Tag Archives: breast

Herceptin Biosimilar Expands Drug Access to Breast Cancer Patients in India

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Come February 2014, much to the relief of more than 145,000 patients diagnosed with breast cancer in India, Herceptin of Roche, a critical drug for the treatment of the dreaded disease, will face competition, for the first time, from a less expensive biosimilar equivalent. The product named Canmab developed together with Mylan by Biocon has been priced 25 percent less than Herceptin.

Patient access issue for newer cancer therapy:

Herceptin has been a very critical drug, though equally expensive, for breast cancer patients globally.

Mainly because of its unusual high price, the product created an access barrier to majority of patients in India. Arising out of complexity of the problem faced by the cancer patients, hugely compounded by the affordability issue, on January 12, 2013, it was first reported that in a move that is intended to benefit thousands of cancer patients, Indian Government has started the process of issuing Compulsory Licenses (CL) for three commonly used anti-cancer drugs: 

-       Trastuzumab (or Herceptin, used for breast cancer),

-       Ixabepilone (used for chemotherapy)

-       Dasatinib (used to treat leukemia).

For a month’s treatment drugs like, Trastuzumab, 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.

Pricing issue needs a systemic resolution: 

While there is no single or only right way to arrive at the price of a patent protected medicine, how much the pharmaceutical manufacturers will charge for such drugs still remains an important, yet complex and difficult issue to resolve, both locally and globally. Even in the developed nations, where an appropriate healthcare infrastructure is already in place, this issue comes up too often mainly during price negotiation for reimbursed drugs. 

A paper titled, “Pharmaceutical Price Controls in OECD Countries”, published by the U.S. Department of Commerce, after examining the drug price regulatory systems of 11 OECD countries, concluded that all of them enforce some form of price control to limit spending on pharmaceuticals. The report also indicated that the reimbursement prices in these countries are often treated as de facto market price.

Though there is no such system currently prevailing in India, the Government is mulling to put in place a similar mechanism for patented medicines, as captured in the National Pharmaceutical Pricing Policy (NPPP) 2012.

Further, some OECD governments regularly cut prices of even those drugs, which are already in the market. The value of health outcomes and pharmacoeconomics analysis is gaining increasing importance for drug price negotiations/control by the healthcare regulators even in various developed markets of the world to ensure responsible pricing of IPR protected medicines. For various reasons, no such process is followed either for such product pricing in India, as on date.

Roche changed Herceptin strategy for India:

To effectively address the challenge of pricing of patented medicines in India, Roche reportedly entered into a ‘never-before’ technology transfer and manufacturing contract for biologics with a local Indian company – Emcure Pharma for its two widely acclaimed ‘Monoclonal Antibodies’ anti-cancer drugs – Herceptin and MabThera.

Consequently, Roche introduced its ‘made in India’ brand Herclon (Herceptin) with a much-reduced maximum retail price of about Rs. 75,000 for a 440 mg vial and started co-marketing the product with Emcure Pharma in India.

Although Herceptin patent remains valid in the United States (US) until 2018, Roche decided to discontinue its patent rights for Herceptin in India in 2013.

The pharma major reportedly lost this patent earlier in Europe. This vindicates the views of many experts that Herceptin patent was weak, as it would probably not be able to clear the litmus test of a stringent scrutiny under the Patent Acts of India. The report, therefore, argues that core reason for withdrawal of Herceptin patent in India by Roche cannot be attributed, even remotely, to the ‘weak IP ecosystem’ in India.

Biocon Pricing:

According to reports Biocon’s Canmab, the biosimilar version of Herceptin, will be available in 440 mg vial with a maximum retail price of Rs. 57,500 and also in 150 mg vial at Rs. 19,500.

Lower price would lead to greater patient access – Roche argued earlier:

It was reported, when Roche switched over to Herclon with around 30 percent discounted price from very high price Herceptin, access to the drug improved. In fact, that was the logic cited by Roche for the launch of Herclon in India at that time. 

Just to recapitulate, media reports indicated at that time that Roche intends to offer to Indian patients significantly cheaper, local branded version of Herceptin sooner. The same news item also quoted Roche spokesperson from Basel, Switzerland commenting as follows:

“The scope is to enable access for a large majority of patients who currently pay out of pocket as well as to partner with the government to enable increased access to our products for people in need”.

Conclusion:

It is beyond doubt that even with significantly lower price, Canmab would not be able to guarantee 100 percent access to the drug for all breast cancer patients in the country.

However, applying the same logic of Roche, as mentioned above, with further 25 percent price discount for Canmab by Biocon, the access to this drug should expand significantly for over 145,000 diagnosed breast cancer patients in India even, for an argument’s sake, all other factors, including inadequate number diagnostic facilities etc. remain the same. Isn’t that better?

