based Cancer Registries 2006 – 08″ of the Indian Council of Medical Research (ICMR), the estimated numbers of cancer patients for 2015 and 2020 are 1.16 million and 1.27 million respectively. There is a gradual rise in the prevalence of cancer in India, though the government has initiated several measures in this area.

High incidence of breast cancer:

As per a recent report, an estimated 1, 00,000 – 1, 25,000 new patients suffer from breast cancer every year in India and this number is expected to double by 2025.

Government is mulling CL for NCD:

Currently the DIPP appears to be planning to extend the provision of Compulsory License (CL) beyond cancer drugs to other Non-Communicable Diseases (NCD) in the country, like diabetes.

Domestic Pharma Association supports the move:

A major domestic pharmaceutical industry association, as per media reports, supports this move by clearly articulating, “Over the years, more deaths are taking place on account of Non-Communicable Diseases (NCDs) than communicable ones. It is, therefore, natural that this provision (CL) will be used for NCDs as well.”

UN declaration on NCD provides flexibilities in TRIPS Agreement:

Experts believe that this new move on CL for drugs related to NCDs is a consequence of India’s signing the United Nation (UN) declaration on the prevention of NCDs in the country by, among others, using flexibilities in the TRIPS Agreement to increase availability of affordable drugs for such diseases.

The Government has already launched a “National Program for Prevention & Control of Cancer, Diabetes, Cardio Vascular Diseases and Stroke (NPCDCS)” as a pilot project covering 150 million people in 100 inaccessible and most backward districts during the financial year 2011-2012 at a cost of US$ 275 million.

Socio-economic impact of NCDs in India:

Indian Journal of Community Medicine (IJCM) in an article titled, “Social and Economic Implications of Non-Communicable Diseases (NCDs) in India” has highlighted, among others as follows:

NCDs account for 62 percent of the total disease burden in India with a significant ascending trend both in terms of overall mortality and morbidity.

This burden is likely to increase in the years to come.

Due to chronic nature of the disease and technological advancements in care, costs of treatment are high leading to access barriers, or ‘catastrophic expenditures’ for those who undergo treatment.

There are evidences of greater financial implications for the poorer households suffering from NCDs.

Most estimates suggest that the NCDs in India account for a significant economic burden ranging from 5 to 10 percent of GDP.

An urgent multi-sectoral Government action is strongly warranted both on grounds of economic arguments and social justice.

Action needs focus on addressing the social determinants of NCDs for prevention and strengthening of health systems to meet the challenge.

A framework for monitoring, reporting, and accountability is essential to ensure that the returns on investments in NCDs meet the targets and expectations set in the national plans.

Innovator companies contemplating legal recourse:

Reacting to all these developments, the global pharmaceutical companies have, once again, expressed strong commitment to protect and continue to defend their Intellectual Property Rights (IPR) within the legal framework of India.

They have also reiterated their belief that a robust IPR regime will encourage innovation in the country making available more and more innovative drugs for the patients in India.

An interesting WHO report on a ‘robust IPR regime’:

In this regard a World Health Organization (WHO) research report titled “Patents, Price Controls and Access to New Drugs: How Policy Affects Global Market Entry” makes some interesting observations on a ‘robust IPR regime’.

The report highlights the following four important points:

1. Increasing the strength of a patent system to include long-term protection on pharmaceutical products appears to spur market entry mostly in the high-income countries.

For the low- and middle-income countries that are currently being encouraged to move to stronger protection through trade policies, the evidence that extending protection enhances access to new pharmaceuticals is mixed.

2. There is some evidence that high level of protection might encourage more frequent entry of innovative products in the short term. However, in the longer term the same domestic capacity could well be an alternative source of entry of such drugs.

3. Intellectual Property (IP) holders frequently assert that the poor quality of enforcement in developing countries undermines the value of their patent rights. However, it is quite evident now that patent laws in these countries are at least broadly meaningful commensurate to their respective domestic requirements.

4. The standard argument on price regulation that it will dissuade market entry for innovative drugs appears to have more relevance among the high-income countries and not so for the poorer countries.

The authors further indicate:

“There we find that while price regulation makes it less likely that new drugs will be available quickly, it does not appear to prevent new products from being launched eventually.”

Conclusion:

Following all these recent developments and weighing pros and cons, one could well imagine that pressure on the Government from various stakeholders for CL on drugs for Cancer and NCDs will keep mounting, unless an alternative measure like, ‘Price Negotiation for Patented Drugs’ is put in place by the Department of Pharmaceuticals, sooner than later, in 2013.

The recent judgment of the ‘Intellectual Property Appellate Board (IPAB)’ on CL to Natco may further add fuel to this raging debate.

It is now quite clear from the Finance Minister’s speech on the ‘Union Budget Proposal’ for 2013-14 that eagerly awaited ‘Universal Health Coverage’ or ‘Free Distribution of Essential Medicines to all’ schemes will not be implemented, at least for now.

Thus in all probability, the ghost of CL will keep haunting the innovators in India unabated, unless an effective, scalable and sustainable model for improving access to patented drugs for majority of population in the country is put in place. This will call for demonstrative, innovative and constructive Public-Private-Partnership (PPP) initiatives, sooner. In this effort all concerned should at first be aligned with the cause, in principle, and try to be a constructive partner to get it translated into reality together, rather than just playing the role of vociferous critics in perpetuity .

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Takes ‘Two to Tango’: Encashing Opportunities with Biologic drugs in India

Posted on February 11, 2013 by Tapan Ray

Despite current ‘Patent Cliff’ ongoing research on biologics is now at the forefront of the Global Pharmaceutical Industry. The bottom-line impact of a successful new biologic molecule to treat intractable ailments like, cancer, blood disorders, Parkinson’s, Myasthenia Gravis, Multiple Sclerosis, Alzheimer’s diseases, will be huge.

Currently, faster growth of this segment as compared to conventional small molecules is primarily driven by novel technologies and highly targeted approaches, the final outcome of which is being more widely accepted by both physicians and patients.

Lesser generic competition makes it more attractive:

After patent expiry, innovators’ small molecule brands become extremely vulnerable to cut throat generic competition with as much as 90% price erosion.This is mainly because these small molecules are relatively easy to replicate by many generic manufacturers and the process of getting their regulatory approval is also not as stringent as biosimilar drugs in most of the markets of the world.

On the other hand biologic drugs involve difficult, complex and expensive processes for development. Such resource intensive scientific expertise together with stringent regulatory requirements for obtaining marketing approval, especially in the developed markets of the world like, EU and USA, help creating a significant market entry barrier for many players. That is why even after patent expiry, biologics enjoy significant brand protection from generic competition for quite some time, in many cases.

It is for this reason brands like the following ones are expected to go relatively strong even for some more time, without any significant competition from biosimilar drugs in many of the major markets of the world:

Brand	Company	Launch date
Rituxan	Roche/Biogen idec	1997
Herceptin	Roche	1998
Remicade	Centocor/J&J	1998
Enbrel	Amgen/Pfizer	1998

Global Market:

In 2011 the turnover of Biologic drugs increased to over US$ 175 billion in the total market of US$ 847 billion. The sale of Biosimilar drugs outside USA exceeded US$ 1 billion.

Six biologic drugs featured in the top 10 best selling global brands in 2012 with Humira of AbbVie emerging as the highest-selling biologics during the year. Roche remained the top company by sales for biologics with anticancer and monoclonal antibodies.

According to IMS Health, by 2015, sales of biosimilars are expected to reach between US$ 1.9 – 2.6 billion, an increase from US$ 378 million for the year to the first half of 2011.

Attractiveness:

The answer to the key question of why do so many companies want to enter into the biotech space of the business, in summary, could lie in the following:

Truly innovative small molecule discovery is becoming more and more challenging and expensive with the low hanging fruits already being plucked.
More predictable therapeutic activity of biologics with better safety profile.
Higher percentage of biologics have turned into blockbuster drugs in the recent past.
Market entry barrier for biosimilar drugs, after patent expiry of the original molecule, is much tougher than small molecule generics.
A diverse portfolio of both small and large molecules will reduce future business risks.

A 2012 report by PwC titled ‘From Vision to Decision: Pharma 2020’ states that “the next few years may look bleak for pharma, but we’re convinced that the following decade will bring a golden era of renewed productivity and prosperity.”

The document also points out that the global pharmaceutical industry is now focusing its R&D initiatives on biologics for the treatment of cancer and rare diseases. Nearly 30 percent of the 7,891 molecules currently in clinical testing cover cancer and autoimmune conditions.

Another emerging opportunity:

As stated above, unlike commonly used ‘small molecule’ drugs, ‘large molecule’ biologics are developed from living cells using very complex processes.

It is virtually impossible to replicate these protein substances, unlike the ‘small molecule’ drugs. One can at best develop a biologically similar molecule with the application of high degree of biotechnological expertise. These drugs are known as ‘Biosimilar Drugs’ and usually cost much less than the original ones.

Biosimilar drugs market is currently fast evolving across the world with varying degree of pace and stages of developments. The U.S currently holds the leadership status in the production of biologics, with around 45 percent of the total share. India’s share, now being at 7 percent is continuously increasing.

