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Hepatitis C: A Silent, Deadly Disease: Treatment Beyond Reach of Most Indians

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Every year, July 28 is remembered as the ‘World Hepatitis Day’. In India, this year too, the day had gone by virtually uneventful, for various reasons. This happened despite increasing trend of the disease in the country.

Though, there are five main hepatitis virus types, namely A, B, C, D and E, of which B and C are the most fatal, in this article, I shall focus mainly on hepatitis C.

According to the World Health Organization (WHO), globally around 150 million people are infected with chronic hepatitis C virus (HCV), which is considered as one of the key factors for liver cirrhosis, fibrosis and hepatocellular carcinoma. At least, 350,000 HCV infected people die annually from these ailments.

A July 2014 study conducted by Metropolis Healthcare reportedly found that 17.97 percent of 78,102 samples studied in major cities of India such as, Mumbai, Delhi and Chennai, were infected with HCV and the patients belonged to the age group of 20 to 30 years. Out of 10,534 the tested sample in the age group of 0 to 10 years, 3,254 samples (30.89 percent) tested positive with HCV.

Institutes of Medicine (IOM) and the Department of Health and Human Services (HHS) of the United States consider hepatitis C infections a “silent epidemic,” as many patients infected with HCV are symptom free, without even leaving any hint to them that they are infected. The infected persons may feel healthy, even when serious liver damage is taking place, sometimes through decades.

All these patients are also potential carriers of HCV, risking rapid spread of the virus, as identification of the infected individuals for remedial measures continue to remain mostly eluding in India.

According to experts, around 80 percent of the HCV patients ultimately develop chronic hepatitis with serious liver damage, causing significant debility. With further progression of the disease, around 20 percent of these patients could develop fatal liver cirrhosis and 5 percent may fall victim of liver cancer.

A situation like this, is indeed a cause of yet another major worry in the healthcare space of India. Deadly hepatitis C crisis would likely to worsen much, if it does not receive healthcare focus of all stakeholders, sooner.

Traditional treatment regime:

There is no vaccine developed for HCV, as yet. HCV usually spreads through sharing of needles, syringes or other equipment to inject drugs, infected blood transfusion and tattooing, among others.

The standard treatment for HCV is interferon-based injections, which could make patients feel ill and give rise to flulike symptoms. Moreover, the treatment with interferon lasts from six months to a year and cures only 40 to 50 of HCV infected patients.

Now, chronic HCV treatment also includes a combination of three drugs – ribavirin (RBV), pegylated interferon (PEG) and a protease inhibitor, such as, simeprevir or boceprevir or telaprevir. These three drug combinations inhibit viral replication for enhancing immune response of the body to hopefully eradicate the virus.

At times, patients with very advanced liver disease may not be able to tolerate this traditional treatment with interferon-based injections, as those could make them feel worse.

The latest development in treatment:

There has been a significant advance in the treatment of HCV patients today with a new drug in the form of tablet that has doubled the viral cure rates from 40 to 50 percent to 90 to 100 percent.

Moreover, the new drug not just enables the physicians switching from injectibles to oral tablet, but at the same time reduces the duration of treatment to just 12 weeks, instead of 6 months to one year, offering a huge advantage to patients suffering from HCV.

This new generation of treatment now includes only Sovaldi (sofosbuvir) of Gilead, which is the first drug approved to treat certain types of hepatitis C infection, without any compelling need to co-administer with interferon.

Some other global pharma majors, such as Bristol-Myers Squibb, Merck & Co, Johnson & Johnson and AbbVie are also developing oral treatment regimens for HCV. All these have shown equally dramatic results in clinical trials, reducing the requirement for debilitating interferon injections.

Allegation of profiteering:

Looking at the high cure rate of more than 90 per cent for much-distressed HCV infected patients, none would possibly dispute that Sovaldi of Gilead signifies a giant leap in the treatment of HCV. But Gilead, according to a ‘Financial Times (FT)’ report, faces strong criticism of alleged ‘profiteering’ for its pricing strategy of this drug.

Sovaldi has been priced by Gilead at Rs 60,000 (US$ 1,000) per tablet with a three-month course costing Rs1.8 Crore (US$ 84,000), when it reportedly costs around U$130 to manufacture a tablet. This treatment cost is being considered very high for many Americans and Europeans too.

“At the US price, Gilead will recoup its Sovaldi development investment  . . . in a single year and then stand to make extraordinary profits off the backs of US consumers, who will subsidize the drug for other patients around the globe”, the FT report states.

This line of argument has been gaining ground on Capitol Hill, as well. This month, two senior members of the US Senate Finance Committee wrote to John Martin, Gilead Chief Executive, asking him to justify Sovaldi’s price, the report mentioned.

Half yearly sales of US$ 5.8 billion came from just 9,000 patients:

Be that as it may, the bottom line is, in the midst of huge global concerns over alleged ‘profiteering’ with this exorbitantly priced HCV drug, Gilead has reportedly registered US$ 5.8 billion in sales for Sovaldi in the first half of 2014.

The company has reportedly noted on its earnings call that it believes 9,000 people have been cured of HCV so far with Sovaldi. This means that the 6-month turnover of Sovaldi of US$ 5.8 billion has come just from 9000 patients. If we take the total number of HCV infected patients at 150 million globally, this new drug has benefited just a minuscule fraction of less than one percent of the total number of patients, despite clocking mind-boggling turnover and profit.

Stakeholders’ pressure building up:

Coming under intense pressure from all possible corners, Gilead has reportedly announced that it has set a minimum threshold price of US$ 300 a bottle, enough for a month. With three months typically required for a full course and taking into account the currently approved combination with interferon, the total cost per patient would be about US$ 900 for a complete treatment against its usual price of US$ 84,000. The company would offer that price to at least 80 countries.

For this special price, Gilead reportedly has targeted mostly the world’s poorest nations, but also included some middle income ones such as Egypt, which has by far the highest prevalence of HCV in the world. In Egypt, about 10 million people remain chronically infected and 100,000 new infections occur each year, according to Egyptian government figures. However, independent surveys  put this number between 200,000 and 300,000. Gilead has already signed an agreement with the Egyptian government in early July 2014 and the drug would be available there in September 2014. This would make Egypt the first to have access to Sovaldi outside the US and the EU.

What about India?

Gilead has reportedly announced, “In line with the company’s past approach to its HIV medicines, the company will also offer to license production of this new drug to a number of rival low-cost Indian generic drug companies. They will be offered manufacturing knowhow and allowed to source and competitively price the product at whatever level they choose.”

This is indeed a welcoming news for the country and needs to be encouraged for expeditious implementation with support and co-operation from all concerned.

Regulatory requirement:

However, despite all good intent, Gilead says, “ Some countries, such as India and China, are not satisfied with the tests conducted in the US and elsewhere for Sovaldi. They want additional clinical trials to be conducted on their own patients as a precondition for authorization, which will add extra costs and delays.”

Patent status:

It is worth noting here that the Indian patent office has not even recognized Sovaldi’s patent for the domestic market.

Local measures to address chronic hepatitis:

On May 22, 2014, the World Health Assembly adopted a resolution to improve prevention, diagnosis and treatment of viral hepatitis, in general. However, as things stand today in India, the surveillance systems for viral hepatitis are grossly inadequate and preventive measures are not universally implemented.

The Union Government of India has now expressed its intent to set up ten regional laboratories through the National Communicable Disease Centre (NCDC) for surveillance of viral hepatitis in the country. The key objective of these laboratories would be to ascertain the burden of viral hepatitis in India by 2017 and to provide lab support for investigating outbreaks.

Government sources indicate, the initial focus would be more on the preventive aspects rather than treatment of viral hepatitis given the limited health resources available. Setting up universal guidelines for immunization along with mass awareness and education have been considered as critical to fight this dreaded disease in the country. Simultaneously introduction of nucleic acid testing (NAT) and standardization of blood bank practices would be undertaken for preventing blood transfusions related viral hepatitis, in general.