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

 

Pharma Horizon: Cloud, Rainbow And Smear

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Some recent papers contemplated that the patent cliff for blockbuster drugs has already reached the zenith and early signs of recovery should be visible from 2013 onwards. However, from analysis of the currently available data, contrary to the above belief, I reckon, the downtrend in global pharma is far from over, not just yet.

One of the telltale signs of this slump is near-term patent expiry of today’s blockbuster drugs, the impact of which will continue to keep the global pharma sky overcast with clouds for some more time, especially in absence of replaceable equivalents. Interestingly, on the flip side, a beautiful rainbow, as it were, also takes shape in the horizon, ushering-in a hope to a large number of patients for improved access to newer drugs, just as it does to the generic players for accelerating business growth.

That’s the good part of it, though for the generic drug industry. However, the bad part of the emerging scenario gives rise to a lurking fear of gloom and doom, emanating from self-created evitable smears and taints, blended in vessels of despicable mindsets.

Clouds:

While having a glimpse at that following table, the underlying impact of the dark clouds looming large on the global pharma horizon cannot just be wished away:

Total Patent Expiry:

Year Value US$ Billion
2015 66
2014 34
2013 28
2012 55
Total 183 

(Compiled from FiercePharma data)

Thus, the negative impact from sales lost to patent expiry of blockbuster drugs of today, though declined from US$ 55 billion in 2012 to US$ 28 billion in 2013, the same would start climbing-up again to US$ 66 billion in 2015.

If we take a look at the product-wise details, the picture pans out as under:

Top 10 ‘Patent Expiry’ in 2014:

No. Brand Company Disease Sales 2012   US$ Million Expiry
1. Copaxone Teva MultipleSclerosis 3996 May 2014
2. Nexium AstraZeneca Acid peptic 3994 May 2014
3. Micardis/HCT BoehringerIngelheim Hypertension 2217 Jan 2014
4. Sandostatin LAR Novartis Cancer 1512 June 2014
5. Exforge/HCT Novartis Hypertension 1352 Oct 2014
6. Nasonex Merck Resp. Allergy 1268 Jan 2014
7. Trilipix Abbvie Anti-lipid 1098 Jan 2014
8. Evista Eli Lilly Osteoporosis 1010 Mar 2014
9. Renagel Sanofi Chronic Kidney Disease  861 Sep. 2014
10. Restasis Allergan Chronic Dry Eye  792 May 2014

(Compiled from FiercePharma data)

The above figures, therefore, do reinforce the hypothesis that the following factors would continue to make the best brains of global pharma burning the midnight oil in search of sustainable strategic blueprints, at least, for some more time:

-       Mostly, high growth emerging markets of the world are generic drugs driven

-       Increasing cost containment pressure of Governments and/or other payor

-       Challenges from Intellectual Property (IP) and Market Access related  issues

-       Declining R&D productivity

-       Shift in overall focus for new drugs on expensive biologics

-       Markets turning more Volatile, Uncertain, Complex and Ambiguous (VUCA)

Current strategy to deliver shareholder-value not sustainable:

Since last several years, one has witnessed, despite slowing down of sales growth, big pharma players, by and large, have not failed in delivering impressive shareholder returns. This has been possible mainly due to ruthless cost cutting across the board, restructuring of operational framework and taking measures like, increase in dividends and share repurchases.

These strategic measures, though laudable to keep the head above water, are just not sustainable over a period of time sans strong cashflow.

Thus, for a long haul, robust and consistent business growth with commensurate impact on the bottom-line generating smooth cashflow, is imperative for all these companies.

In this difficult ball game of developing sustainable cutting-edge strategies at an equally challenging time, the consolidation process within the industry would gain further momentum, where only the fittest corporations, led by great corporate brains, would manage to survive and thrive.

However, who all would successfully be able to squarely face the moments of truth, triumphantly seizing the opportunities frozen in time, in the fast changing paradigm of a seemingly VUCA world, is not more than a matter of speculation now.

The Rainbow:

As stated above, while this canopy formed with dark clouds keeps looming large at the global pharma horizon, a beautiful rainbow is simultaneously seen taking shape for the domestic Indian drug manufacturers to cash-on with well-orchestrated strategic measures. One of the critical success requirements for this sprint, is touching the tape in the finishing line to become first to introduce generic versions of the patent expired drugs, especially in the US market.

Indian pharma players have already demonstrated in the past that they do have the wherewithal of making such rare opportunities meaningful by offering affordable new drugs of high quality standards to a large number of patients, while simultaneously accelerating growth of their respective business operations.

Proven acumen even in biologics:

India has recently proven its acumen in the area of biologics too, by developing a biosimilar version of the complex biologic drug – Trastuzumab (Herceptin) of Roche, used for the treatment of breast cancer, and that too in a record time.

As is known to many, earlier in 2013 Roche decided not to defend its patents on Herceptin in India, which reportedly recorded local sales of about US$ 21 million in 2012. Many people opined at that time, it would not be easy for any company to develop biosimilar version of Trastuzumab, mainly due to the complexity involved in its clinical development. Hence, some diehards kept arguing, Roche would not be commercially impacted much for taking the above decision, at least in the near to mid term.