Biosimilar Monoclonal Antibodies (mAbs) in the Pipeline:

Company	Location	Biosimilar mAbs	Development Status
BioXpress	Switzerland	16	Preclinical
Gene Techno Science	Japan	6	Preclinical
Zydus Cadilla	India	5	Preclinical
PlantForm	Canada	3	Preclinical
BioCad	Russia	3	Preclinical
Celltrion	South Korea	2	Phase 3
LG Life Sciences	South Korea	2	Preclinical
Gedeon Richter	Hungary	2	Preclinical
Cerbios-Pharma	Switzerland	1	Preclinical
Hanwha Chemical	South Korea	1	Preclinical
PharmaPraxis	Brazil	1	Preclinical
Probiomed	Mexico	1	Phase 3
Samsung BioLogics	South Korea	1	Preclinical
Novartis	Switzerland	1	Phase 2
Teva	Israel	1	Phase 2
Zenotech	India	1	Phase 3
Spectrum	US	1	Preclinical
Biocon/Mylan	India/US	1	Preclinical

(Source: PharmaShare; as of September 10, 2011 from Citeline’s Pipeline database)

Future business potential with cost arbitrage of India:

In 2013, products like, Avonex of Biogen Idec, Humalog of Eli Lilly, Rebif of Merck KgaA, Nupugen of Amgen will go off-patent, paving the way of entry for lower priced biosimilar drugs. The sum total of revenue from all such drugs comes to over U.S$ 15 billion.

The report from the ‘Business Wire’ highlights that, ‘the manufacture and development of a biosimilar molecule requires an investment of about US$ 10 to 20 million in India, as compared to US$ 50 to 100 million in developed countries’, vindicates the emergence of another lucrative business opportunity for India for such drugs with significant cost arbitrage.

Government support in India:

In India, the government seems to have recognized that research on biotechnology has a vast commercial potential for products in human health, including biosimilars, diagnostics and immunobiologicals, among many others.

To give a fillip to the Biotech Industry in India the National Biotechnology Board was set up by the Government under the Ministry of Science and Technology way back in 1982. The Department of Biotechnology (DBT) came into existence in 1986. The DBT currently spends around US$ 300 million annually to develop biotech resources in the country and has been reportedly making reasonably good progress.

The DBT together with the Drug Controller General of India (DCGI) has now prepared ‘Regulatory Guidelines for Biosimilar Drugs’ in conformance to international quality and patient safety standards.

Currently, a number of both financial and non-financial incentives have been announced by the Central and the State Governments to encourage growth of the biotech industry in India, which include tax incentives, exemption from VAT and other fees, grants for biotech start-ups, financial assistance with patents, subsidies on investment from land to utilities and infrastructural support with the development of ten biotech parks through ‘Biotechnology Parks Society of India’.

A commendable DBT initiative:

Towards this direction, the Department of Biotechnology (DBT) of the Government of India has taken a commendable step to encourage the small and medium scale business outfits by setting-up ‘The Small Business Innovation Research Initiative (SBIRI)’. This scheme has been launched to boost ‘Public-Private-Partnership (PPP)’ projects in the country.

SBIRI supports ‘the high-risk pre-proof-of-concept research’ and ‘late stage development’ in small and medium size companies to get them involved in the development of biologics.

Some examples:

Examples of some among many of the PPP initiatives in the healthcare space under SBIRI are as follows:

No.	Company Name with Collaborator	Title of the Project Supported
1.	IcubedG Ideas Private Limited, New Delhi	Risk based Process Design for large scale Manufacturing of male injectable contraceptive (Phase I)
2.	Incozen Therapeutics Pvt. Ltd., Hyderabad	Discovery and Development of Novel, Selective and Potent Dihydroorotate Dehydrogenase Inhibitors in Inflammatory Bowel diseases. (Phase I)
3.	Mediclone Biotech Private Limited, Chennai	Commercial Production of Monoclonal Antibodies as an import substitute with special reference to Red Blood Cell Phenotyping (Phase II)
4.	Orchid Chemicals & Pharmaceuticals Ltd., Chennai in collaboration with AU-KBC Research Center, Chennai	Development and validation of a cell-tissue co-culture model for aiding liver specific studies and drug discovery applications. (Phase I)
5.	Reliance Life Sciences Pvt. Ltd., Navi Mumbai	An open label, multicenter, prospective clinical study to evaluate the safety and efficacy of tissue engineered R-STE-001 in patients with symptomatic cartilage defect of femoral condyle (Phase II)
6.	USV Limited, Mumbai	Development of a Vaccine capable for eliciting immunological memory for the prevention of Typhoid (Phase II)
7.	Virchow Biotech Private Limited, Hyderabad	Development of commercialization of a recombinant uricase for the prevention and treatment of tumor lysis syndrome associated with leukemia, lymphoma & solid tumor malignancies (Phase II)
8.	Virchow Biotech Private Limited, Hyderabad	Indigenous development of a recombinant Fuzeon for the treatment of AIDS (Phase II)
9.	Zenotech Laboratories Limited., Hyderabad	Development of humanized monoclonal antibodies against human epidermal growth factor receptor (Phase I)


10.	Advanced Neuro-Science Allies Pvt. Ltd, Bangalore in collaboration with Vittal Mallya Scientific Research Foundation, Bangalore	Pre-clinical studies of Human mesenchymal stem cells (MSCs) isolated and characterized from different sources in autoimmune disease, namely rheumatoid arthritis (RA) and type 1 diabetes (TIDM)(Phase I)
11.	Avesthagen Ltd., Bangalore	Hepatocyte-like cells generated from human embryonic stem cells (hESC) for hepatotoxicity screening of xenobiotics in the drug discovery process(Phase I)
12.	Avesthagen Limited, Bangalore	Scale-up and evaluation of high-value biosimilar product (Etanercept) aimed at providing cost-effective healthcare solutions to the emerging markets(Phase II)
13.	Bharat Serum and Vaccines Limited, Mumbai	Expression of recombinant proteins for development of synthetic pulmonary surfactant for Respiratory Distress Syndrome(Phase I)
14.	Cadila Pharmaceuticals Ltd., Ahmedabad	Development of Mycobacterium was an adjuvant for anti – rabies vaccine(Phase I)

Besides, Indian pharmaceutical majors like Dr. Reddy’s Laboratories (DRL), Reliance Life Science, Shantha Biotech, Ranbaxy, Biocon, Wockhardt and Glenmark have made good investments in biotech drugs manufacturing facilities keeping an eye on the emerging opportunities with Biosimilar drugs in the developed markets of the world.

Funding remains a critical issue:

That said, many industry experts do feel that R&D funding for the Biotech sector in the country is grossly inadequate. Currently, there are not many ‘Venture Capital’ funds for this sector and ‘Angel Investments’ almost being non-existent, Indian biotech companies are, by and large, dependent on Government funding.

Making India a global hub for biosimilar manufacturing:

However, with around 40 percent cost arbitrage, adequate government support and without compromising on the required stringent international regulatory standards, the domestic ‘biologic’ players should be able to establish India as one of the most preferred manufacturing destinations to meet the global requirements for particularly ‘biosimilar drugs’.

Experience in conforming to stringent US FDA manufacturing standards, having largest number of US FDA approved plants outside USA, India has already acquired a clear advantage in manufacturing high technology chemical based pharmaceutical products in India. Significant improvement in conformance to Good Clinical Practices (GCP) standards will offer additional advantages.

Conclusion:

With increasing support from the government and fueled by creative, scientific and technological inputs from various experts and entrepreneurs in the country, India has the potential to emerge as one of Asia’s best powerhouses in the field of biosimilars drugs by the end of this decade. It will take ‘two to tango’.

By: Tapan J. Ray

Robust implementation of Biosimilar Guidelines could help India earn leadership status in ‘Biosimilar World’

Posted on November 5, 2012 by Tapan Ray

Across the world, biologic drugs, in general, have a successful record in treating many life threatening and other complicated ailments. Expiration of product patents of the first major group of originators’ biologic molecules has led to the development of products that are designed to be ‘similar’ to the originators’ products, as it is virtually impossible to replicate any protein substances, unlike the ‘small molecule’ drugs.

These are known as ‘Follow-on Biologics’ or more commonly ‘Biosimilar Drugs’, which rely in part, on prior information obtained from the innovators’ products and demonstration of similarity with the originator’s molecule based on detailed and comprehensive product characterization, for their marketing approval.

The bedrock:

India seems to have a good potential to become one of the key players in the development and manufacture of biosimilar drugs, not only to serve the needs of the local population, but also for exports to large developed and other developing markets. However, for this dream to materialize science-driven ‘Biosimilar Guidelines’ are absolutely necessary and should form the bedrock in the development process of all such drugs.

Paving the way:

These guidelines will provide a regulatory framework or pathway to ensure that biosimilar Drugs approved in India are of good quality and demonstrably similar in efficacy, safety and immunogenicity to the original reference products.

Paving the way for such regulatory framework in the country with comprehensive sets of guidelines is of utmost importance, especially in the light of prevailing sub-optimal pharmacovigilance system in India.

Setting ground rules:

Considerable developments have occurred across the globe in the scientific and regulatory understanding of biosimilar drugs. Nearly all developed nations and many developing countries have now defined or in the process of defining appropriate regulatory framework for the same.