Treatment for HCV is not widely available in the country. All types of HCV treatments, especially the newer and innovative ones, must be made available to all infected patients, as these drugs have high cure rates, short duration of treatment and minimal side effects.

Conclusion:

Viral hepatitis in general and hepatitis C in particular are becoming great national health concerns, as these contribute to significant morbidity and mortality, further adding to the national economic burden. India should just not strengthen its prevention strategies; it needs to focus on all the factors that influence speedy diagnosis and treatment of HCV.

As the WHO says, “New drugs have the potential to transform hepatitis C treatment, with safe and simple treatments resulting in cure rates of over 90 per cent”. The raging debate on Sovaldi needs to explore the newer avenues and measures for appropriately pricing the innovative medicines in the days ahead.

Concerned pharma players, the government and other stakeholders must work together and in unison to ensure that all those infected with HCV are diagnosed quickly and have access to life-saving treatments.

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 industry requires striking a right balance between ethical obligations to shareholders and ethical obligations to patients

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On September 15, 2012, while delivering his keynote address in a pharmaceutical industry function, Dr. Sam Pitroda, the Chicago based Indian, creator of the telecom revolution in India and the Advisor to the Prime Minister on Public Information, Infrastructure & Innovations, made a profound comment, for all concerned to ponder, as follows:

“Everyone wants to copy the American model of development.  I feel that this model is not scalable, sustainable, desirable and workable.  We have to find an Indian Model of development which focuses on affordability, scalability and sustainability.”

The above comment assumes greater significance, as the U.S. has been the number one pharmaceutical market of the world over a long period of time, although currently growing at a snail’s pace, as compared to the emerging markets of the world or even in absolute numbers.

Being impressed by past success record of America in the pharmaceutical sector, many countries of the world are being influenced to imbibe the U.S. models in various areas of the industry like, R&D, product commercialization process, focus on the “Wall Street” and even the way America walks the talk in fulfilling its various ethical obligations.

As the popular saying goes ‘proof of the pudding is in the eating’, gradual drying-up of the R&D pipeline, significant decline in the pharmaceutical business growth rate with commensurate adverse impact on the “Wall Street” and regularly published media reports on ‘unethical marketing practices’, lead to pertinent questions on the longer-term sustainability of the U.S. model in all these areas.

It appears, prompted by the prevailing reality in the U.S since quite some time, Dr. Pitroda made the above comment in a wider context of the pharmaceutical industry, including very important scalability, sustainability, desirability and workability of the ethical values in the Indian pharmaceutical business operations.

A burning issue:

As stated above, even in areas related to ethical issues in the pharmaceutical industry, global media reports indicate, as Dr. Pitroda commented above, the American model has not been successful to set an example for others, as yet. Thus, here also India will possibly need to find an Indian model that works and is sustainable.

We have been witnessing, for quite some time from now, among many other burning issues, ethical concerns related to the pharmaceutical industry across the world, have been hugely bothering a large section of its stakeholders, solely for the interest of patients and India is no exception to this stark reality.

Such concerns emanate from widely circulated media reports on legal fines levied to large pharmaceutical companies or out of court settlements on such fines due to alleged ‘unethical’ business practices of some large companies in various parts of the world including India.

Civil Society and other stakeholders including governments do allege that the prescription decisions made by the doctors, having received expensive free products and services from the pharmaceutical companies may not entirely or always be in the best interest of the patients.

In a situation like this, overall robust and healthy bottom line of the pharmaceutical industry in general, may be a tad lesser now, calls for a proper balancing act between its ethical obligations to shareholders and the ethical obligations to patients of all class, creed and color together with the civil society, at large.

Unique situation for the patients:

Healthcare sector in general and the pharmaceuticals in particular is unique in many respects. The Department Related Parliamentary Committee on Health and Family Welfare in its 59th Report clearly articulated that:

Medicines apart from their critical role in alleviating human suffering and saving lives, have very sensitive and typical dimensions for a variety of reasons. They are the only commodity for which the consumers have neither a role to play nor are they able to make any informed choices except buying and consuming whatever is prescribed or dispensed to them because of the following reasons:

  • Drug regulators decide which medicines can be marketed
  • Pharmaceutical companies either produce or import drugs that they can profitably sell
  • Doctors decide which drugs and brands to prescribe to their patients
  • Patients are totally dependent on and at the mercy of external entities to protect their interests.

Such a scenario gives rise to a situation where patients, by and large, are compelled to buy medicines at any price, which leads many to conclude that the pharmaceutical industry is ‘recession proof’.

The perspective of the Global Pharmaceutical industry:

The global pharmaceutical industry is primarily research driven, as the low cost generic drugs flow from the patent expiry of innovative drugs. Moreover, the R&D process is arduous, expensive (reportedly costs over US$ 1.8 billion), risky and quite lengthy involving, besides others:

  • Discovery and development process of the New Chemical Entity (NCE) or New Molecular Entity (NME)
  • Pre-clinical trials
  • Clinical trials, Phase I, II and III and IV
  • Stringent marketing approval process

Thus they believe that to foster innovation to meet the unmet needs of patients, the Intellectual Property Rights (IPR) of such products must be strongly protected by the governments of all countries putting in place a robust product patent regime.

Further, the industry strongly argues that to recover high costs of R&D and manufacturing of such products together with making a modest profit, the innovator companies set a product price, which at times may be perceived as too high for the marginalized section of the society, where government intervention is required more than the innovator companies.

Aggressive marketing activities, during the patent life of a product, are essential to gain market access to such drugs for the patients.

In support of the pharmaceutical industry the following argument was put forth in a recent article:

“The underlying goal of every single business is to make money. People single out pharmaceutical companies for making profits, but it’s important to remember that they also create products that save millions of lives.”

Marketing expenditure becoming more productive than R&D investments:

It is indeed interesting to note that expenditure towards marketing by the pharmaceutical companies is becoming more productive than the same towards R&D. This is vindicated by the article titled “R&D and Advertising Efficiencies in the Pharmaceutical Industry”,  published in the International Journal of Applied Economics, 8(1), March 2011.

In this research study the authors stated that although advertising as a percentage of sales has not increased during the past twenty years, its effectiveness in generating sales has improved dramatically by way of the Direct-To-Consumers-Ads (DTCA) strategy, which encouraged patients asking their healthcare providers for brand name drugs rather than cheaper generics. The paper also supports the notion that advertising replaces R&D investments when those investments fail to live up to their promise.

Many experts opine that the above scenario is prevailing today, especially when the global innovator companies are passing through a ‘patent cliff’.

Marketing expenditure far exceeds investments in R&D:

Another article concludes through its research paper titled, “The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States” that pharmaceutical companies spend almost twice as much on promotion as they do on R&D, quite contrary to the claim by the industry.

The study endorses the public image of the pharmaceutical industry as a marketing-driven sector when it should invest more for research and development and much less for promotion, that too many a times is not ‘ethical’ in nature, as cited above.

Patients are the ultimate victims:

A relatively recent report on India dated January 11, 2011, published in ‘The Lancet’, which vindicates the fact, in a similar (though not the same) context, that the alleged ‘unholy relationships’ between many pharmaceutical companies and the doctors, as a result of such aggressive and alleged ‘unethical’ marketing practices, has resulted in over-prescribing and irrational use of injection and drugs causing hardships to the patients.

Conclusion:

As stated above, many experts have been arguing since long, based on available data, that the current business models of many pharmaceutical companies are heavily tilted towards their obligation to the shareholders. These thought leaders are increasingly raising their voices to put forth the view that the industry continues to live in a self-made and a fire-walled cocoon, always trying to change others and refusing to change itself, unfortunately, even for the patients’ sake.

Despite the experts making above comments, my personal view is that in this direction, we have been witnessing no better attitude from our own government either to usher in a much desirable and long pending change in the prevailing scenario, solely for the patients, which is indeed even more disappointing.