Surprising almost everybody, Biocon and its MNC partner Mylan not only developed an affordable biosimilar version of Trastuzumab successfully, but also got its marketing approval from the Drug Controller General of India (DCGI), thereby immensely benefitting a large number of breast cancer patients in India and hopefully even beyond.

Keeping ‘Eye on the ball’?

Details of ANDA status from the USFDA source probably indicate that several Indian players have started gearing up to move in that direction at a brisk pace, keeping their eyes well fixed on the ball.

The following table further indicates that in 2012 India ranked second, after the United States (US) in terms of number of ANDA approvals and in 2013 till October India ranks number one, overtaking the United States (US):

ANDA’s Granted in 2012 and upto October 2013):

Country ANDA 2012 ANDA (October 2013) Total Since 2007
United States 183 119 1191
India 196 138 993
Switzerland 20 12 134
Israel 28 13 133
Canada 27 13 116
Germany 20 6 107
UK 11 15 95
China 7 10 29

Smears:

Unfortunately, just out side the frame of the above kaleidoscope, one can see large spots of self created slimy smears, which can make the ‘Rainbow’ irrelevant, maintaining the horizon as cloudy even for the Indian generic players.

Continuous reports from US-FDA and UK-MHRA on fraudulent regulatory acts, lying and falsification of drug quality data by some otherwise quite capable Indian players, have just not invited disgrace for the country in this area, but also reportedly prompted regulators from other nations trying to assess whether such bans might suggest issues for drugs manufactured for their respective countries, as well.

Such despicable mindsets of the concerned key players, if remain unleashed, could make Indian Pharma gravitating down, stampeding all hopes of harvesting the incoming opportunities. 

We have one such ready example before us and that too is not an old one. The ‘Import Alert’ of the USFDA against Mohali plant of Ranbaxy, has already caused inordinate delay in the introduction of a cheaper generic version of Diovan, the blockbuster antihypertensive drug of Novartis AG, after it went off patent. It is worth noting that Ranbaxy had the exclusive right to sell a generic version of Diovan from September 21, 2012.

Another report of November 2013 states, “The Drug Controller General of India has ordered Sun Pharmaceutical, the country’s largest drug maker by market capitalization to suspend clinical research activities at its Mumbai based bio-analytical laboratory, a move that could slow down the company’s regulatory filings in India and possibly overseas as well.”

The outcome of such malpractices may go beyond the drug regulatory areas, affecting even the valuations of concerned Indian pharma companies. According to a recent report Strides Arcolab will not get US$ 250 million of the US$ 1.75 billion anticipated from the sale of its injectable drugs unit to Mylan Inc unless regulatory concerns at Agila Specialities in Bangalore are resolved.

Thus the smears though for now are confined to a few large manufacturing units of Indian Pharma, including some located overseas, may eventually play the spoil sport, trashing all hopes seen through the rainbow in the bins of shame.

Conclusion:

In the balance of probability, I believe, the clouds of uncertainty would continue to loom large over the global pharma, at least, till 2015.

However, in the midst of it, heralds a ‘never before opportunity’ for Indian pharma to cash on the early fruits of forthcoming patent expiries of today’s blockbuster drugs, not just for them, but for patients at large.

Already demonstrated capabilities of the homegrown players, trigger expectations of making it happen. The encouraging trend of grant of ANDAs in the US further reinforces this belief.

Despite all these, a lurking fear does creep in. This evitable fear finds its root in repeated fraudulent behavior of some Indian drug manufacturers, seriously compromising with cGMP standards of global drug regulators, including lying and falsification of data generated, thus playing a spoil sport by ‘snatching defeat from the jaws of victory’, as it were.

That said, the question to ponder now is: In the ‘Pharma Horizon’ what would ultimately prevail in the short to medium term, especially in the Indian context – Clouds, The Rainbow or Smears?

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.

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

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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.

An El Dorado…But Not Without Responsible Pricing:The Cancer Segment in India

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The affordability issue for cancer treatment has been the subject of a raging debate since quite some time, as the incidence of cancer is fast increasing across the world. Just for example a very recent report highlighted that cancer has now become the greatest health risk in the UK, with an average British boy born in 2010 running a 44 percent chance of being diagnosed with any form of cancer during his lifetime. The risk for a baby girl is slightly lower at 40 percent.

In India too, the problem of affordable cancer treatment has now become the center piece of a fiercer public opinion in the healthcare space, more than even HIV, prompting the Government to intervene in this dreadful disease area and address the problem in a holistic way both in the short and also on a longer term basis. This demand is supported by rapidly growing number of cancer patients in the country.

Out of the total number of new cancer patients globally, India now reportedly ranks third as follows:

Rank Country % Of total
1. China 22
2. USA 11
3. India 7.5

As a consequence, cancer now reportedly accounts for one of the main causes of deaths  in India, which is nearly 19 percent higher than deaths caused by heart diseases.