However, due to lack of such guidelines in India, until recently, there have been instances of so called ‘biosimilar drugs’ being approved for marketing, reportedly with sub-optimal testing and dossiers, thereby putting into question the product quality, comparability and patient safety.

With the above backdrop, the Ministries of Health & Family Welfare and the Science and Technology have now set the ground rules and released India’s first “Guidelines on Similar Biologics: Regulatory Requirements for Marketing Authorization in India”. These Guidelines are already in place effective September 15, 2012.

A step in the right direction:

Long awaited new ‘Biosimilar Guidelines’ of India, demonstrating an overall similarity in the philosophy and approach with the those in the U.S and Europe, though a belated move by the Government, but certainly a step in the right direction.

The global potential:

In most of the developed countries, besides regulatory issues, biosimilar drugs are considered to be a threat to fast growing high value innovative global biotech industry.

At the same time, there is an urgent need to effectively address the global concern for cheaper and more affordable biologic medicines for patients across the world. To achieve this objective, relatively smaller biotech companies, given the required wherewithal at their disposal, could emerge as winners in this new ball game as compared to traditional generic pharmaceutical players.

Biosimilar drugs will, therefore, have immense global potential to improve access to life saving biologic medicines for the ailing population across the continents.

First ‘Biosimilar drug’ in the US:

Having received the US-FDA approval, the CEO of Sandoz had then commented, “The FDA’s approval is a breakthrough in our goal of making high-quality and cost-effective follow-on biotechnology medicines like Omnitrope available for healthcare providers and patients worldwide”.

Despite this event, very few people at that time expected the US FDA to put regulatory guidelines in place for approval of ‘Biosimilar drugs’ in the largest pharmaceutical market of the world.

Global initiatives:

Internationally most known companies in the biosimilar drugs space are Teva, Stada, Hospira and Sandoz. Other large research based global innovator pharmaceutical companies, which so far have expressed interest in the field of biosimilar drugs are Pfizer, Astra Zeneca, Merck and Eli Lilly.

Following are the examples of some relatively recent biosimilar drug related initiatives of the global players:

Merck announced its entry into the biosimilar drugs business on February 12, 2009 with its acquisition of Insmed’s portfolio for US$ 130 million in cash. The company also paid US$ 720 million to Hanwha for rights to its copy of Enbrel of Amgen
Samsung of South Korea has set up a biosimilars joint venture with Quintiles to create a contract manufacturer for biotech drugs.
Celltrion and LG Life Sciences have expressed global ambitions in biosimilar drugs.

According to Reuter (June 22, 2011), Merck, Sandoz, Teva and Pfizer are expected to emerge stronger in the global biosimilar market, as we move on.

In India:

Dr Reddy’s Laboratories (DRL) has already been marketing a biosimilar version of Rituxan of Roche since 2007.
Reliance Life Science is also a potential player in the biosimilar market, though it has reportedly faced a setback in Europe with the regulators asking for more data for its version of EPO prompting them to withdraw their application for now.

Many other developments are also taking place in tandem in the space of biosimilar drugs, the world over. To fetch maximum benefits out of this emerging opportunity, as mentioned above, India has already started taking steps to tighten its regulatory process for marketing approval of such drugs. This is absolutely necessary to allay general apprehensions on drug safety with inadequate clinical data for similar protein substances.

The global market:

According to Datamonitor the global market for biosimilars drugs is expected to grow from US$ 243 million in 2010 to around US $3.7 billion by 2015.

Another report points out that only in the top two largest pharmaceutical markets of the world, the USA and EU, sales of biosimilar drugs will record a turnover of US$ 16 billion in the next couple of years when about 60 biotech products will go off-patent.

Major Indian players:

Such a lucrative business opportunity in the western world is obviously attracting many Indian players, like, Biocon, Dr. Reddy’s Labs, Ranbaxy, Wockhardt, Shantha Biotech, Reliance Life Science etc., who have already acquired expertise in the development of biosimilar drugs like, erythropoietin, insulin, monoclonal antibodies, interferon-alpha, which are not only being marketed in India, but are also exported to other non/less-regulated markets of the world.

Ranbaxy in collaboration with Zenotech Laboratories is engaged in global development of Granulocyte Colony-Stimulating Factor (GCSF) formulations. Wockhardt is expected to enter into the global biosimilar drugs market shortly. Dr. Reddy’s Laboratories and Biocon are also preparing themselves for global development and marketing of insulin products, GCSF and streptokinase formulations.

The domestic market:

According to IMS Health March 2012, the biosimilar drugs market in India is around US$ 700 million with the main categories being as follows:

Therapy Area	US $ Million
Insulin	250
Hepatitis-B Vaccine	200
Heparin	70
Human Chorionic Gonadotropin	50

Moreover, as per available reports, till March 2012 about 91 clinical trials have been lined-up in India for 20 recombinant therapeutics, as approved by the Genetic Engineering Approval Committee.

Brand proliferation offering wider choices:

Currently there has been huge brand proliferation for biosimilar products in India with around 250 brands in 20 therapeutic areas. Some examples are as follows:

Therapy Area	No. of Brands
Insulin	40
Erythropoietin	55
Human Chorionic Gonadotropin	48
Streptokinase	33
Interferon	10
Heparin	10

Increasing demand:

The demand of such drugs even in India is increasing at a rapid pace. The focus of the government on various immunization programs is also getting sharper simultaneously. For example, during 2011-12, the government spent around US$ 115 million for routine immunization covering reportedly about 25 million pregnant women and children and nearly US$ 140 million towards pulse polio vaccination initiatives. This trend, though may not still be enough for the size and scale of a country like India, but praiseworthy nonetheless.

The focus on Oncology:

Within bio-pharmaceuticals many companies are targeting Oncology disease area, which is estimated to be the largest emerging segment with a value turnover of over US$ 55 billion in 2010 growing over 17%.

As per recent reports about 8 million deaths take place all over the world every year only due to cancer. May be for this reason, the research pipeline for NMEs is dominated by oncology with global pharmaceutical majors’ sharp R&D focus and research spend being on this particular disease area.

About 50 NMEs for the treatment of cancer are expected to be launched in the global markets by 2015.

Indian market for oncology products:

Current size of the Indian oncology market is reportedly around US$ 75 million.

Biocon has launched its monoclonal antibody based drug BIOMAb-EGFR for treating solid tumors with intent to introduce this product in the western markets as soon as they can get necessary regulatory approvals. Similarly, Ranbaxy with its strategic collaboration with Zenotech Laboratories is planning to market oncology products in various markets of the world like, Brazil, Mexico, CIS and Russia.

Government support:

It has been reported that the Department of Biotechnology (DBT) of the Government of India has proposed funding of US$ 68 million for biosimilar drugs through Public Private Partnership (PPP) initiatives, where soft loans will be made available to the Indian biotech companies for the same.

Currently DBT spends reportedly around US$ 200 million annually towards biotechnology related projects.

Areas of concern:

According to a research report from ‘The Decision Resources’, one of the key success factors for any such new biosimilar drugs, especially from India, will be how quickly the specialists accept them.

The report also noted a high level of concerns, if such drugs are not supported by robust sets of clinical data on the claimed treatment indications. To allay this concern robust implementation of the recent biosimilar guidelines in India will play a very critical role.

Conclusion:

As the R&D based global innovator companies are expanding into the biosimilar space, many Indian domestic pharmaceutical companies are also poised to invest on biosimilars drugs development to fully encash the emerging global opportunities in this area. It is quite prudent for the Indian players to focus on the oncology therapy area, as it has now emerged as the fastest growing segment in the global pharmaceutical industry.

With around 40 percent cost arbitrage and without compromising on the required stringent national and international regulatory standards, the domestic biosimilar players should be able to establish India as one of the most preferred manufacturing destinations to meet the global requirements for biosimilar drugs.

Experience in conformance to stringent US FDA manufacturing standards having largest number of US FDA approved plants outside U.S, India has already acquired a clear advantage in manufacturing high technology chemical based pharmaceutical products in India.

Having progressed thus far, with adequate additional investments for similar biologics and ensuring robust implementation of new ‘Biosimilar Guidelines’, India has the potential to earn the leadership status even in the global biosimilar segment, just as it did in the generic pharmaceutical space of the world.

By: Tapan J Ray

Getting unfolded a global opportunity for India with Biosimilar Drugs

Posted on December 19, 2011 by Tapan Ray

Over a period of time, the trend of a disease treatment process is becoming more targeted and personalized to improve effectiveness of both diagnosis and treatment. Biotechnology being the key driver to this trend, India should not fall out of line from this direction.

There are two clear opportunities for India in this fast evolving arena. One is to get more engaged in the discovery research of new large molecular entity and the other is to make a successful foray in the fast emerging and relatively high value biosimilar drugs (generic versions of biotechnology medicines) markets of the world.

In my view, India has greater probability of success in the field of biosimilar drugs, which could catapult India as a major force to reckon with in the fast growing biotechnology space of the global pharmaceutical industry.