In a situation like this, to be ‘patient centric’ in a real sense, there is an urgent need for the industry to first walk the talk along with their respective voluntarily codes of ethical marketing practices both in the letter and spirit.

If voluntary mechanism fails to work, a legal or statutory mechanism should be implemented, like what the Department of Pharmaceuticals had articulated in its draft ‘Uniform Code of Pharmaceutical Marketing Practices’, last year.

Thus, I reckon, to enhance its image, the pharmaceutical industry in India, as advised by Dr. Sam Pitroda, should imbibe a transparent, workable, scalable, demonstrable and a sustainable business model to strike a right balance between its ethical obligations to shareholders and ethical obligations to patients of all class, creed and color together with the civil society, at large

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 New Drug Policy of India enters into the final lap of a Marathon Run

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Final working out and thereafter announcement of much awaited and long overdue the new ‘Drug Policy’ of India has now entered into a very interesting stage. This is mainly because of the unique combination of the following three key reasons:

1. 2002 Drug Policy was challenged in the Karnataka High Court, which by its order dated November 12, 2002 issued stay on the implementation of the Policy. This order was challenged by the Government in the Supreme Court, which vacated the stay vide its order dated March 10, 2003 but ordered as follows: “We suspend the operation of the order to the extent it directs that the Policy dated 15.2.2002 shall not be implemented. However we direct that the petitioner shall consider and formulate appropriate criteria for ensuring essential and lifesaving drugs not to fall out of the price control and further directed to review drugs, which are essential and lifesaving in nature till 2nd May, 2003”.

2. A live court case on the new draft ‘Drug Policy’ with the ‘essentiality criteria’ for price control is pending before the Supreme Court of India with its next hearing scheduled in the last week of July 2012. In this court case an independent network of several ‘Non-Government Organizations (NGOs)’ known as ‘All India Drug Action Network (AIDAN)’ is arguing against the ‘flawed’ draft ‘National Pharmaceutical Pricing Policy 2011 (NPPP 2011)’, mainly on the following grounds:

  • ‘Market Based Pricing (MBP)’ methodology calculated on the ‘Weighted Average Price (WAP)’ of top three brands, as specified in the ‘Draft NPPP 2011’ would not only lead to increase in the prices of medicines, but also legitimize higher drug prices.
  • To keep the drug prices under check effectively, the ‘Ceiling Prices (CP)’ of Medicines should be based on ‘Cost based Pricing (CBP)’ model rather than MBP.
  • Adequate control mechanism is lacking in the NPPP 2011 to prevent the manufacturer from avoiding price control by tweaking with the formulations featuring in the National list of Essential Medicine 2011 (NLEM 2011).

3. In this scenario, a Group of Ministers (GoM) of the Union Cabinet has started deliberating on this issue since April 25, 2012 taking all key stakeholders on board to give its recommendations to the Union Cabinet on the scope, form, structure and the basic content of the new Drug Policy.

The bone of contentions:

The methodology and the span of price control of the draft NPPP 2011 have still remained the key bone of contentions for the new ‘Drug Policy’ of India. Suggested three key methodologies: From the responses received on the draft NPPP 2011, it appears that following three are the  suggested key methodologies to arrive at the CP of price controlled NLEM 2011 formulations:

  • Cost Based Pricing
  • Market based pricing

-  WAP of top 3 brands             -  WAP of bottom 3 brands

  • The formula suggested by the Economic Advisory Council of the Prime Minister of lesser of (i) the price paid by the median consumer + 25% and (ii) price paid by the 80th percentile consumer.

ARGUMENTS IN FAVOR AND AGAINST OF EACH: A. Cost based Pricing: Besides AIDAN, other reported key supporters of the CBP are the Ministry of Health and All India Chemists Associations. ARGUMENTS IN FAVOR: The current drug price control regime (DPCO 1995) is based on cost-plus pricing model, where Maximum Retail Prices (MRPs) of price controlled formulations are worked out as per the formula given in ‘para 7’ of DPCO, 1995 as follows: R.P. = [M.C. +C.C. +P.M. +P.C.] x [1+MAPE/100] +E.D. Where,

  • R.P:  Retail price
  • M.C:  Material cost, including process loss
  • C. C.: Conversion cost
  • P.M: Packing material
  • P.C: Packing Charges
  • MAPE : Maximum Allowable Post manufacturing Expenses of 100 percent
  • E.D.: Excise duty

The proponents of CBP believe that it is:

  • Transparent
  • Most beneficial to the patients
  • Fair, with a decent profit margin allocation for the manufacturers

ARGUMENTS AGAINST: Many others do not believe in CBP. They argue that price-inflation of non-price controlled drugs is much less than the price-controlled ones, which clearly vindicates that market competition works better than price control of drugs and thus is more beneficial to the patients. The following table shows the trend of general inflation against the drug price inflation from 1992 to 2011 period, as follows:

Type of Inflation

Inflation (in Index)
1. General Inflation

403
2. Price-controlled molecules

151
3. Non Price-Controlled Molecules

112

(Source: IMS data, RBI CPI average yearly inflation) This school of thought quotes the example of discontinuation of manufacturing in India 29 out of 74 Active Pharmaceutical Ingredients (APIs) under DPCO 1995 due to financial non-viability on account of CBP. Moreover, CBP is considered by them as a process, which is:

  • Intrusive
  • Lacking in transparency
  • Discretionary
  • Discouraging for innovation, high quality & efficiency
  • Not followed by any major country in the world
  • Not supported by even WHO. It says other countries are moving away from Indian type of CBP

B. Market Based Pricing (MBP): MBP in general is considered by its proponents as a system which is:

  • Transparent
  • Non-Discretionary
  • Encourages growth & investment
  • Rewards innovation
  • Promotes efficiency

The two variants of MBP under discussion are:

- WAP of top 3 brands

- WAP of bottom 3 brands

ARGUMENTS IN FAVOR:

1. WAP of top 3 brands:

  • It is a transparent system and will reduce the prices of medicines
  • With adequate checks and balances in place the method will not lead to increase in prices because of the following reasons:

- All price increases are subject to WPI              – Market competition will not permit any price increases              – Companies in low-price segments will create pressure to reduce prices further

2. WAP of bottom 3 brands: This group argues that instead of WAP of top 3 brands, if the same for the bottom three brands is considered, ceiling prices will come down very significantly, benefiting patients much more than what WAP of top three brands will do.

ARGUMENTS AGAINST:

1. WAP of top three brands:

  • Would lead to overall increase in the prices of many medicines
  • Below ceiling price brands would raise their price upto the ceiling price level immediately
  • Would legitimize high drug prices

2. WAP of bottom 3 brands:

  • Not representative of the market, as only the brands with a low market presence will be considered for WAP calculations
  • The Bottom 3 priced brands factor in only ~17% of the market
  • Likely to have an adverse overall impact on patients as many small brands with lowest acceptable quality standards will be considered for WAP calculations, which may ultimately push high quality formulations out of the market.

C. Formula suggested by EAC of the Prime Minister: ARGUMENTS IN FAVOR:

Will ensures affordable drug prices for the patients by:

  • Encouraging and rewarding high market competition
  • Discouraging monopolistic or oligopolistic market situation

ARGUMENTS AGAINST:

  • EAC criteria for insufficient competition are based on the 1994 Policy
  • The situation is different today as the market has grown 9 times since then
  • The number of brands tends to be low in lower volume turnover molecule segments mainly due to low disease prevalence. Thus bringing these molecules under CBP will be irrational
  • Instead of implementing CBP where lesser number of brands exists in many generic segments, EAC formula should encourage competition even in these lower value turnover molecule segments to bring the prices further down

That said, ‘Drug Price’ has always remained one of the critical factors to ensure greater access to medicines, especially in the developing economies like India, where predominantly individuals are the payors. This point has also been widely accepted by the international community, except perhaps by the diehard ‘self-serving’ vested interests. Important Points to Ponder:

A. ‘Drug Price’ control alone can not improve access to medicines significantly:

To improve access to medicines, even the Governments in countries like Germany, Spain, UK, Korea and China have recently mulled strict price control measures in their respective countries. However, it is important to note and as we have seen above, though the drug prices are indeed one of the critical factors to improve access to modern medicines, there is a need to augment other healthcare access related initiatives in tandem for a holistic approach.