Number of new cancer patients staggering in India:

Over 60,000 new cases are reportedly diagnosed every year in India and 80 percent of them are at an advanced stage, which involve mostly the middle-aged and elderly population of the country, where affordability is even a greater issue.

Cervical and breast cancers are reportedly the most common, contributing over 26 per cent to the total cancer cases in India, followed by lung, mouth, pharynx, ovarian, pancreatic and esophagus cancers.

Whereas cervical cancer is reportedly most common in females with a mortality rate of nearly 15 per 10,000 females, lung cancer has the highest mortality rate of 28 per 10,000 males.

Incidentally, lung cancer is the most commonly diagnosed cancer even globally. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 90% of all lung cancers. The primary cause of lung cancer in up to 90% of patients is tobacco and represents one-fifth of all cancer-related deaths in India.

However, to address the havoc caused by this dreaded disease effectively, India will also need to bridge the huge gap of shortfall in disease diagnostic infrastructure in the country.

The humongous access gap for cancer patients needs to be effectively addressed by the Government sooner with Public-Private-Partnership (PPP) for diagnosis and treatment, in tandem with other proactive initiatives like, disease awareness campaigns targeted to ensure greater screening and disease prevention, wherever possible.

‘The Lancet’ finding:

Following are some of the important findings on cancer disease profile in India, as reported in May 12, 2012, edition of ‘The Lancet’:

-       6 percent of the study deaths were due to cancer

-       71 percent cancer deaths occurred in people aged 30—69 years

-       Age-standardized cancer mortality rates per 100,000 were similar in rural and urban     areas but varied greatly between the states, and were two times higher in the least educated than in the most educated adults.

This report further calls for immediate Government intervention in this area.

Growing patients number making ‘Oncology Market’ increasingly attractive:

As stated above, incidence of various types of cancer is rapidly increasing across the world, making oncology segment an ‘El Dorado’ for many pharmaceutical players prompting commensurate investments for product development in this area, be these are new molecules or biosimilars.

Thus, the global turnover of anti-cancer drugs, which was around US$ 50 billion in 2009, is expected to grow to US$ 75 billion in 2013 registering a jaw dropping growth rate in today’s turbulent global pharmaceutical market environment.

World Health Organization (WHO) has predicted over 20 million new cases of cancer in 2025 against 12 million in 2008.

Globally, the segment growth will mainly be driven by early detection, longer duration of treatment and the global ascending trend in the incidence and prevalence of cancer propelled by new treatments and improved access to cancer therapies in many countries.

Indian business landscape:

Oncology segment has now emerged as a leading therapeutic area in the Indian pharmaceuticals market too, being fourth largest in volume and tenth largest in value term, mainly driven by lower priced generic equivalents in volume term.

Despite only a smaller number of patients can afford any comprehensive cancer treatment protocol in India, the demand for cancer drugs in the country, where many drug companies follow various types of unconventional logistics systems to reach these drugs to patients, is increasing at a rapid pace.

Global players namely, Roche, BMS, Pfizer, Sanofi, GSK and Merck reportedly dominate the market with innovative drugs. Whereas, domestic companies like, Natco Pharma, Cipla, Sun Pharma, Dr. Reddy’s Lab (DRL), Biocon and others are now coming up with low price generic equivalents of many cancer drugs.

The fact that currently over 30 pharmaceutical companies market cancer drug in the country, demonstrates growing attractiveness of the Oncology segment in India.

Access to newer cancer drugs:

It has been widely reported that newer cancer therapies have significant advantages over available generic cancer drugs both in terms of survival rate and toxicity.

Unfortunately such types of drugs cost very high, severely limiting access to their therapeutic benefits for majority of patients. For a month’s treatment such drugs reportedly cost on an average US$ 3,000 – 4,500 or Rs 1.64 – 2.45 lakh to each patient in India.

More R&D investments in Oncology segment:

Another study recently published by ‘Citeline’ in its  ‘Pharma R&D Annual Review 2012’ points out, more than half of the top 25 disease areas targeted for R&D falls under cancer therapy. Breast cancer comes out as the single most targeted disease followed by Type 2 diabetes. 

This will ensure steady growth of the Oncology segment over a long period of time and simultaneously the issue of access to these medicines to a large number of patients, if the product pricing does not fall in line with socioeconomic considerations of India.