An interesting global collaboration:

On October 19, 2010, the home grown Biotech Company Biocon with its headquarter in the Information Technology (IT) heartland of India – Bangalore created a stir in the Industry by inking an interesting international business deal with the largest global pharmaceutical company – Pfizer.

With this deal of US $350 million Biocon initiated its foray into the global biosimilar market by enabling Pfizer to globally commercialize Biocon’s biosimilar human recombinant insulin and three insulin analogues.

Before this deal, Sanofi-Pasteur, the’ vaccine business unit’ of the global major Sanofi of France had acquired Shantha Biotechnics, located in Hyderabad for a consideration of US$ 602 million, in July 2009.

Global players signal a new aspiration:

Just a year before the above acquisition in India, on December 11, 2008, Reuters reported that just two days after Merck announced a major push into biosimilar medicines, Eli Lilly signaled similar aspirations. This report, at that time, raised many eyebrows in the global pharmaceutical industry, as it was in the midst of a raging scientific debate on the appropriate regulatory pathways for biosimilar drugs globally.

Be that as it may, many felt that this announcement ushered in the beginning of a new era in the pharmaceutical sector of the world, not just for the pharmaceutical players, but also for the patients with the availability of affordable lower priced biologic medicines.

The scenario is heating up with regulatory hurdles relatively easing off:

Within the developed world, European Union (EU) had taken a lead towards this direction by putting a robust system in place, way back in 2003. In the US, along with the recent healthcare reform process of the Obama administration, the regulatory pathway for biosimilar drugs is now being charted out by the US FDA. However, as of November 2011, they do not seem to have finalized the details of the process.

It is worth mentioning that during the same reform process a 12 year data exclusivity period has been granted for biosimilar drugs, against the 5-year period of the same granted to the innovators of small molecule chemical drugs.

In the recent past, the EU has approved Sandoz’s (Novartis) Filgrastim (Neupogen brand of Amgen), which is prescribed for the treatment of Neutropenia. With Filgrastim, Sandoz will now have 3 biosimilar products in its portfolio.

The trigger factor:

Globally, the scenario for biosimilar drugs started heating up when Merck announced that the company expects to have at least 5 biosimilars in the late stage development by 2012. The announcement of both Merck and Eli Lilly surprised many, as the largest pharmaceutical market of the world – the USA, at that time, was yet to approve the regulatory pathway for biosimilar medicines.

What then are the trigger factors for the research based global pharmaceutical companies like Pfizer, Sanofi, Merck and Eli Lilly to step into the arena of biosimilar medicines? Is it gradual drying up research pipeline together with skyrocketing costs of global R&D initiatives, cost containment pressures from the payers or relatively strong market entry barrier for smaller players? I reckon, all of these.

Low penetration of lower cost biosimilar drugs:

Although at present over 150 different biologic medicines are available globally, just around 11 countries have access to low cost biosimilar drugs, India being one of them. Supporters of biosimilar medicines are indeed swelling as time passes by.

It has been widely reported that the cost of treatment with innovative and patented biologic drugs can vary from US$ 100,000 to US$ 300,000 a year. A 2010 review on biosimilar drugs published by the Duke University highlights that biosimilar equivalent of such biologics could not only reduce the cost of treatment, but would also improve access to such drugs significantly for the patients across the globe. (Source: Chow, S. and Liu, J. 2010, Statistical assessment of biosimilar products, Journal of Biopharmaceutical Statistics 20.1:10-30)

At present, the key global players are Sandoz (Novartis), Teva, BioPartners, BioGenerix (Ratiopharm) and Bioceuticals (Stada). With the entry of pharmaceutical majors like, Pfizer, Sanofi, Merck and Eli Lilly, the global biosimilar market is expected to heat up and develop at a much faster pace than ever before. Removal of regulatory hurdles (ban) for the marketing approval of such drugs in the US , as mentioned above, will be the key growth driver.

Biosimilar Monoclonal Antibodies (mAbs) in the Pipeline:

Company	Location	Biosimilar mAbs	Development Status
BioXpress	Switzerland	16	Preclinical
Gene Techno Science	Japan	6	Preclinical
Zydus Cadilla	India	5	Preclinical
PlantForm	Canada	3	Preclinical
BioCad	Russia	3	Preclinical
Celltrion	South Korea	2	Phase 3
LG Life Sciences	South Korea	2	Preclinical
Gedeon Richter	Hungary	2	Preclinical
Cerbios-Pharma	Switzerland	1	Preclinical
Hanwha Chemical	South Korea	1	Preclinical
PharmaPraxis	Brazil	1	Preclinical
Probiomed	Mexico	1	Phase 3
Samsung BioLogics	South Korea	1	Preclinical
Novartis	Switzerland	1	Phase 2
Teva	Israel	1	Phase 2
Zenotech	India	1	Phase 3
Spectrum	US	1	Preclinical
Biocon/Mylan	India/US	1	Preclinical

(Source: PharmaShare; as of September 10, 2011 from Citeline’s Pipeline database)

Global Market Potential:

According to a study (2011) conducted by Global Industry Analysts Inc., worldwide market for biosimilar drugs is estimated to reach US$ 4.8 billion by the year 2015, the key growth drivers being as follows:

Patent expiries of blockbuster biologic drugs
Cost containment measures of various governments
Aging population
Supporting legislation in increasing number of countries
Recent establishment of regulatory guidelines for biosimilars in the US

On the other hand, according to Alan Shepard, principal of Thought Leadership, Global Generics at IMS Health: ‘Forecasting biosimilar sales is complex because of various factors including the imprecise classification of a biosimilar and pricing policies of the originator resulting in the use of the brand in place of the biosimilar. Some estimates show the market growing from US$ 66 million in 2008 to US$ 2.3 billion in 2015. Others see sales exceeding US$ 5.6 billion in 2013. Whatever the forecast, there remains a US$ 50 billion potential for biosimilars’.

Currently, off-patent biologic blockbusters including Erythropoietin offer an excellent commercial opportunity in this category. By 2013, about 10 more patented biologics with a total turnover of around U.S. $ 15 billion will go off-patent, throwing open even greater opportunity for the growth of biosimilar drugs globally.

The scenario and business potential in India:

The size of biotech industry in India is estimated to be around US$ 4 billion by 2015 with a scorching pace of growth driven by both local and global demands (E&Y Report 2011). The biosimilar drugs market in India is expected to reach US$ 2 billion in 2014 (source: Evalueserve, April 2010).

Recombinant vaccines, erythropoietin, recombinant insulin, monoclonal antibody, interferon alpha, granulocyte cell stimulating factor like products are now being manufactured by a number of domestic biotech companies like Biocon, Panacea Biotech, Wockhardt, Emcure, Bharat Biotech, Serum Institute of India, Dr. Reddy’s Laboratories (DRL) etc.

The ultimate objective of all these Indian companies will be to get regulatory approval of their respective biosimilar products in the US and the EU either on their own or through collaborative initiatives.

Indian players are making rapid strides:

Biosimilar version of Rituxan (Rituximab) of Roche used in the treatment of Non-Hodgkin’s lymphoma has already been developed by DRL in India. Last year Rituxan clocked a turnover of over US$ 2 billion. DRL also has developed Filgastrim of Amgen, which enhances production of white blood-cell by the body and markets the product as Grafeel in India. Similarly Ranbaxy has collaborated with Zenotech Laboratories to manufacture G-CSF.

On the other hand Glenmark reportedly is planning to come out with its first biotech product by 2011 from its biological research establishment located in Switzerland.

Indian pharmaceutical major Cipla reportedly has invested Rs 300 crore in 2010 to acquire stakes of MabPharm in India and BioMab in China and is planning to launch a biosimilar drug in the field of oncology by end 2012.

In June this year another large pharmaceutical company of India, Lupin signed a deal with a private specialty life science company NeuClone Pty Ltd of Sydney, Australia for their cell-line technology. Lupin reportedly will use this technology for developing biosimilar drugs in the field of oncology, the first one of which is expected to be launched in India again by 2012.

Oncology is becoming the research hot-spot:

As indicated above, many domestic Indian pharmaceutical companies are targeting Oncology disease area for developing biosimilar drugs, which is estimated to be the largest segment globally with a value turnover of over US$ 55 billion by the end of this year growing over 17%.

As per recent reports, about 8 million deaths take place all over the world per year due to cancer. May be for this reason the research pipeline of NMEs is dominated by oncology. With the R&D focus of the deep-pocket global pharmaceutical majors’ on this particular therapy area, the trend will continue to go north.

About 50 NMEs for the treatment of cancer are expected to be launched globally by 2015.

Current market size of Oncology drugs in India is estimated to be around Rs.1,300 Crore (US$ 260 million) and is expected to double by 2014.

Greater potential for global collaborative initiatives:

It is envisaged that the recent Pfizer – Biocon deal will trigger many other collaborative initiatives between the global and the local pharmaceutical companies.

Among Indian biotech companies, Reliance Life Sciences has already marketed Recombinant Erythropoietin, Recombinant Granulocyte Colony Stimulating Factor, Recombinant Interferon Alpha and Recombinant tissue plasminogen activator and has been reported to have the richest pipeline of biosimilar drugs in India.

Companies like Wockhardt, Lupin, DRL and Intas Biopharmaceuticals are also in the process of developing an interesting portfolio of biosimilar drugs to fully encash the fast growing global opportunities.