In India, we have witnessed through almost the past four decades that drug price control alone  could not improve access to modern medicines for the common man very significantly, especially in the current socioeconomic and healthcare environment of the country.

B. Taming drug price inflation only has not helped improving access to medicines:

It is quite clear from the following table that food prices impact health more than medicine costs :

Year

Pharma Price Increases

Food Inflation

2008

1.1%

5.6%

2009

1.3%

8.0%

2010

0.5%

14.4%

Source: CMIE Exploring a practical approach: Considering pros and cons of the key methodologies of price control of formulations featuring in NLEM 2011, as I had written in this blog in April 2, 2012, I would like to reemphasize that a middle path with a win-win strategy to resolve this deadlock effectively would be in the best interest of both patients and the industry alike, in the current situation. The middle path, I reckon, may be explored as follows:

  1. Calculate ‘Weighted Average Price’ for each formulation based on prices of all brands – high, medium and low, applying some realistic exclusion criteria.
  2. When inclusion criteria for price control in the draft NPPP 2011 is ‘essentiality’ of drugs, it sounds quite logical that price control should be restricted to NLEM 2011 only.
  3. Enough non-price control checks and balances to be put in place to ensure proper availability of NLEM 2011 drugs for the common man and avoidance of any possible situation of shortages for such drugs.

Conclusion:

Conforming to the directive of the honorable Supreme Court of India on price control of essential medicines in the country, the GoM should now help resolving the issue of putting in place a robust new National Pharmaceutical Pricing Policy, without further delay, taking the key stakeholders on board.

In any case, it has to be a win-win solution both for the patients and the industry alike, paving the way for improving access to modern medicines for the entire population of India, together with other strategic initiatives in this direction. This is absolutely essential, especially when medicines contribute around 72 percent of the total ‘Out of Pocket Expenses’ of the common man of the country.

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 New Drug Policy is languishing in a labyrinth

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Drug Price Control has remained the key feature of all Drug Policies of India, since their inception in early 70’s. Most of these policies continued to remain behind their times consistently, without any exception.

That said, the Drug Policy 1994 and the consequent Drug Price Control Order 1995 (DPCO  ’95) have now become the largest ‘Dinosaur’ of all Drug Policies. However, the most intriguing point though, both these have still been kept operational by the government and the very concept of a new and a more contemporary one is languishing in a labyrinth since over a decade, for reasons of anybody’s guess.

Drug Price Control system in India:

It appears that the drug price control system in India is here to stay, at least in the short to medium term and that too in a seemingly best case scenario.

The key reasons:

As we know, the key reasons of price control for pharmaceuticals in India are the following:

  • To contain cost of medicines, particularly the essential ones, at a reasonably affordable level, which is a very important part of the total healthcare expenditure of the common man.
  • To provide greater access to medicines to all, especially in view of very high  ‘out of pocket expenditure’ for health for a vast majority of population in the country.

The economic factors:

Some of the economic factors, which may cause impediments in achieving these objectives are the following:

  • Sub optimal public healthcare infrastructure, leaky delivery system and high cost of  private healthcare services
  • This is fueled by, as stated above, unabated increase in ‘out-of-pocket expenses’ on healthcare in general and medicines in particular at 78 per cent, as compared to 61 per cent in China, 53 per cent in Sri Lanka, 31 percent in Thailand, 29 per cent in Bhutan and 14 per cent in Maldives (Source: The Lancet)
  • High expenses on drugs for outpatient care

Though very important, drug cost alone, however, does not determine quality of access to healthcare.

Global scenario for drug price control:

As per published reports, all 34 developed nations of the world have ‘Universal Health Coverage’ mechanism in place in various different forms, including mandatory medical insurance requirements, to effectively address the issue of high access to healthcare including pharmaceuticals in their respective countries, significantly reducing ‘out of pocket expenses’ towards health.

All these 34 countries belong to ‘Organization for Economic Co-operation and Development (OECD)’, the governments of which, in some way or the other control and regulate drug prices.

The Governments/payors of most of these countries implement the price control measures by playing the role of a dominant market force directly, while negotiating a favorable price from the manufacturers, which are much lower than their equivalent free market prices.

Many other OECD governments set the drug reimbursement prices right at the time of introduction of new drugs through hard negotiation, which are also well below free market prices and acts as the bench mark market prices, in many ways.

In addition to all these mechanisms, the governments in many OECD countries periodically reduce the prices of already marketed drugs quite significantly.

A contrarian view on Drug Price Control:

Some industry experts feel that there is a hidden consequence for the ‘Drug Price Control System’, especially with the cost based one.

The cost based price control as is currently practiced by the government in India compels the pharmaceutical manufacturers to restrict to:

  • Minimum acceptable quality standard rather than maximum possible quality standards for the patients
  • Does not encourage innovation in formulation development like novel galenic formulations for better patient acceptance and compliance
  • Indirectly discourage innovation in product packaging
  • Ceiling Price mechanism does not encourage advanced anti-counterfeit measures for patients’ safety

These experts also feel that adverse consequences of price control will have a significant negative impact on the pharmaceutical players to plough back fund towards R&D projects to meet the unmet needs of the patients and thereby reducing the range of treatments that could be made available to the patients in the years ahead.

What is China doing?

On March 28, 2011 Reuters reported that China had cut the maximum retail price for more than 1,200 types of antibiotics and the drugs for the circulatory system by an average of 21 percent.

It has also been reported that the Chinese Government has put a cap on the prices of about 300 drugs featuring in their ‘National List of Essential Medicines (NLEM).’

Supreme Court directive on ‘Price Control’ of ‘Essential Medicines’:

It is worth noting in this context that in 2003, the Supreme Court of India, while setting aside the Drug Policy 2002 directed the government to work out effective mechanism to bring all essential and life-saving medicines under price control.

HLEG recommends ‘Price Control’ of ‘Essential Medicines’:

Even in its report the ‘High Level Expert Group (HLEG)’ on ‘Universal Health Coverage (UHC)’ in India, set up by the Planning Commission of India under the chairmanship of the well-known medical professional Prof. K. Srinath Reddy, under recommendation no. 3.5.1, postulated price control and price regulation on essential drugs, which is quite in line with the draft National Pharmaceutical Pricing Policy 2011 (NPPP 2011).

The HLEG report says:

“We recommend the use of ‘essentiality’ as a criterion and applying price controls on formulations rather than basic drugs. Direct price control applied to formulations, rather than basic drugs, is likely to minimize intra-industry distortion in transactions and prevent a substantial rise in drug prices. It may also be necessary to consider caps on trade margins to rein in drug prices while ensuring reasonable returns to manufacturers and distributors. All therapeutic products should be covered and producers should be prevented from circumventing controls by creating nonstandard combinations. This would also discourage producers from moving away from controlled to non-controlled drugs. At the same time, it is necessary to strengthen Central and State regulatory agencies to effectively perform quality and price control functions.”

Types of drug price regulations in India:

  1. Cost based price control: e.g. as specified in the Drug Price Control Order 1995 (DPCO 95)
  2. Marked based price control: e.g. as was suggested by ‘The Pronab Sen Committee’ in 2005
  3. Price Monitoring with a cap on annual price increase: e.g. as is currently followed by the National Pharmaceutical Pricing Authority (NPPA) for all products which are outside DPCO ’95

The weaknesses of cost based pricing mechanism:

The key criticism of cost based pricing mechanism flows from the following arguments:

  • This system is not followed by any developed or developing countries worth mentioning, which follow drug price control mechanism in any form
  • A Complex, intrusive and inefficient system of pricing medicines
  • Does not consider important variations in the level of GMP standards and the quality of input costs
  • The conversion cost and packing norms are determined through a sample survey of less than one per cent of pharmaceutical manufacturing units

Pronab Sen Committee report – the basis of price control in the draft NPPP 2011:

The draft NPPP 2011 is based on the ‘Recommendations of the Task Force constituted under the Chairmanship of Dr. Pronab Sen to explore issues beyond Price Control to make available Life-saving Drugs at reasonable prices’ to all.