Cancer drug sales dominated in 2012: 

It is interesting to note that around one-third of the ‘Top 10 Brands in 2012′ were for the treatment of cancer as follows:

Top 10 global brands in 2012

Rank Brand Therapy Area Company Sales: (US$ bn)
1. Humira Rheumatoid Arthritis and others Abbott /Eisai (now AbbVie/Eisai) 9.48
2. Enbrel Anti-inflammatory Amgen/Pfizer/Takeda 8.37
3. Advair/Seretide Asthma, COPD GlaxoSmithKline 8.0
4. Remicade  Auto-immune Johnson & Johnson/Merck/ Mitsubishi Tanabe 7.67
5. Rituxan Anti-cancer Roche 6.94
6. Crestor Anti-lipid AstraZeneca/ Shionogi 6.65
7. Lantus Anti-diabetic Sanofi 6.12
8. Herceptin Anti-cancer Roche 6.08
9. Avastin Anti-cancer Roche 5.98
10. Lipitor Anti-lipid Pfizer/Astellas Pharma/Jeil Pharmaceutical 5.55

(Source: Fierce Pharma)

Responsible Pricing a key issue with cancer drugs:

In the battle against the much dreaded disease cancer, the newer innovative drugs being quite expensive, even in the developed markets the healthcare providers are feeling the heat of cost pressure of such medications, which in turn could adversely impact the treatment decisions for the patients.

Thus, to help the oncologists to appropriately discuss the treatment cost of anti-cancer drugs with the patients, the ‘American Society of Clinical Oncology’ recently has formed a task force who will also try to resolve this critical issue.

In many other developed markets of the world, for expensive cancer medications, the patients are required to bear the high cost of co-payment. This may run equivalent to thousands of U.S dollars, which many patients reportedly find difficult to arrange.

It has been reported that even the ‘National Institute of Health and Clinical Excellence (NICE), UK’ considers some anti-cancer drugs not cost-effective enough for inclusion in the NHS formulary, sparking another set of raging debate.

‘The New England Journal of Medicine’ in one of its recent articles with detail analysis, also expressed its concern over sharp increase in the price of anti-cancer medications, specifically. 

An interesting approach:

Experts are now deliberating upon the possibility of creating a ‘comparative effectiveness center’ for anti-cancer drugs. This center will be entrusted with the responsibility to find out the most cost effective and best suited anti-cancer drugs that will be suitable for a particular patient, eliminating possibility of any wasteful expenses with the new drugs just for newness and some additional features. If several drugs are found to be working equally well on the same patient, most cost effective medication will be recommended to the particular individual.

India should also explore this possibility without further delay.

Indian Government trying to find an answer in CL/NLEM/NPPP 2012:

Going by the recent developments in Compulsory License (CL) area for high priced new and innovative cancer drugs, it appears that in the times to come exorbitant prices for cancer drugs may prove to be loaded with risks of grant of CL in India due to immense public pressure.

It appears from the grapevine that Government may also explore the possibility to include some of the newer cancer drugs under National List of Essential Medicines (NLEM) bringing them under price control in conformance with the National Pharmaceutical Pricing Policy 2012 (NPPP 2012), if not through the provision of pricing of patented drugs.

Thus responsible pricing of cancer drugs assumes huge importance for avoidance of the above unpleasant situation in India.

Cancer drug pricing related developments in India:

As stated above, cancer being the second largest killer in India and the patented cancer drugs being generally expensive, a large Indian pharmaceutical player has been reportedly insisting on the government to allow widespread use of “compulsory licenses” for cancer drugs. About 11 years ago various news reports highlighted that this company broke ‘monopoly ‘ of the multinationals by offering to supply life-saving triple therapy AIDS drug cocktails for under US$1 a day, which is about one-thirtieth the price of the global companies.

In May 2012, this same Indian company named Cipla, significantly reduced the cost of three medicines to fight brain, kidney and lung cancers in India, making these drugs around four times cheaper than the originators, as per the above news report. The company reportedly wants to reduce the prices of more cancer drugs in future.

Prompted by the above steps taken by Dr. Yusuf Hamied, the Chairman of Cipla, many global players have reportedly branded him as an Intellectual Property (IP) thief, while Dr. Hamied reportedly accused them of being “Global Serial Killers” whose high prices are costing many precious lives across the globe.

In the same interview Dr. Hamied said poverty-racked India “can’t afford to divide people into those who can afford life-saving drugs and those who can’t”.

Promising future potential for low cost newer generic cancer drugs: 
 

While R&D initiatives are going on full throttle for newer and innovative drugs for cancer, interestingly over a quarter of the following 15 brands, which will go off-patent in 2013 are for cancer, throwing open the door for cheaper newer generics entry and increasing access to these medicine for a larger population of cancer patients.