‘Patent Cliff’ is hastening the process:

Many large research-based global pharmaceutical companies, after having encountered the ‘patent cliff’, are now looking at the small molecule generic and large molecule biosimilar businesses, in a mega scale, especially in the emerging markets of the world like India.

The country has witnessed major acquisitions like, Ranbaxy, Shantha Biotechnics and Piramal Healthcare by Daiichi Sankyo of Japan, Sanofi of France and Abbott of USA, respectively. We have also seen collaborative initiatives of large global companies like, GSK, AstraZeneca, and Pfizer with Indian companies like DRL, Aurobindo, Claris, Torrent, Zydus Cadila, Strides Arcolab, Sun Pharma and now Biocon to reach out to the fast growing global generic and biosimilar drugs markets.

This trend further gained momentum when immediately after Biocon deal, Pfizer strengthened its footprints in the global generics market with yet another acquisition of 40% stake in Laboratorio Teuto Brasileiro of Brazil with US$ 240 million to develop and globally commercialize their generic portfolio.

Emergence of ‘second generation’ biosimilar drugs and higher market entry barrier:

Emergence of second generation branded biosimilar products such as PEGylated products Pegasys and PegIntron (peginterferon alpha) and Neulasta (pegfilgrastim), and insulin analogs have the potential to reduce the market size for first generation biosimilar drugs creating significant entry barrier.

The barriers to market entry for biosimilar drugs are, by and large, much higher than any small molecule generic drugs. In various markets within EU, many companies face the challenge of higher development costs for biosimilar drugs due to stringent regulatory requirements and greater lead time for product development.

Navigating through such tough regulatory environment will demand a different type of skill sets from the generic companies not only in areas of clinical trials and pharmacovigilance, but also in manufacturing and marketing. Consequently, the investment needed to take biosimilar drugs from clinical trials to launch in the developed markets will indeed be quite significant.

Government support in India:

To give a fillip to the Biotech Industry in India the National Biotechnology Board was set up by the Government under the Ministry of Science and Technology way back in 1982. The Department of Biotechnology (DBT) came into existence in 1986. The DBT now spends around US$ 200 million annually to develop biotech resources in the country and have been making reasonably good progress.

The DBT together with the Drug Controller General of India (DCGI) has now prepared regulatory guidelines for biosimilar Drugs, which are expected to conform to international quality and patients’ safety standards.

Currently, a number both financial and non-financial incentives have been announced by the Central and the State Governments to encourage growth of the biotech industry in India, which include tax incentives, exemption from VAT and other fees, grants for biotech start-ups, financial assistance with patents, subsidies on investment from land to utilities and infrastructural support with the development of ten biotech parks through ‘Biotechnology Parks Society of India’.

However, many industry experts feel that R&D funding for the Biotech sector in the country is grossly inadequate. Currently, there being only a few ‘Venture Capital’ funds for this sector and ‘Angel Investments’ almost being non-existent, Indian biotech companies are, by and large, dependent on Government funding.

Conclusion:

Recent international deal of Pfizer and Biocon to globally commercialize Biocon’s four biosimilar insulin and analogues developed in India, does signal a new global status for the Indian biosimilar drugs to the international pharma majors, who were vocal critics of such drugs developed in India, until recently.

Biologic Drugs: The hunt for the ‘Magic Bullets’ is on

Posted on December 5, 2011 by Tapan Ray

The global pharmaceutical industry is now navigating its way through very cautiously while negotiating an unprecedented ‘patent cliff’, simultaneously with gradually drying-up R&D pipelines. This unique situation has triggered off several global mega Mergers and Acquisitions (M&A) not only involving better protected biologic drugs business, but also in the large generic space mostly in the emerging markets of the world, which used to be ignored by many before the turn of the new century.

Patent Expiry in next 12 months:

According to an article published in the ‘FiercePharma’ dated October 24, 2011 titled, ‘10 largest U.S patent losses’, over the next 12 months the following best-selling drugs, ranked not by US sales volume but by their weight in each company’s US revenue stream, will face patent expiry:

	Company	Brand
1	Forest Laboratories	Lexapro
2	Takeda Pharmaceuticals	Actos
3	Bristol-Myers Squibb	Plavix
4	AstraZeneca	Seroquel
5	Eli Lilly	Zyprexa
6	Pfizer	Lipitor*
7	Merck	Singulair
8	Novartis	Diovan
9	Teva Pharmaceuticals	Provigil
10	Abbott Laboratories	TriCor

* Patent expired on November 30, 2011

Opening a new vista of opportunity:

In the midst of such a critical situation within the global pharmaceutical industry, application of biotechnology in the drug discovery process opened up a new vista of a broad range of new class of therapies. These include monoclonal antibodies, therapeutic protein hormones, cytokines tissue growth factors, cell or gene therapies and vaccines, just to name a few.

A recent report of the Organization for Economic Cooperation and Development (OECD) predicts that 80% of the total biotech products, which are expected to be commercialized by 2030, will be medicines and medical diagnostics.

Old business model signals a diminishing return:

Over a period of decades, the business model of small-molecule based blockbuster drugs has successfully catapulted the global pharmaceutical business to a high-margin, dynamic and vibrant industry. However, a time has now come when the golden path from the ‘mind to market’ of the drug discovery process is becoming increasingly arduous and prohibitively expensive.

Deploying expensive resources to discover a New Chemical Entity (NCE) with gradually diminishing returns in the milieu of ‘me too’ types of new drugs, does no longer promise a strong commercial incentive.

A shift in focus from ‘small molecules’ to ‘large molecules’:

Since last several years, the success of biologic drugs compared to conventional small-molecule chemical drugs, has been changing the area of focus of pharmaceutical R&D altogether, making the biotech companies interesting targets for M&A.

As per published data, although the market capitalization of the top ten large pharmaceutical companies dropped more than US$ 700 billion since 2001, the same for the biotech companies, on the other hand, has gone up by more than 50% during this period. This trend signifies proliferation of biotech drugs in the years ahead for meeting unmet needs of the patients.

To keep pace with the biotech led growth of the global pharmaceutical industry, many companies have started imbibing biotech-like R&D structure within their respective organizations. For examples, the pharmaceutical majors GsK and Pfizer have already articulated the strategic intent to restructure their respective large monolithic R&D set-ups to smaller independent drug discovery units.

Such restructuring is expected to foster ‘can do’ spirit of the biotech entrepreneurs within the recreated smaller units of large R&D setups to accelerate overall R&D productivity for enrichment of the new product pipelines. However, future will be the best judge to evaluate the success of this experiment.

As if to vindicate this emerging scenario, on November 30, 2011 Bloomberg reported, “U.K.’s largest drug maker has broken up research into competitive teams and put scientists back at the center of the process. But freedom carries a price: researchers who don’t adapt must go. Scientists now ‘live or die with their project.’ This month, Glaxo (GsK) completed the first appraisal of its new model. The company is now deciding which teams deserve more funding and which ones don’t. The conclusions will probably be made public in February when Glaxo (GsK) reports full-year earnings.”

Biologic drugs offer greater promise to meet more unmet needs:

Unlike conventional chemical drugs, most genetically modified biologic drugs work with a very high degree of precision and accuracy on the cells of the diseased organ. Many clinical studies have amply demonstrated that such drugs not only ensure faster recovery, but also help saving incremental treatment cost because of their excellent safety profile.

As we see today, more and more of those global pharmaceutical companies, who used to spend around 15% to 20% of their annual sales for R&D projects are channelizing a large part of the same to effectively compete in the fast evolving market of biologic drugs mainly through M&A. This strategy well justifies their strategic intent to make good the loss of income from the blockbuster drugs going off-patent quite in tandem with their fast dwindling R&D pipeline, as it were.

The bottom-line impact of a successful well targeted new biologic molecule to treat intractable ailments like, various types of cancer and blood disorders, auto-immune and Central Nervous System (CNS) related diseases, neurological disorders such as Parkinson’s, Myasthenia gravis, Multiple Sclerosis and Alzheimer’s disease, are expected to be huge.

Faster growth of biologic drugs:

Despite patent cliff, large molecule biologic drugs like Enbrel, Remicade, Avastin, Rituxan and Humira continue to contribute more than the small molecule drugs of chemical origin to overall growth of the large global pharmaceutical majors. Many of these drugs were sourced by them either through acquisitions or collaborative arrangements.

Cash strapped biotech companies with molecules ready for human clinical trials or with target molecules falling in the well sought after growth areas like, monoclonal antibodies, vaccines, cell or gene therapies, therapeutic protein hormones, cytokines and tissue growth factor are becoming attractive acquisition targets of the small molecules dominated large pharmaceutical companies having deep pockets.

Global Market Scenario:

According to IMS Health, biologics contribute around 17% of global pharmaceutical sales and generated a revenue of US$ 120 billion during MAT March 2009

In 2010 Biologic drugs increased their turnover to US$ 140 billion in the total market of US$ 850 billion. The sale of Biosimilar drugs outside USA exceeded US$ 1 billion.