‘Pronab Sen Committee’ suggested the following principles of Price regulation to achieve part of the above objective:

1.       The National List of Essential Medicines (NLEM) should form the basis of drugs to be considered for intensive price monitoring, ceiling prices and for imposition of price controls, if necessary.

2.       The government should announce the ceiling price of the drugs contained in the NLEM (other than the drugs procured by hospitals directly and which an individual does not have to purchase from the market) on the basis of the weighted average prices of the top three brands by value of single ingredient formulations prevailing in the market as on 01.04.2005. In cases where there are less than three brands, the weighted average of all the existing brands would be taken. The Org–IMS data set can be used for this purpose initially with a 20 per cent retail margin provided. There is, however, a need to improve the available data coverage, which should be taken up with ORG-IMS or any other data provider.

3.       For drugs which are not reflected in ORG-IMS data, the NPPA should prepare the necessary information based on market data collection.

4.       During the transition period (i.e. till the time ceiling prices are fixed and notified) prices of all essential drugs may be frozen.

5.       The Government should specify the reference product in terms of strength and pack size for each product which would form the basis for price determination. The price ceiling would be specified on a per dosage basis, such as per tablet/per capsule or standard volume of injection. Where syrups and liquids are sold in bottles the ceiling price may be fixed on individual pack size.

6.       Price relaxations may be permitted for non-standard delivery systems, packaging and pack sizes through applications to the negotiations committee, which should become applicable for all similar cases.

7.       In the case of formulations which involve a combination of more than one drug in the NLEM, the ceiling price would be the weighted average of the applicable ceiling prices of its constituents.

8.       For formulations containing a combination of a drug in the NLEM and any other drug, the ceiling price applicable to the essential drug would be made applicable. However, the company would be free to approach the price negotiations committee for a relaxation of the price on the basis of evidence proving superior therapeutic effectiveness for particular disease conditions.

9.       In order to determine the reasonableness of the ceiling prices fixed as above, the prices quoted in bulk procurement by Government and other designated agencies may be examined for use, provided that the system of bulk procurement meets certain minimum prescribed standards. Recognizing that retail distribution has costs not reflected in bulk procurement, a markup of 100 per cent over this reference price is recommended.

10.    NPPA should set up a computer based system which would scan the price data provided by companies against the ceiling prices determined as above and identify formulations which breach the relevant price ceiling. The company manufacturing or marketing such a product would be required to reduce its price or to face penal action.

11.    Companies should be permitted to represent for any price increase on valid grounds, which should then become applicable to the entire class of products.

12.   The NLEM should be revised periodically, say every 5 years, in order to reflect new drugs and significant changes in pattern of drug sales within the therapeutic categories. However till the time the new list is finalized the existing list will continue to be valid for the purpose of price control.

13.   In the case of drugs not contained in the NLEM, intensive monitoring should be carried out of all drugs falling into a pre-specified list of therapeutic categories. Any significant variation in the prices (say above 10 per cent) would be identified for negotiation.

The stakeholders’ comments on NPPP 2011:

About 60 stakeholders have commented by now on the draft NPPP 2011. The views are quite divergent though. It is interesting to note that the new draft pricing policy, in its current form, has been rejected by all key stakeholders, like the Industry, Ministry of Health, Expert Groups, WHO, NGOs and reportedly even by the Economic Advisory Council of the Prime Minister, on quite different grounds.

As widely reported in the media, the pharmaceutical industry, though in favor of the marked based pricing  mechanism, feels that the draft NPPP 2011 will increase the span of drug price control to over 60 per cent of the Indian Pharmaceutical Market (IPM). This means over eight times increase in the span of price control from its current level, making the task unwieldy for even the NPPA.

Majority of other stakeholders including the Ministry of Health, on the contrary, are arguing in favor of cost based price control. They commented that the price control system of the draft policy would give legitimacy to high drug prices in India, leading to increase in the overall prices of medicines. This group feels that the top three brands in majority of cases will be the most expensive ones.

Two interesting observations by the World Health Organization (WHO) on ‘Trade Margin’:

The WHO  in their observations on the draft NPPP 2011 has made the following interesting comments:

  1. “The new price regulation uses a margin of16% to calculate the retail prices. This is a lower margin than currently – based on the market data 1.1 and 3.3 I calculated a current retail margin of 22%. So the new price regulation implies a margin reduction of 6%, alternatively the CP might be set at a 6% lower price than currently is the case.”

If the WHO observation is correct, there is a scope to reduce the price of essential medicines by 6 per cent only through proper regulation of the trade margin.

  1. WHO also comments that IMS data, the basis of all such calculations by the NPPA, has severe limitations as “Their data does not take into account the discounts, rebates and bundling deals and when the data is collected at the level of the wholesaler they estimate the retailer and patient prices”.

If such is the case, what could possibly be the basis of all calculations as captured in the draft NPPP 2011? 

Observation of a distinguished Parliamentarian: 

Dr. Jyoti Mirdha , a Member of the Lower House of the Parliament (Lok Sabha) commented as follows:

“Under this policy the weighted average of three top selling brands will be the ceiling price. There is no logic in restricting the formula to just three brands. Why not five? Why not 10 to arrive at a more representative and reasonable figure? Besides why base on sales figures? In any pricing policy the parameter should be the price. Why not weighted average of 10 least priced brands?”

This could well be a pertinent question.

How to break the logjam now?

Taking on from Dr. Mirdha’s argument , WHO observations and Pronab Sen Committee report, one could possibly try to resolve this logjam by exploring various other available alternatives like for example, the following broad points, to ascertain whether a win-win situation can be created for all through the new drug policy:

  1. What happens if ‘Weighted Average Price’ is calculated based on all brands, instead of top three or bottom three with some exclusion criteria, if required?
  2. When inclusion criteria for price control in the new draft NPPP 2011 is ‘essentiality’ of drugs, it sounds logical that price control should be restricted to National List of Essential Medicines 2011 (NLEM 2011). Only possible extension could perhaps be taking the entire molecule, instead of specified strengths of the same molecule.
  3. Enough non-price control checks and balances to be put in place to ensure proper availability of NLEM 2011 drugs to the common man and avoidance of any possible situation of shortages for such drugs.
  4. As commented by WHO, trade margin should be rationalized, the MRP needs to be reduced accordingly and the consequential benefits to be passed on to the patients.

Conclusion:

The issue of the new National Pharmaceutical Pricing Policy should be resolved sooner than later and that too by conforming to the directive given by the Supreme Court on essential medicines. At the same time, all the stakeholders must feel comfortable with the new drug policy.

The four points, as mentioned above, are just an illustration for choosing an alternative solution. If it works, let us move on. If it does not, let us search for the pathfinder who can break the decade old labyrinth rather quickly, without losing the way yet again.

However, the bottom-line remains that the solution should be a win-win one, both for the patients and the industry alike, benefiting the healthcare space of the country in the years ahead.

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.

Getting unfolded a global opportunity for India with Biosimilar Drugs

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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.

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.

Health being a basic human right, the proposal for ‘Universal Health Coverage’ augurs well for India

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“The right to health is relevant to all States: every State has ratified at least one international human rights treaty recognizing the right to health. Moreover, States have committed themselves to protecting this right through international declarations, domestic legislation and policies, and at international conferences.”