Patent expiry in 2013 

Rank Brand Generic name Therapy Area Company Patent Expiry Sales US$ billion (2012)
1. Cymbalta Duloxetine Antidepressant, musculoskeletal pain Eli Lilly/Shionogi Dec 11 4.9
2. Avonex Interferon beta1a Multiple Sclerosis (MS) Biogen Idec Dec 31 2.9
3. Humalog Insulin lispro Anti-diabetic Eli Lilly May 7 2,52
4. OxyContin Oxycodone Pain Perdue August 31, 2.35
5. Rebif Interferon beta-1a Multiple Sclerosis (MS) Merck KgaA Dec 31 2.3
6. Aciphex Rabeprazole Acid-peptic disorder J&J, Eisai May 8 1.93
7. Xeloda Capecitabin
 Cancer Roche Dec 14 1.63
8. Procrit Epoetin Alfa Anemia J&J Aug 29 1.41
9. Neupogen Filgrastim Cancer Amgen, Kirin, Roche, Royalty Pharma Dec 12 1.29
10. Zometa Zoledronic Acid Cancer Novartis March 2 1.26
11. Lidoderm Lidocaine patch 5% Pain-relieving patch Endo Health Solutions/ EpiCept Sep 15 0.918
12. Temodar Temozolomide Cancer Merck, Bayer Aug 31 0.882
13. Asacol Mesalamine Ulcerative Colitis Warner Chilcott, UCB, Zeria Pharma Jul 30 0.891
14. Niaspan Niacin Anti-lipid Abbott, Teva Sep 20 0.835
15 Reclast Zoledronic acid injection Osteoporosis Novartis March 02 0.612

(Source: Fierce Pharma)

A thought:

Initiatives for faster resolution of a pressing issue like providing affordable treatment for cancer should not be put in the back burner of a longer term planning process. The issue is very real, humanitarian, here and now, for all of us. The Government is expected to display some sense of urgency through its expeditious intervention in all the four of the following treatment processes for cancer to make them affordable, if not free for the general population:

  1. Medical intervention and consultation
  2. Diagnostic tests and detection
  3. Surgical procedure and hospitalization
  4. Medicines and chemotherapy

As ‘The Lancet” study mentions, cancer in India is all-pervasive. It has no rich or poor, urban or rural or even any gender bias. It needs to be addressed in a holistic way for the benefit of all.

Conclusion: 

High incidence of cancer in India with even higher mortality rate, coupled with very high treatment cost has positioned this disease area in the eye of a stormy debate for quite some time. The naked fact that a large number of Indian population cannot afford the high treatment cost for cancer as ‘Out of Pocket’ expenditure, has made the issue even more sensitive and socially relevant in India.

Pricing issue for cancer drugs is not just India centric. Even in the developed countries, heated debate on expensive new drugs, especially, in the oncology segment is brewing up for a while. This could possibly assume a much larger proportion in not too distant future.

It is about time for also the private players to come forward and extend support to the Government in a joint endeavor to tame the destructibility and catastrophic effect of this dreaded disease on human lives, families and the society in general. Setting access improving tangible examples through Public Private Partnership (PPP) initiatives, rather than mere pontification of any kind, is the need of the hour.

If it does not happen, soon enough, willy-nilly the concerned players in this area may get caught in a much fiercer debate, possibly with a force multiplier effect, inviting more desperate measures by the Government.

Responsible pricing, for the patients’ sake, of each element of the cancer treatment process will ultimately assume a critical importance, not just for survival and progress of any business, but also to fetch pots of gold, as business return, from the ‘El Dorado’ of ‘Oncology Segment’ of India.

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.

‘Disease Oriented Treatment’ to ‘Patient Oriented Treatment’ – An evolving trend

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The quest for moving away from conventional and error-prone ‘Disease Oriented Treatment’ paving the way for unconventional individual patient-specific ones, may soon come to fruition. Dramatic progress in the research for developing ‘Personalized Medicines’ could soon offer a choice for individual ‘Patient Oriented Treatment’ with precisely predictable efficacy and safety, especially for the treatment of various intractable and dreaded diseases.

Sir John Bell, Professor of Medicine at Oxford University, adviser on genetics to the government and chair of its human genomics strategy group has reportedly said in early December 2012 that ‘Personalized Medicine’ for all could soon be a clear possibility, as everybody will be able to have their entire DNA make-up mapped for as little as £100 (Rs.8, 700 approx.).

This estimate seems to be quite realistic as Sir John said, the price of genome sequencing has fallen by 100,000-fold in 10 years and genetics being a key component of all common diseases, genome sequencing will help immensely in the use of new drugs, as well.

Raising a flag:

While watching the pursuit of excellence by the genetic scientists in the realm of disease treatment, some experts have reportedly been sounding a note of caution. They strongly feel that DNA code sequencing brings to light a “very real privacy concerns” of individuals.

GeneWatch UK, is an organization that investigate how genetic science and technologies will impact on our food, health, agriculture, environment and society. They have been strongly arguing, if genome sequencing is extended to entire population, individuals and their relatives could then be identified and tracked by matching their DNA with the genome stored in the respective health records. This move, as contemplated by them, could “wipe out privacy” with an impact on the society.

Thus, the ethical and social issues in the development of ‘Personalized medicines’ primarily in the area of genetic testing and consideration of race in the development of such medicines, these thought leaders feel, need to be effectively addressed, sooner.

That said, the Prime Minister of UK Mr David Cameron has reportedly said:

“By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care. We are turning an important scientific breakthrough into a potentially life-saving reality for NHS patients across the country. If we get this right, we could transform how we diagnose and treat our most complex diseases not only here but across the world, while enabling our best scientists to discover the next wonder drug or breakthrough technology.”