Six biologic drugs featured in the top 12 and eight in the top 20 best selling global brands. Remicade emerged as the highest-selling biologics in 2010, ahead of Enbrel. Roche remained the top company by sales for biologics with anticancer and monoclonal antibodies. (source: Knol 2010)

Major acquisitions from 2005-2011 for Biologic drugs:

The opportunity of meeting the unmet needs of the patients with effective biologic drugs, especially in high-growth therapy areas, has given the M&A activities in the pharma-biotech space an unprecedented thrust in the recent times.

Following are the major acquisitions in the field of biologic drugs from 2005 to 2011:

Company	Target company	The deal: $billion	Products
Roche	Genentech	47	Rituxan, Avastin, Herceptin, MoAbs, Oncology
Sanofi Aventis	Genzyme	20	Orphan biologicsCerezyme, Fabrazyme, Renagel, Synvisc
AstraZeneca	MedImmune	15.6	Monoclonal Antibodies
Merck	Serono	13.5	Biologics
Takeda	Millennium	8.8	Velcade, Oncology
Lilly	ImClone	6.0	Erbitux, Oncology
Novartis	Chiron	5.8	Vaccines
Teva	Cephalon	6.2	Nuvigil, Provigil, Treanda CNS, Oncology
Abraxis	American BioScience	4.2	Oncology
Astellas	OSI Pharma	4.0	Tarceva, oncology
Eisai	MGI Pharma	3.9	Aloxi, Salagen, Hexalen, Oncology
Celgene	Pharmion	2.9	Oncology
Celgene	Abraxis	2.9	Oncology
Gilead	Myogen	2.5	Biotechnology
BMS	Medarex	2.4	Monoclonal antibodies
J&J	Crucell	2.3	Vaccines
Amgen	Abgenix	2.2	Monoclonal antibodies
Boehringer Ingelheim	MacroGenics	2.1	Monoclonal antibodies
Gilead	CV Terapeutics	1.4	Cardiovascular
Genzyme	Osiris	1.4	Prochymal, Stem cells
GSK	ID Biomed	1.3	Biologics
AstraZeneca	Cambridge Antibody Technology	1.3	Monoclonal Antibodies
Merck	Sirna	1.1	RNAi
Amgen	BioVex	1	OncoVex

(Source: Mergers and Acquisitions Review2005-2011 Pharma Biotech by Knol)

Why do so many companies want to enter into the biotech space?

The answer to the key question of why do so many companies want to enter into the biotech space of the business, in summary, could lie in the following:

Truly innovative small molecule discovery is becoming more and more challenging and expensive with the low hanging fruits already being plucked.
More predictable therapeutic activity of biologics with better safety profile.
A higher percentage of biologic drugs have turned into blockbuster drugs in the recent past.
Market entry barrier for biosimilar drugs, after patent expiry of the original molecule, is much tougher than small molecule generics.
A diverse portfolio of both small and large molecules will reduce future business risks.

A recent study:

In one of their recent collaborative studies published in an article titled, “Is R&D Earning its Investment?” Deloitte and Thomson Reuters (2009) have reported that the top 12 global pharma majors have 21% to 66% biologic drugs in their late stage product pipeline with the average being at 39%.

Another interesting trend:

Besides mega acquisitions, relatively smaller pharmaceutical players have started acquiring venture-backed biotech companies to enrich their product pipelines with early-stage drugs at a much lesser cost. For example, with the acquisition of Calistoga for US $ 600 million and venture-backed Arresto Biosciences and CGI Pharmaceuticals, Gilead known for its HIV drugs, expanded into blood cancer, solid tumor and inflammatory disease segments. In 2009 the same Gilead acquired CV Therapeutics for US $1.4billion to build a portfolio for cardiovascular drugs. In November 2011, Gilead acquired ‘Pharmasset’ for US$ 11 billion to include in its product pipeline a future Hepatitis C drugs offering 95% cure rates.

Smaller biotech companies usually do not get engaged in very large deals unlike the top pharma players, but make quick, decisive and successful smaller deals more effectively.

Much less generic competition for biologic space:

After patent expiry of NCEs, innovators’ brands become extremely vulnerable to cut throat generic competition with as much as 90% price erosion. This happens as the small molecules are relatively easier to replicate by the generic manufacturers. Moreover, the process of getting regulatory approval of NCEs is also not as stringent as biosimilar drugs in most of the markets of the world.

On the other hand biosimilar drugs involving difficult, complex and expensive processes for development with stringent regulatory requirements for getting their marketing approval in the developed markets of the world like the EU and the USA, offer significant brand protection from generic competition for quite some time, even after the patent expiry.

Mainly due to this reason, brands like the following are expected to go strong for some more time without any significant competition from the biosimilar drugs:

Brand	Company	Launch date
Rituxan	Roche/Biogen idec	1997
Herceptin	Roche	1998
Remicade	Centocor/J&J	1998
Enbrel	Amgen/Pfizer	1998

Smaller biotech companies to be the prime targets:

In my view, the voracious appetite of large pharmaceutical companies for inorganic growth through mega M&A, will ultimately subside due to various compelling reasons. Instead, smaller biotech companies, especially with products in Phase I or II of clinical trials, without wherewithal to take them to subsequent stages of development, will be the prime targets for acquisition by the pharma majors at an attractive valuation.

Cost of treatment:

Despite so many positives, high priced biologic drugs do raise a critical concern about the incremental load on already ballooning healthcare costs to the patients.

The Wall Street Journal (WSJ) in its September 29, 2010 issue highlighted that biologic drugs can cost as much as $1.5 million annually to the user. Similarly Forbes.com on April 12, 2009 reported, “Biologic drugs can cost up to 22 times more than traditional medications – some as much as $400,000 a year”.

This is indeed a very serious issue that needs to be resolved sooner. Speedy entry of biosimilar drugs will partly address this critical issue.

Conclusion:

Although the large pharma majors have already started experimenting to work with the pure biotech companies in terms of M&A and strategic alliances, it will be interesting to watch the long term ‘DNA Compatibility’ of the business models, organization/ work/employee culture and market outlook of these two different types of organizations while improving the global business performance of the overall entity, significantly.

Only future will tell us whether or not just restructuring of the R&D set up of companies like, Pfizer, Merck, Roche and perhaps Sanofi at a later date, helps synergizing the overall R&D productivity of the merged entities.

Be that as it may, despite serious cost concern, experts still believe that biologic drugs have all the potential to deliver the ‘magic bullets’ in the fight against many intractable diseases of mankind in not too distant future.

Hence the hunt is on.

Biosimilar Drugs: The Roadblocks and the Road Ahead

Posted on September 5, 2011 by Tapan Ray

Unlike commonly used ‘small molecule’ chemical based drugs, ‘large molecule’ biologic drugs are developed from living cells and using very complex processes. These groups of drugs could range from simpler insulin to therapy for treating complex ailments like, cancer and almost invariably attract a high price tag, which could run even in thousands of dollars.

It is virtually impossible to replicate these protein substances, unlike the ‘small molecule’ drugs. One can at best develop a biologically similar molecule with the application of high degree of biotechnological expertise. These drugs are usually much less expensive than the original ones and called ‘Biosimilar Drugs’. It is expected that ‘biosimilar drugs’ will have lesser market competition than the conventional ‘small molecule’ generic drugs, mainly because of complexity and costs involved in their developmental process.

Future growth potential:

In most of the developed countries, besides regulatory issues, ‘Biosimilar drugs’ are considered to be a threat to the fast growing global biotech industry. At the same time, it is widely believed that in the rapidly evolving global concern for cheaper and more affordable medicines for patients across the world, relatively smaller biotech companies, given the required wherewithal at their disposal, could emerge as winners in this new ball game as compared to traditional generic pharmaceutical players.

Novartis (Sandoz) – first to launch a ‘Biosimilar drug’ in the US:

In mid-2006, US FDA approved its first ‘Biosimilar drug’- Omnitrope of Sandoz (Novartis) following a court directive. Omnitrope is a copycat version of Pfizer’s human growth hormone, Genotropin. Interestingly, Sandoz had also taken the US FDA to court for keeping its regulatory approval pending for some time in the absence of a well-defined regulatory pathway for ‘Biosimilar drugs’ in the USA. The CEO of Sandoz had then commented, “The FDA’s approval is a breakthrough in our goal of making high-quality and cost-effective follow-on biotechnology medicines like Omnitrope available for healthcare providers and patients worldwide”. Despite this event, none at that time expected the US FDA to put regulatory guidelines in place for approval of ‘Biosimilar drugs’ in the country.

Merck’s entry was through an acquisition:

Merck announced its entry into the ‘Biosimilar drugs’ business on February 12, 2009 with its acquisition of Insmed’s portfolio for US$ 130 million in cash. Rich pipeline of follow-on biologics of Insmed is expected to help Merck to hasten its entry into global ‘Biosimilar drugs’ markets.

Other recent global initiatives:

Merck paid US$ 720 million to Hanwha for rights to its copy of Enbrel of Amgen
Samsung of South Korea has set up a biosimilars joint venture with Quintiles to create a contract manufacturer for biotech drugs.
Celltrion and LG Life Sciences have expressed global ambitions in biosimilar drugs.
Dr Reddy’s Laboratories (DRL) has already been marketing a biosimilar version of Rituxan of Roche since 2007.
According to Reuter (June 22, 2011), Merck, Novartis (Sandoz), Teva and Pfizer are expected to be strong players in the biosimilar market.
Reliance Life Science though has faced a setback in Europe with the regulators asking for more data for its copy of EPO prompting them to withdraw their application for now, is also a potential player in the biosimilar market.