-  The Factsheet, Office of the United Nations High Commissioner for Human Rights (OHCHR) and the WHO

Universal Health Coverage or Universal Healthcare:

In this context, “Universal Health Coverage (UHC)” is a healthcare system where all citizens of a country are covered for the basic healthcare services. In many countries UHC is also known as “Universal Healthcare” and may have different system types as follows:

Single Payer: The government provides insurance to all citizens.

Two-Tier: The government provides basic insurance coverage to citizens and allows purchase of additional voluntary insurance whenever a citizen wants to.

Insurance Mandate: The government mandates that insurance must be bought by all its citizens, like what happened in the USA in 2010.

Global scenario for UHC:

As per published reports, all 33 developed nations have UHC in place. The United States was the only exception until recently, till President Barack Obama administration implemented the ‘path breaking’ new healthcare reform policy in the country in 2010 against tough political opposition.

The new healthcare reform measures in the US had raised a storm within the local pharmaceutical industry, as well,  at that time for various reasons.

The countries providing UHC:

Based on an article titled, ‘ Analyzing our economy, government policy and society through the lens of cost-benefit’ published in  ‘True Cost’ following is the list of the countries where UHC is currently in place:

Country

Start Date of Universal Health Care

System Type

Norway

1912

Single Payer

New Zealand

1938

Two Tier

Japan

1938

Single Payer

Germany

1941

Insurance Mandate

Belgium

1945

Insurance Mandate

United Kingdom

1948

Single Payer

Kuwait

1950

Single Payer

Sweden

1955

Single Payer

Bahrain

1957

Single Payer

Brunei

1958

Single Payer

Canada

1966

Single Payer

Netherlands

1966

Two-Tier

Austria

1967

Insurance Mandate

United Arab Emirates

1971

Single Payer

Finland

1972

Single Payer

Slovenia

1972

Single Payer

Denmark

1973

Two-Tier

Luxembourg

1973

Insurance Mandate

France

1974

Two-Tier

Australia

1975

Two Tier

Ireland

1977

Two-Tier

Italy

1978

Single Payer

Portugal

1979

Single Payer

Cyprus

1980

Single Payer

Greece

1983

Insurance Mandate

Spain

1986

Single Payer

South Korea

1988

Insurance Mandate

Iceland

1990

Single Payer

Hong Kong

1993

Two-Tier

Singapore

1993

Two-Tier

Switzerland

1994

Insurance Mandate

Israel

1995

Two-Tier

United States

2010

Insurance Mandate

Highest per capita health spending has no relevance to the quality of health services/ outcome, but early implementation of UHC has:

The following table shows, although per capita spending on health is the highest in the US, the number of doctors, nurses and hospital beds per 10,000 population are highest in Cuba, UK and Japan, respectively. Japan also records the highest life expectancy at birth.Thus it appears, by and large, those countries which have an efficient UHC scheme running since quite some time from now are doing better in the health parameters as indicated below, especially, as compared to the US with the highest per capita health spending.

Country

Per capita spending on health (US $)

Doctors/ 10,000 pop

Nurses and midwives/ 10,000 pop

Hospital beds/10,000 pop

Life expectancy at birth
USA

    6719**

26

94

31

78
UK

2815

23

  128**

39

80
Russia

698

43

85

97

66
Japan

2581

21

95

  140**

   83**
Italy

2631

37

72

39

82
Germany

3465

34

80

83

80
France

3420

34

80

73

81
Cuba

674

     59**

74

49

78
China

216

14

10

22

74
Canada

3673

19

101

34

81

** Highest

Source: The Guardian, Data Blog, Facts are Sacred)

The current situation in India:

In October 2010, the Planning Commission of India constituted a ‘High Level Expert Group (HLEG)’ on Universal Health Coverage (UHC) under the chairmanship of the well-known medical professional Prof. K. Srinath Reddy. The HLEG was mandated to develop ‘a framework for providing easily accessible and affordable health care to all Indians’.

The HLEG Report starts with:

“This report is dedicated to the people of India whose health is our most precious asset and whose care is our most sacred duty.”

The HLEG defined UHC for India as follows:

“Ensuring equitable access for all Indian citizens, resident in any part of the country, regardless of income level, social status, gender, caste or religion, to affordable, accountable, appropriate health services of assured quality ( promotive, preventive, curative and rehabilitative) as well as public health services addressing the wider determinants of health delivered to individuals and populations, with the government being the guarantor and enabler, although not necessarily the only provider, of health and related services”.

Ten principles for UHC in India:

Following are the ‘Ten Principles’, which guided the HLEG for the formulation of the recommendations for the UHC in India:

  1. Universality
  2. Equity
  3. Non-exclusion and non-discrimination
  4. Comprehensive care that is rational and of good quality
  5. Financial protection
  6. Protection of patients’ rights that guarantee appropriateness of care, patient choice, portability and continuity of care
  7. Consolidated and strengthened public health provisioning
  8. Accountability and transparency
  9. Community participation
  10. Putting health in people’s hands

UHC guarantees access to essential free health services for all:

Because of the uniqueness of India, HLEG proposed a hybrid system that draws on the lessons learned from within India as well as other developed and developing countries of the world.

UHC will ensure guaranteed access to essential health services for every citizen of India, including cashless in-patient and out-patient treatment for primary, secondary and tertiary care. All these services will be available to the patients absolutely free of any cost.

Under UHC all citizens of India will be free to choose between Public sector facilities and ‘contracted-in’ private providers for healthcare services.

It is envisaged that people would be free to supplement the free of cost healthcare services offered under UHC by opting to pay ‘out of pocket’ or going for private health insurance schemes

HLEG recommends ‘Price Control’ of ‘Essential Medicines’, just like draft NPPP 2011:

In its recommendation no. 3.5.1, HLEG postulated price controls and price regulation especially on essential drugs, which is quite in line with the draft National Pharmaceutical Pricing Policy 2011 (NPPP 2011). The HLEG report says:

“We recommend the use of ‘essentiality’ as a criterion and applying price controls on formulations rather than basic drugs. Direct price control applied to formulations, rather than basic drugs, is likely to minimize intra-industry distortion in transactions and prevent a substantial rise in drug prices. It may also be necessary to consider caps on trade margins to rein in drug prices while ensuring reasonable returns to manufacturers and distributors. All therapeutic products should be covered and producers should be prevented from circumventing controls by creating nonstandard combinations. This would also discourage producers from moving away from controlled to non-controlled drugs. At the same time, it is necessary to strengthen Central and State regulatory agencies to effectively perform quality and price control functions.”

Price control on essential medicines is also in force in China:

Chinese Government has put a cap on the prices of about 300 drugs featuring in their ‘National List of Essential Medicines (NLEM).’ Perhaps following the similar concept both the NLEG and NPPP 2011 have recommended price control of about 348 drugs falling under ‘The National List of Essential Medicines 2011 (NLEM 2011)’ of India.

Another recent report on ‘Free Medicines for All’:

Meanwhile,the working group of the Planning Commission on health, constituted for the 12th Five Year Plan (2012-2017) headed by the Secretary of Health and Family Welfare Mr. K. Chandramouli (now retired), has also submitted its report recently.

The Part II of the report titled, “Provisions of ’free medicines for all in public health facilities … recommends that health being a state subject, all the state governments of the country should adopt the successful and well proven Tamil Nadu model of healthcare procurement.

Tamil Nadu government through Tamil Nadu Medical Supplies Corporation (TNMSC) reportedly makes bulk purchases of drugs and pharmaceuticals directly from the manufacturers through a transparent bidding process, which reduces the cost of medicines to 1/10th and even to 1/15th of the Maximum Retail Price (MRP) of the respective product packs.

As per this report, the total running cost for the ‘Free Medicines for All’ project during the plan period would be Rs. 28,675 Crores and an additional allocation of Rs. 1293 Crores will be required as one‐time capital costs. The contribution of the Central Government at 85 % of the total cost would be around Rs 25667 crores for the entire Plan period.