Increasingly more in development pipeline:

Rapid strides in pharmacogenomics bring in a promise of radically different ways of treating diseases, as major pharmaceutical companies of the world make progress in developing much more effective medicines designed to target smaller populations.

Tufts Center for the Study of Drug Development (Tufts University) in its publication named ‘Impact Report’, November/December 2010 articulated, “Bio-pharmaceutical companies are committed to researching and developing personalized medicines and within their development pipelines, 12% – 50% of compounds are personalized medicines.”

Experts envisage that over a period of time ‘Personalized Medicines’ will be targeted to biological/genomic profile of a patient or patient types to significantly improve the quality of treatment.

The definition:

The above report defines Personalized Medicines as “Tailoring of medical treatment and delivery of health care to individual characteristics of each patient, including their genetic, molecular, imaging and other personal determinants. Using this approach has the potential to speed accurate diagnosis, decrease side effects, and increase the likelihood that a medicine will work for an individual patient.”

Mainly due to all these reasons, ‘Personalized Medicines’ are expected to be an effective alternative to quite unwieldy current ‘blockbuster drug’ business model.

Makes a perfect fit:

The aim of ‘personalized medicines’ is, therefore, to make a perfect fit between the drug and the patient. It is worth noting that genotyping is currently not a part of clinically accepted routine. However, it is expected to acquire this status in the western world, very shortly.

Consequent changes and shifts:

This potential paradigm shift in the healthcare space would prompt similar changes in various disease diagnostic technologies, which will not only be able to detect a disease well before appearance of symptoms, but would also indicate which patients will best respond to or be adversely affected by which medications.

‘Personalized Medicines’ will in that process ensure a critical shift from the ‘Disease Oriented Treatment’ to a ‘Patient Oriented Treatment’, which can be initiated even before the clinical manifestations of a disease are detected.

The technological march towards this direction is indeed risky and arduous one. However, the benefits that the humanity will accrue out of this disruptive innovation will far outweigh the risks in all forms.

Towards this direction:

  • The Economist, March 12-18, 2011 in its article titled “Toward the 15-minute genome” reported that ‘nanopore sequencing’ of human genome is now gaining momentum. This could make sequencing of entire genome of cancerous and healthy cells possible to accurately point out what has exactly changed in individual patients, enabling the oncologists to determine patient specific drugs for best possible results in each case, separately.
  • New cancer marker has been reported to aid earlier detection of the disease, where repetitive stretches of RNA are found in high concentrations in cancer cells.
  • A new blood test will accurately detect early cancer of all types with an accuracy of greater than 95%, when repeated the accuracy will even be even greater than 99%.
  • ‘Breast On A Chip’ will test nano-medical detection and treatment options for breast cancer.
  • A brain scan will detect the telltale “amyloid plaques” ,the protein fragments that accumulate between nerves in Alzheimer’s disease.

A difference that matters:

With ‘Personalized Medicines’ the health of a patient will be managed based on personal characteristics of the individual, including height, weight, diet, age, sex etc. instead of defined “standards of care”, based on averaging response across a patient group. Pharmacogenomics tests like, sequencing of human genome will determine a patient’s likely response to such drugs.

All these are expected to offer more targeted and effective treatment with much safer drugs, and in all probability at a lesser real cost. Such medicines will also help identify individuals prone to serious ailments like, diabetes, cardiovascular diseases and cancer and help physicians to take appropriate preventive measures, simultaneously.

Each patient is unique:

‘Personalized medicines’ in that process will focus on what makes each patient so unique, instead of going by the generalities of a disease.

To give a quick example, genetic differences within individuals determine how their bodies react to drugs such as Warfarin – a blood thinner taken to prevent clotting. It is of utmost importance to get the dosing right, as more of the drug will cause bleeding and less of it will not have any therapeutic effect.

‘Personalized medicines’, therefore, have the potential to usher in a revolutionary change, the way patients are offered treatment by the medical profession. Genomic research will enable physicians to use a patient’s genetic code to arrive at how each patient will respond to different types of available treatments.

In the field of cancer, genetic tests are currently being done by many oncologists to determine which patients will be benefited most, say by Herceptin, in the treatment of breast cancer.

Indian initiatives:

Some companies, both well known and little known, are making quiet collaborative progress in the genome sequencing area in India, which will ultimately make expensive treatments like cancer more affordable to many.

Other advantages:

The expected benefits from the ‘Personalized Medicines’, besides very early diagnosis as stated above, are the following:

1. More Accurate Dosing: Instead of dose being decided based on age and body weight of the patients, the physicians may decide and adjust the dose of the medicines based on the genetic profiling of the patients.

2. More Targeted Drugs: It will be possible for the pharmaceutical companies to develop and market drugs for patients with specific genetic profiles. In that process, a drug needs to be tested only on those who are likely to derive benefits from it. This in turn will be able to effectively tailor clinical trials, expediting the process of market launch of these drugs.