Many other developments are also now taking place in the space of ‘Biosimilar drugs’, the world over. To fetch maximum benefits out of this emerging opportunity, India has started taking steps to tighten its regulatory process for marketing approval of such drugs. This is absolutely necessary to allay general apprehensions on drug safety with inadequate clinical data for similar protein substances.

Current status in the US:

President Barak Obama administration of the US has been expressing for quite some time a strong intent to pave the way for ‘Biosimilar drugs’ in the US. To facilitate this process, a new draft legislation titled, “Promoting Innovation and Access to Life Saving Medicine Act” was introduced by the legislators of the country. This legislation came into force with the announcement by US-FDA the outline of how biopharmaceutical players can submit their application for marketing approval of ‘Biosimilar drugs’ in the country. Many industry players have since then been gearing up, across the world, to have a share of the potentially large ‘biosimilar drugs’ market in the US.

Challenging clinical data requirements in the US:

According to ‘Biologics Price Competition and Innovation Act of 2009 (BPCI Act)’, which was enacted in the US on March 23, 2010, any biological substance to be “biosimilar” will require to be “highly similar to the reference product, notwithstanding minor differences in clinically inactive components”. BPCI also specifies that there should be “no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product”. It is interesting to note that the Act emphasizes on ‘clinical similarity’ rather than ‘biological or structural similarity’ between the original and ‘biosimilar drugs’.

The New England Journal of Medicine dated August 4, 2011 reported that US-FDA is in the process of establishing very challenging clinical requirements from the makers of ‘biosimilar drugs’ for obtaining marketing approval in the country. Such stringent regulatory requirements are expected to push up the cost of development of ‘biosimilar drugs’ significantly, seriously limiting the number of players in the market.

12 years Exclusivity in the US:

In the US, the innovator companies get 12 years exclusivity for their original biologic drugs from the date of respective marketing approvals by the FDA.

The BPCI Act clearly specifies that applications for ‘biosimilar drugs’ to the FDA will not be made effective by the regulator before 12 years from the date of approval of the innovators’ products. In addition, if the original product is for pediatric indications, the 12-years exclusivity may get an extension for another six months.

However, the key point to note here is, if the FDA starts its review process for the ‘biosimilar drugs’ only after the 12 year period, the innovator companies in that case, will effectively get, at least, one more year of exclusivity over and above the 12 years period, when the applicants for ‘biosimilar drugs’ will keep waiting for marketing approval from the FDA.

The market:

According to Datamonitor the global market for ‘biosimilars drugs’ is expected to grow from US$ 243 million in 2010 to around US $3.7 billion by 2015.

Another report points out that only in the top two largest pharmaceutical markets of the world, the USA and EU, sales of ‘biosimilar drugs’ will record a turnover of US$ 16 billion in the next couple of years when about 60 biotech products will go off-patent.

The Indian biotech players:

Such a lucrative business opportunity in the west is obviously attracting many Indian players, like, Biocon, Dr. Reddy’s Labs, Ranbaxy, Wockhardt, Shantha Biotech, Reliance Life Science etc., who have already acquired expertise in the development of ‘Biosimilar drugs’ like, erythropoietin, insulin, monoclonal antibodies, interferon-Alfa, which are not only being marketed in India but are also exported to other non/less-regulated markets of the world.

Ranbaxy in collaboration with Zenotech Laboratories is engaged in global development of Granulocyte Colony-Stimulating Factor (GCSF) formulations. Wockhardt is expected to enter into the Global ‘Biosimilar drugs’ market shortly. Dr. Reddy’s Laboratories and Biocon are also preparing themselves for global development and marketing of insulin products, GCSF and streptokinase formulations.

Funding by the Government of India:

It has been reported that the Department of Biotechnology (DBT) of the Government of India has proposed funding of US$ 68 million for ‘biosimilar drugs’ through Public Private Partnership (PPP) initiatives, where soft loans will be made available to the Indian biotech companies for the same. Currently DBT spends reportedly around US$200 million annually towards biotechnology related initiatives.

Key success factors for rapid acceptance in the developed markets:

According to a new research finding from ‘The Decision Resources’, one of the key success factors for any such new drugs is how quickly the specialists will accept them. So far as biosimilar drugs are concerned they noted a high level of concern, if such drugs are not supported by robust sets of clinical data on the claimed treatment indications.

Conclusion:

With increasing global cost-containment pressures within the healthcare space, the emergence of a lucrative global ‘biosimilar drugs’ market now appears to be inevitable.

In the fast evolving scenario, major research based global bio-pharma and even the pure pharmaceutical companies will have two clear choices. The first choice is the conventional one of competing with ‘biosimilar drugs’ in all important markets of the world. However, the second choice of jumping into the fray, keeping undiluted focus on R&D, appears to be more prudent and perhaps will also make a shrewd horse sense. Only future will tell us, which of these two business senses will prevail, in the run up to success, for the global biotech companies.

With the above background, the report from the ‘Business Wire’ highlighting the fact, ‘the manufacture and development of a biosimilar molecule requires an investment of about US$ 10 to 20 million in India, as compared to US$ 50 to 100 million in developed countries’, vindicates the emergence of another lucrative business opportunity for India.

With around 40% cost arbitrage, as indicated above and without compromising on the required stringent international regulatory standards, the domestic ‘biosimilar’ players should be able to establish India as one of the most preferred manufacturing destinations to meet the global requirements for ‘biosimilar drugs’.

In addition to cost efficiency, available skill sets in developing ‘biosimilar drugs’, will offer another critical advantage to the domestic players in reaching out to the international ‘biosimilar drugs’ markets either by themselves or with appropriate collaborative arrangements, just as we have recently witnessed in case of Biocon’s strategic collaboration with Pfizer in this rapidly evolving sector of the world.

Disclaimer:The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Patients’ Safety, regulatory approval of Biosimilar Drugs in India and WHO Biosimilar guidelines

Posted on August 9, 2010 by Tapan Ray

Biopharmaceutical drugs are broadly defined as:

”Those medicines produced using a living system or genetically modified organism. These drugs are different from traditional chemical medicines in many ways. Size of the molecule is one of the most obvious distinctions: the molecules of a biopharmaceutical medicine are much larger, have far more complex spatial structures and are much more diverse (“heterogeneous”) than the chemical molecules which make up classical drugs.”

The Biosimilar drugs:

Biosimilar drugs are follow-on versions of original biopharmaceutical medicines. Biosimilar medicines are intended to have the same mechanism of action for the same diseases as the original biopharmaceutical drugs.

The term “bio generic” will be misleading for off patent biopharmaceutical products, as no two biopharmaceutical products could possibly be exactly identical. This is mainly because of the following reason:

“Whereas generics of chemistry based medicines are identical in the molecular structure and therefore copies of the original product, based on a strict definition of “sameness”, a corresponding definition cannot be established for biosimilar medicines because of their nature and the complexity of their manufacturing process. Here post-translational modifications are dependent of the host cell and the process.”

Thus the common terminologies used to describe such products when the original products go off-patent are follow-on biologics and biosimilars.

Manufacturing Conditions of biosimilars ultimately define the final product:

Unlike chemical drugs, the manufacturing conditions and the process followed to produce biopharmaceutical drugs largely define the final product and its quality. Any alteration to the manufacturing process may result in a completely different product. Additionally proteins are relatively unstable. Thus additional measures in their storage, formulation and delivery are very critical.

Key concerns with the existing regulatory approval process for Biosimilar drugs:

• Small changes in the manufacturing process of biosimilar drugs could significantly affect the safety and efficacy of the molecule.

• Due to the very nature of a biologic it is virtually impossible for two different manufacturers to manufacture two identical biopharmaceutical drugs. Identical host expression systems, processes and equivalent technologies need to be demonstrated in extensive comparability trials. Thus, as stated above, a ‘bio generic’ cannot exist.

• As against the situation applicable for generics of chemical molecules which can be replicated, biosimilar drugs cannot be replicated. At the most such biopharmaceuticals can be at the most “similar” but not “identical” to the original reference products. To ensure desired efficacy and safety of biosimilar products, these products should only be approved after charting out a formal and well validated regulatory pathway for the biosimilar drugs in India.

• Currently biosimilar drugs are given marketing approval by the regulator without such guidelines for large molecule biological and following just the bioequivalence model as specified in the Schedule Y of the Drugs and Cosmetics Act (D&CA) of India for small molecule chemical entities only, as the current Drugs and cosmetics Acts of India, very unfortunately, do not differentiate between large and small molecular drugs. This could, in turn, endanger patients’ safety with serious medical consequences.

Although, Central Drugs Standard Control Organization (CDSCO) and the Drugs Controller General of India (DCGI) are responsible for approvals of the new drug applications, health being a state subject, respective state regulatory authorities are responsible for granting manufacturing license to the pharmaceutical manufacturers.