Conclusion:

It was good to read that Ms. Nata Menabde, WHO country-head, India in her interview to ‘The Financial Express’ dated December 7, 2011 said, “We at WHO have been fortunate enough to be consulted on this (UHC). The meeting at planning commission was very productive and positive and we think the recommendations on the road map to Universal Health Coverage in the country is a step in the right direction.”

UHC, I reckon, will also be able to address simultaneously the critical issue of high ‘out of pocket’ healthcare expenses by the common man of the country. Implemented sooner ignoring the motivated stalling tactics, if any, by the vested interests, could usher in an era of a new healthcare reform process in the country.

That said, the proposal of the UHC in its current form does have some ‘loose knots’,which should be appropriately tightened-up through informed public discourse by the stakeholders in the healthcare space of India, sooner.

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.

From Cross-Licensing to ‘Patent Pools’ and… India: Will there be a ground swell?

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Since many years, the global pharmaceutical industry has been making effective commercial use of cross-licensing, however, by and large, the industry still does not seem to be quite in favor of  ‘Patent Pools’ for various reasons.

The ‘Patent Pool’, as I understand is defined as, “an agreement between different owners, including companies, governments and academic bodies to make available patent rights on non-exclusive basis to manufacturers and distributor of drugs against payment of royalties.”

Thus one of the often repeated key benefits of the ‘Patent Pools’, as considered by its proponents, is that the system enables the use of innovation against payment of royalties, without the risk of patent infringement. Many believe that the concept of ‘Patent Pool’ can play an immensely useful role for productive use of Intellectual Property (IP) in the global pharmaceutical industry.

The difference between cross-licensing and ‘Patent Pools’:

The basic purposes of both Cross-Licensing and patent pools may appear to be similar, however the key difference is that in ‘Patent Pool’ system the patent owners usually agree to license to third parties who may not even contribute any patents to the pool. Moreover, ‘Patent Pools’ involve a large number of parties with its scope being narrow and well standardized.

“Patent Pools”- still a contentious issue:

The concept of ‘Patent Pools’ has become a contentious issue within the global pharmaceutical industry. Some opinion leaders vehemently argue that creation of a ‘patent pool’ will bring down the cost of any innovation significantly and save huge time, ensuring speedier and improved access to such medicines to a vast majority of ailing population across the world. This section of the experts also feels, “in the case of blocking patents as a commercial strategy, it would only be a reasonable method for making the innovation publicly available.”
In the midst of this high decibel debate, on February 13, 2009, ‘The Guardian’ reported the following comment of Andrew Witty, CEO of GlaxoSmithKline (GSK) on the same issue:
“GSK will put any chemicals or processes over which it has intellectual property rights that are relevant to finding drugs for neglected diseases into a patent pool, so they can be explored by other researchers”.
Andrew Witty in that interview also commented, “I think it’s the first time anybody’s really come out and said we’re prepared to start talking to people about pooling our patents to try to facilitate innovation in areas where, so far, there hasn’t been much progress… I think the shareholders understand this and it’s my job to make sure I can explain it. I think we can. I think it’s absolutely the kind of thing large global companies need to be demonstrating, that they’ve got a more balanced view of the world than short-term returns.”
Quoting Andrew Witty, ‘The Guardian’ reported, “his stance may not win him friends in other drug companies, but he is inviting them to join him in an attempt to make a significant difference to the health of people in poor countries”.
Yet another ‘out of box’ comment:
As if to prove ‘The Guardian’ right on their above comment, during his visit to India on March 2010, though in a slightly different context, Witty made the following comments, while answering a question of “The Economic Times”:
“I am relatively relaxed with the Indian regulatory environment. The government has made it clear about the direction to have an Intellectual Property (IP) mechanism and to be TRIPS compliant. Some people are unrealistic and want everything to change overnight. But we should be absolutely realistic about pricing to keep it affordable for India. If someone has the IP right, it does not mean that it should make it inaccessible for lower income people. Over the next 10-15 years India will become increasingly IP defined market.”
The rationale for ‘Patent Pools’ system:
Many experts in this area feel that the conventional patent system does not really work for the diseases of the poor, all over the world. Though the concept of ‘Patent Pools’ is quite new in the global pharmaceutical industry, this system is being very successfully and widely practiced within the Information Technology (IT) industry. ‘Patent Pool’ system, if effectively used, as stated earlier, can also help the global pharmaceutical companies to improve access of such medicines to many more developing countries of the world.

Key requirements for the ‘Patent Pools’:
Careful identification of various patents, which will be essential for the pool, will be one of the key requirements to initiate a ‘Patent Pool’ system. It makes the need to obtain individual patents, required in the process of a drug discovery, less important.

National Institute of Health (NIH), USA initiated the process:
On September 30, 2010, NIH became the first patent-holder to share its intellectual property with the Medicines Patent Pool, supported by UNITAID, by licensing a patent for ‘Darunavir’ to increase access of HIV and AIDS medicines to the suffering patients in the developing countries of the world.

UNITAID, an innovative global health financing mechanism is funded by a levy on airline tickets. This initiative was co-founded by the U.K, France, Norway, Brazil and Chile at the United Nations General Assembly in 2006 and buys drugs against HIV/AIDS, malaria and tuberculosis.
The above move of NIH towards the noble cause was appreciated by many all over the world, urging the global pharmaceutical industry, in general, to take a leaf out of it.

India was kept out of UNITAID “Patent Pool”:

In 2009-10, UNITAID reportedly had opposed the move to include countries like, India, China and Brazil from the proposed patent pool for AIDS drugs. At least seven civil society groups from India like, the Centre for Trade and Development, the National Working Group on Patent Laws, the All India Peoples Science Network openly stated that UNITAID does not intend to share the patent pool implementation plan with these civil society groups of India. They also alleged that this development in UNITAID will have a significant impact on the ability of Indian Pharmaceutical industry to manufacture low-cost versions of patented HIV/AIDS medicines for the developing countries of the world.

At that time, it was also reported that large global pharmaceutical players had indicated to UNITAID that they could contribute to the ‘patent pool’ on a selective basis, however, over 100 middle income countries such as India, Brazil and China should not have rights to manufacture generic versions of these HIV/AIDS medicines. They felt that ‘patent pool’ will be meaningless if poor countries, who do not have the capability to manufacture these medicines, are included in the process.

However, according to UNITAID, “the patent pool in no way a means to replace or override other provisions contained in the Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement or the Doha Declaration on TRIPS and Public Health. The patent pool represents an additional tool to increase access to HIV treatment, and an opportunity for patent holders to voluntarily contribute to the attainment of crucial health-related goals endorsed by the international community.”

GSK kick-started the process:

Andrew Witty of GSK is undoubtedly the first CEO of a global pharmaceutical company to announce a ‘Patent Pool’ system for research on 16 neglected tropical diseases like, tuberculosis, malaria, filariasis, leprosy and leishmaniasis. GSK has, in a real sense, kick started the process by putting more than 500 granted pharmaceuticals patents and over 300 pending applications in the ‘Patent Pool’.

J&J followed suit:

Johnson and Johnson (J&J) in January 2011 expressed its willingness to assist ‘Medicines Patent Pool Foundation (MPPF)’ to implement ‘Medicines Patent Pool (MPP)’, which aims to improve access to affordable and appropriate HIV medicines in developing countries. MPPF works through voluntary licensing of patents for public health interest, at the same time extending compensation to the innovator pharmaceutical companies.

‘Medicines Patent Pools’:

On April 7, 2011. ‘Intellectual Property Watch’ reported that the ‘Medicines Patent Pools’, an initiative to improve access to HIV drugs through voluntary licenses of patented drugs, have launched a new database of patent information on HIV medicines in developing countries. The database has been developed with the support of the World Intellectual Property Organization (WIPO) and Regional Patent Offices across the world. Intellectual Property Watch

Key issues with the ‘Patent Pools’ concept:
The report from a WHO conference held in April, 2006 ‘Innovation Strategy Today’ indicates that the start-up cost of a ‘Patent Pools’ for vaccines will be economically viable only if more than 25 participants holding relevant patents join the initiative.
Moreover, various types of litigation related to patents, which are being currently witnessed within the global pharmaceutical industry, could also be an impediment in getting more patents in the pool.