3. Improved Healthcare: ‘Personalized Medicines’ will enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’ without any trial or error. This would give rise to much better overall healthcare.

Reduced Clinical Trial cost:

Genome sequencing will help identifying a patient population, which will be far more likely to respond positively to the new treatment. In that process, if it reduces costs of clinical trial by even 5%, expected net savings for the industry towards clinical trial in real term will be significant.

With ‘personalized medicines’ the innovator companies will be able to significantly reduce both time, costs and the risks involved in obtaining regulatory approvals and penetrating new markets with simultaneous development of necessary diagnostic tests. Such tests will be able to identify patients group who will not only most likely to be benefited from such medicines, but also will be least likely to suffer from adverse drug reactions.

Therefore, considerable cost advantages coupled with much lesser risks of failure and significant reduction in the lead time for clinical trials are expected to make ‘personalized medicines’ much more cost effective, compared to conventional ‘blockbuster drugs’.

A sustainable business model:

Realization of deficiencies in the deep-pocket economics of ‘block buster drug R&D business model’ has made ‘personalized medicines’ a reality today. Large number of smaller and exclusive markets for ‘personalized medicines’ is also expected to be quite profitable for the pharmaceutical companies. On the other hand, better efficacy and safety profile of ‘personalized medicines’ will prove to be cost-effective in the overall healthcare systems.

However, smaller segmentation of the market may not leave enough space for the conventional ‘blockbuster model’, which is the prime mover of the global pharmaceutical industry, even today.

Reports indicate that some renowned global pharmaceutical companies like, Roche, AstraZeneca, GlaxoSmithKline are making good progress towards this direction through collaborative initiatives.

A different marketing ball game:

With ‘personalized medicines’ the ball game of marketing pharmaceuticals is expected to undergo a paradigm shift. Roche’s model of combining necessary diagnostic tests with new drugs will play a very important role in the new ball game.

Roche is reportedly ensuring that with accompanying required diagnostic tests, the new oncology products developed at Genentech can be precisely matched to patients.

Use in ‘Primary Care’:

Currently there is no widely successful model for use of ‘personalized medicines’ in a ‘primary care’ situation. However, it has been reported that in states like, Wisconsin in the U.S, initiative to integrate genomic medicines with ‘primary care’ has already been undertaken.

Scaling-up operations of such pilot projects will give a big boost to revolutionize the use of ‘personalized medicines’ for precision and targeted treatment for the ailing population.

Current Applications:

Though these are still the early days, initial benefits of ‘personalized medicines’ are now being reported in many areas like:

  • Genetic analysis of patients dealing with blood clots: Since 2007, the U.S. Food and Drug Administration has been recommending genotyping for all patients being assessed for therapy involving Warfarin.
  • Colorectal cancer: For colon cancer patients, the biomarker that predicts how a tumor will respond to certain drugs is a protein encoded by the KRAS gene, which can now be determined through a simple test.
  • Breast cancer: Women with breast tumors can now be effectively screened to determine which receptors their tumor cells contain.

Above applications of ‘personalized medicines’ will help saving not only significant expenses, but also precious time, which is usually spent for ‘trial-and-error treatments’. In addition, this approach also helps clinicians to determine quickly which therapies are most likely to succeed.

A truly patient centric treatment approach:

Generally speaking, unlike conventional ‘one size fits all’ type treatment approach, where same medicine with varying efficacy is tried on a large number of patients with equally varying rates of failure, ‘personalized medicines’ in true sense starts with the patients.

This may not necessarily mean unique treatment for each patient every time. With ‘personalized medicine’-based treatment approach, depending on biological, genetic and genomic characteristics, patients can be divided into groups and targeted treatment with specific drugs showing most efficacy and least side-effects can be worked out for each of these groups. Hence ‘personalized medicines’ by all means are truly patient centric.

Conclusion:

One of the key issues today in the realm of conventional ‘Disease Oriented Treatment’ is that lot many drugs do not work on significantly large number of patients with same efficacy and safety standards. ‘Personalized medicines’ will be able to address this issue with right diagnosis, ensuring treatment with the right medicine in right doses for the right type of patients.

Though in Europe and to some extent in the US, ‘Patient Oriented Treatment’ approaches with ‘personalized medicines’ have already been initiated, these are still early days for this novel concept to get translated into reality for wider use.

Lot many grounds may still need to be covered especially in the areas of medical research and also to work out the regulatory pathways for ‘personalized medicines’ in healthcare by the pioneers of this great concept.

That said, the evolving transition from the conventional ‘Disease Oriented Treatment’ to unconventional ‘Patient Oriented Treatment’ seems to be irreversible now.

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 and also do not contribute to any other blog or website with the same article that I post in this website. Any such act of reproducing my articles, which I write in my personal capacity, in other blogs or websites by anyone is unauthorized and prohibited.