Pharmaceutical manufacturers setting up facilities in the states, where regulatory oversight and incidences of weaker enforcement are common, will be able to market their products, including biosimilars, across the country. It is alleged that there are hardly any regulatory control over the mistakes or offences committed by the State Drug authorities who permit manufacture of drugs even unapproved by the DCGI. The existing issue of mushrooming of various irrational Fixed Dose Combinations (FDC) products in India will vindicate this point.

The Government’s response to this public health concern:

Express Pharma in its June 30, 2009 edition reported Dr M K Bhan, Secretary, Government of India, DBT, saying, “The first question is do we have written guidelines available to people? Currently, we have a large committee of about 30 people in the Review Committee on Genetic Manipulation (RCGM) which frequently discusses the current FDA and EMEA guidelines and makes sure that it is updated as per the guidelines in case by case approvals.”

He acknowledged, to make sure that the product is identical or original is harder for biological than for chemical entities and said, “So the next question is, what is the degree of difficulty you create to be sure that some of the products in the in vitro laboratories and the strength of the biomolecule, are to be characterized in details, and the other side is how expensive should the chemical evaluation be? At this moment, RCGM is seeing the issues and is in touch with both the FDA and the EMEA, and they are taking case by case decisions while trying to standardize the minimum information that is required to show how companies have characterized their products.”

“If we ask a big established company on this issue they will tell us to be strict, whereas a smaller company will suggest otherwise. What we are trying to do is being very scientific and come to a conclusion,” reported Express Pharma quoting Dr. Bhan.

The current practice:

Much water has flown down the bridge since the above interview was published. Nothing much has changed on ground regarding this critical issue, thus far. The industry sources allege that even today regulatory approval of biosimilar drugs (large molecules) are granted based on Phase III clinical trials, as specified in the schedule Y of the Drugs and Cosmetics Acts for the small molecules (chemicals) and that too conducted mostly on just 40 to 45 patients. At times the number of patients studied is even lesser. Immunogenicity study, which is so important for biosimilar drugs is, more often than not, overlooked. This could seriously compromise patients’ safety with such category of drugs.

Conclusion:

It is, indeed, quite surprising that in our country there is still no separate transparent and published guidelines for regulatory approval of Biosimilar drugs even when the World Health Organization (WHO) has come out with the same and India had actively participated in that exercise.
The question, therefore, comes to my mind whether the Biosimilar drugs manufactured in India would conform to international quality and safety standards, like in the U.K or what has been recently announced in the USA? If not, who will address the safety concerns of the patients administering these life saving medicines?

Such a concern gets vindicated by widely reported serious quality problems, detected by the drugs regulatory authorities, at some large and well known Biosimilar drug’s manufacturing units in India, in not too distant past and also from the condition of some vaccine manufacturing units in our country. The recent example of WHO cancelling the pre-qualification of ‘Shan 5’ (Shanta Biotech) vaccines for quality related problems, perhaps may help opening the eyes of our regulators, on the related patients’ safety issues arising out of regulatory laxity.

This issue assumes even greater importance considering the very recent development of the Department of Biotechnology (DBT) unfolding an interesting scheme to encourage development of biosimialr dugs in India by offering financial support to the domestic pharmaceutical and biopharmaceutical industry.

The proposed new regulatory pathway for the marketing approval of Biosimilar drugs in India will immensely help paving the way for the Biopharmaceuticals drugs manufacturers in India to adequately prepare themselves to grab a significant share of the fast emerging Biosimilar drugs markets, particularly, in Europe and the USA, in the years to come.

The Ministry of Health and the Department of Biotechnology of the Government of India should, therefore, urgently and jointly consider amending the Drugs & Cosmetics Acts of India accordingly and establish robust regulatory guidelines for marketing approval of biosimilar drugs in the country, acknowledging the widespread concern for patients’ safety.

By Tapan Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

With significant competitive edge should Global Biotech Companies consider entry into high potential ‘Biosimilar drugs’ business?

Posted on May 7, 2009 by Tapan Ray

‘Biosimilar drugs’ – rapid future growth potential:

In most of the developed countries of the world, besides regulatory issues, ‘Biosimilar drugs’are considered a threat to the fast growing global biotech industry. However, many believe that innovative biotech companies can have a head start with all wherewithals at their disposal, compared to generic pharmaceutical companies, to convert this seemingly significant threat into a bright emerging opportunity and derive the best possible mileage out of such changing environment.

Sandoz (Novartis) – first to launch a ‘Biosimilar drug’ in the USA:

In mid 2006, US FDA approved its first ‘Biosimilar drug’; Omnitrope of Sandoz (Novartis) following a court directive in the U.S. Omnitrope is a copycat version of Pfizer’s human growth hormone, Genotropin. Interestingly, Sandoz (Novartis) had taken the U.S FDA to court as the regulatory approval of Omnitrope was kept pending by them, in absence of a defined regulatory pathway for ‘Biosimilar drugs’ in USA.

The CEO of Sandoz had then commented, “The FDA’s approval is a breakthrough in our goal of making high-quality and cost-effective follow-on biotechnology medicines like Omnitrope available for healthcare providers and patients worldwide.” Despite this event, no one at that time expected the U.S FDA to start commencing approval of other ‘Biosimilar drugs’ within the country.

‘Biosimilar drugs’ – emerging global interest:

Thereafter, many developments are fast taking place in the space of ‘Biosimilar drugs’, the world over. To fetch maximum benefits out of this emerging opportunity, India is also taking steps to tighten its regulatory reform process for ‘Biosimilar drugs’ to allay general fear and apprehensions regarding safety of such drugs, in absence of adequate clinical data for the specific protein substance.

Merck’s entry in ‘Biosimilar drugs’ business is through an acquisition:

In the west Merck announced its entry into the ‘Biosimilar drugs’ business on February 12, 2009, while announcing its acquisition of Insmed’s portfolio of ‘Biosimilar drugs’ for U.S$130 million in cash. Rich pipeline of follow-on biologics of Insmed is expected to help Merck to hasten its entry into global ‘Biosimilar drugs’ markets.

Current status of ‘Biosimilar drugs’ in the USA:

The new administration of President Barak Obama has expressed its strong intent to pave the way for regulatory guidelines for ‘Biosimilar drugs’ in the USA. To facilitate this process, the new draft legislation titled, “Promoting Innovation and Access to Life Saving Medicine Act” has already been introduced by the legislators of the country. This legislation, when will come into force would help define guidelines for approval of ‘Biosimilar drugs’ in the USA with just a five year exclusivity period to the innovative products, against a demand of 14 years by the global biotechnology industry.

Lucrative Global market potential for ‘Biosimilar drugs’:

It is estimated that only in the top two largest pharmaceutical markets of the world, USA and EU, sales of ‘Biosimilar drugs’ will record a turnover of U.S$ 16 billion in next two years and around U.S$ 60 billion by year 2010, when about 60 biotech products will go off-patent.

Opportunity for the Indian biotech companies:

Such a lucrative business opportunity in the west will obviously attract many Indian players, like, Biocon, Dr. Reddy’s Labs, Ranbaxy, Wockhardt etc, who have already acquired expertise in the development of ‘Biosimilar drugs’ in India like, erythropoietin, insulin, monoclonal antibodies, interferon-alfa. Domestic Indian biotech players are not only marketing these products in India but also exporting them to other non/less-regulated markets of the world.

Indian Companies are fast preparing to take a sizable share of the global pie of ‘Biosimilar drugs’ market:

Ranbaxy in collaboration with Zenotech Laboratories is engaged in global development of Granulocyte Colony-Stimulating Factor (GCSF) formulations. Wockhards is expected to enter into the Global ‘Biosimilar drugs’ market by 2010. Dr. Reddy’s Laboratories and Biocon are also preparing themselves for global development and marketing of insulin products, GCSF and streptokinase formulations.

Government of India funding for development of ‘Biosimilar drugs’ in India:

It has been reported that the Department of Biotechnology (DBT) of the Government of India has a proposal for funding of U.S$ 68 million through public private partnership (PPP) initiatives, where soft loans at the rate of interest of just 2% will be made available to the Indian biotech companies for development of ‘Biosimilar drugs’. Currently DBT spends around U.S$200 million annually towards biotechnology related initiatives.

Advantage India:

Experience in conforming to stringent U.S FDA manufacturing standards, having largest number of U.S FDA approved plant outside USA; India has acquired a great advantage in manufacturing similar high technology products in India. Significant improvement in conformance to Good Clinical Practices (GCP) standards in India offers additional advantages.

Two available choices for the innovator companies:

With increasing global cost-containment pressures within the healthcare space, emergence of a lucrative global ‘Biosimilar drugs’ market with appropriate defined regulatory pathway in place is inevitable now.

Major global research based companies will now have two clear choices in the fast evolving situation. The first choice is the conventional one of competing with the ‘Biosimilar drugs’ in all important markets of the world. However, the second choice of jumping into the fray of ‘Biosimilar drugs’ business keeping focus on R&D undiluted, appears to be more prudent to me and perhaps will also make a better business sense. Only future will tell us, which of these two business senses will prevail, in the long run for the global biotech companies.

By Tapan Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

PILMAN

A Tapan Ray Website

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