Recommended ‘General Principles’ for “Patent Pools”:
International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), Switzerland, suggested the following guidelines for the ‘Patent Pool’ initiatives:
1. Patent pools should be voluntary associations of entities formed without coercion 2. Objectives of any patent pool should be clearly defined 3. Patent pools should complement rather than replace elements of existing intellectual property regimes 4. Rights and obligations of contributors and licensees of contributed rights should be clear 5. Patent pools should reduce transaction costs, and not increase administrative costs, relative to other options such as direct licensing
Conclusion:
There is certainly an urgent need to communicate more on how innovation and IPR could help rather than hinder public health. At the same time all stakeholders of the pharmaceutical industry need to come out with a robust solution to ever increasing problem of improving access to innovative medicines to the ailing population of the world, in the best possible way.
However, these are still very early days, before such a disrupting idea get widely accepted by the global innovators and implemented religiously not just for the ‘public health interest’, across the world, but also to create a sustainable business model to harvest ‘Fortune at the Bottom of the Pyramid’.

Only future will tell us whether or not the ‘Patent Pools’ initiatives become the footprints on the sands of time as the global pharmaceutical industry keeps  navigating through the challenges of change.

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.

Biologic Medicine: Ushers in a different ‘Mega Race’ for inorganic growth

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During the last several years the success of biologics compared to conventional small-molecule drugs to meet the unmet needs of patients, is gradually but surely changing the area of focus of pharmaceutical R&D altogether, making the biotech companies interesting targets for M&A. Over a period of so many years, the small-molecule blockbuster drugs business model made pharmaceuticals a high-margin industry. However, it now appears that the low hanging fruits to make blockbuster drugs have mostly been plucked.

These low hanging fruits involved therapy areas like, anti-ulcerants, anti-lipids, anti-diabetics, cardiovascular, anti-psychotic etc. and their many variants, which were relatively easy R&D targets to manage chronic ailments. Hereafter, the chances of successfully developing drugs for cure of these chronic ailments, with value addition, would indeed be a very tough call.

Deploying expensive resources towards finding a cure for so called ‘chronic diseases’ may also not promise a strong commercial incentive, as the treatment for ulcer, lipid disorders, diabetics, hypertension etc. are currently continues lifelong for a patient and a cure will limit the treatment to a short to medium term period.

Greater promise in biologics:

On the other hand, the bottom-line impact of a successful R&D outcome with safer and effective drugs 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, Alzheimer’s diseases etc., will be huge. It is believed that well targeted drugs of biologic origin could well be successful treatment for such intractable diseases.

The golden opportunity of meeting the unmet needs of the patients with effective biologics, especially in high-growth therapeutics, as mentioned above, has given the M&A activities in the pharma-biotech space an unprecedented thrust.

Biologic versus conventional drugs:

Biologics Conventional and NME drugs
Large molecules (>5000 molecular weight) Small molecules (~500 molecular weight)
Bio-technologically produced or isolated from living sources Chemically synthesized
Complex structure/mixtures (tertiary structure, glycosylated) Simple well-defined structure
High target specificity Less target specificity
Generally parenteral administration (e.g., intravenous) Oral administration possible (pills)

(Source: MoneyTreeTM Report. PWC, 2009)

According to IMS, Biologics contribute around 17% of global pharmaceutical sales and generated a revenue of US$120 billion MAT March 2009. As we see today, gradually more and more global pharmaceutical companies, who used to spend around 15% to 20% of their annual sales in R&D, are channelizing a large part of the same to effectively compete in a fast evolving market of biologics through mainly M&A route. This is also driven by their strategic intent to make good the loss in income from the blockbuster drugs going off patent and at the same time fast dwindling R&D pipeline.

A shift from small molecule based blockbuster model to a biologics-based blockbuster one:

Frost & Sullivan forecasts a shift from small molecules-based blockbuster model to a biologics-based blockbuster one for the global pharmaceutical majors, just as biologics like Enbrel ,Remicade, Avastin, Rituxan and Humira, as mentioned below, have already proved to be money spinners.

The top 10 global brands in 2009:

Rank Product Chemical/Biologic Global Sales US$ Mn
1 Lipitior Chemical 12,511
2 Plavix Chemical 9,492
3. Seretide/Advair Chemical 7,791
4. Enbrel Biologic 6,295
5. Diovan Chemical 6,013
6. Remicade Biologic 5,924
7. Avastin Biologic 5,744
8. Rituxan Biologic 5,620
9. Humira Biologic 5,559
10. Seroquel Chemical 5,121

(Source: EvaluatePharma)

Faster growth of biologics attracting attention of large pharma players:

Currently, faster growth of biologics as compared to conventional new chemical entities is driven by novel technologies and highly targeted approach, the final outcome of which is being more widely accepted by both physicians and patients. The large global pharmaceutical companies are realizing it pretty fast. The type and quality of their recent acquisitions, vindicate this point.

Mega race for biologics and vaccines:

Driven by the above factor, in 2009 Pfizer acquired Wyeth for US $68 billion, Roche acquired Genentech for US $ 47 billion and Merck acquired Schering-Plough for US $ 41 billion. Only the above three M&A are valued more than US $ 150 billion and that too at a time of global financial meltdown.

Acquisition of Wyeth enabled Pfizer to expand its product-mix with vaccines, animal health and consumer products businesses and at the same time leveraging from Wyeth’s biologics capability.

Similarly, Merck got tempted to acquire Schering-Plough mainly because of latter’s rich R&D pipeline with biologics.

Roche, which was basically a pharmaceutical company, post-acquisition of Genentech, became a major bio-pharmaceutical company with a great promise to deliver in the years ahead.

Other M&As, which would signify a shift toward the growing space for biologics are the acquisition of MedImmune by AstraZeneca and Insmed by Merck and the recent bid of Sanofi-Aventis for Genzyme.

Faster growth of biologics:

As mentioned above, despite patent cliff, biologics continue to contribute better than small molecules to overall growth of the R&D based global pharmaceutical industry.  Most of these biologics are sourced either through acquisition or  collaborative arrangements.

Currently cash strapped biotech companies with molecules ready for human clinical trials or with target molecules in the well sought after growth areas like, monoclonal antibodies, vaccines, cell or gene therapies, therapeutic protein hormones, cytokines and tissue growth factors, etc. are becoming attractive acquisition targets, mainly by large pure pharmaceutical companies with deep pockets.

Another M&A model:

Besides mega race for mega acquisitions, on the other hand, 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 diseases. In 2009 the same Gilead acquired CV Therapeutics for US $1.4billion to build a portfolio for cardiovascular drugs.

Smaller biotech companies, because of their current size do not get engaged in  very large deals, unlike the top pharma players, but make quick, decisive and usually successful deals.

Another commercial advantage for biologics – lesser generic competition :

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

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

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

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

Change of appetite:

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

Conclusion:

Although the large pharma majors are experimenting with pure biotech companies in terms of acquisitions and alliances, it will be interesting to see the long term ‘DNA Compatibility’ between these companies’ business models, organization and work/employee culture and market outlook to improve their overall global business performance, 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-aventis at a later date, helps synergizing the overall R&D productivity of the merged companies.

In this context, Frost & Sullivan had commented: “Widely differing cultures at Roche and Genentech could make retaining top scientists a huge challenge. Roche is Swiss and a stickler for precision and time, while Genentech has a more ‘Californian attitude’ and is laid back and efficient in its work”.

Though the long-term overall financial impact of the ‘mega race for mega deals’, as mentioned above, is less clear to me, acquisition of biotech companies, especially well thought through smaller ones, seems to be a pretty smart move towards inorganic growth by the global innovator companies.

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.