IPR and Medicines 28: Politicizing Innovation, Rewarding Rent-Seeking

Indian government's intellectual property rights (IPR) system for medicines seems hazy. For instance, it did not give full patent protection for medicines before, until India joined the WTO in 2005. Even then, many innovator drugs have no IPR protection, like the case of popular anti-leukemia drug molecule imatinib, brand "Glivec" or "Gleevec" made by Novartis.

According to wikipedia, anti-chronic myelogenous leukemia (CML) drug imatinib, "more than 90% of patients will be able to keep the disease in check for at least five years, so that CML becomes a chronic, manageable condition."

So Novartis in effect is sort of a "hero" to many leukemia patients for coming up with this revolutionary drug. But many sectors in India (and elsewhere around the world) did not look at it this way. Rather, Novartis is looked upon as a blood-sucking multinational who profits from the sick and dying leukemia patients. Thus, its effort to seek IPR protection through a patent was not recognized by an Intellectual Property agency or office in India. So it went to the Indian Supreme Court to obtain such patent and after about a decade of legal and health debates, the SC has ruled against the company's request.

From wikipedia article about leukemia, there are four kinds of this disease. Their respective medication are as follows (image also from wiki):

(1) Acute lymphoblasticinduction chemotherapy.... For adults,... prednisone, vincristine, and an anthracycline ....L-asparaginase or cyclophosphamide. For children... (prednisone, L-asparaginase, and vincristine)Consolidation therapy or intensification therapy ...  antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP) 

(2) Chronic lymphocyticcombination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroidsuch as prednisone or prednisolone....  fludarabine, pentostatin, or cladribine.... Younger patients may consider allogeneic or autologous bone marrow transplantation.

(3) Acute myelogenousMany different anti-cancer drugs are effective for the treatment of AML

(4) Chronic myelogenousstandard of care is imatinib (Gleevec) therapy

For Hairy cell leukemia,  . cladribine, ...  pentostatin... , rituximab ... Interferon-alpha. And for T-cell prolymphocytic...  purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone CHOP, cyclophosphamide, vincristine, prednisone [COP], vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin VAPEC-B). Alemtuzumab...

So there are many existing drugs against leukemia, depending on the cell type and on whether it is acute or chronic. So they are all non-patented or off-patent already in India?

Novartis and other innovator companies are brave to introduce their new and more revolutionary medicines to Indian patients without IPR protection. Or if they have have one, they have to live with the fact that a patent-confiscation government tool called compulsory licensing (CL) can be imposed by the Indian government anytime.

One result of this situation is an uneven competition. An innovator company that spent huge amount of money and many years in R&D and multiple clinical trials, must sell at a high price to recoup its high spending. Then generic producers that spent nothing to discover the original drug molecule but can produce their own brands of the same molecule can sell at a much lower price.

How can the former adjust with this reality? Plain old economic sense would dictate market segmentation -- different (or tiered) pricing for different buyers or patients with different budget. And for really poor patients, zero cost to them via public-private partnerships or via civil society partnerships. I am told by a friend that Novartis in India has various drug donation programs, like partnership with the Max Foundation, a cancer patient advocacy organization, and gave the Glivec International Patient Assistance Program (GIPAP) providing more than US$ 1.7 billion worth of Glivec to poor patients in India. In effect, the company was giving not cheap but free medicines to the poor, funded by high pricing to richer patients who can afford it.

I also read this interesting article, and I like the first of six "side effects" of the Glivec ruling in India: Patenting is a political act. It is not a scientific or economic act. One must go through strictly political process to obtain a patent. Or if one has it, go through the same political process to retain and protect it, until the patent has  expired. The author, William Looney, wrote,

what constitutes true innovation in an age where scientific advances are transforming the very definition of a drug?  This is a question that extends far beyond patent law into basic value judgments like how society should spend limited resources on medical technologies, in a way that balances patient access with the economic incentives needed to seed their development in the first place.  

It is not good to politicize innovation. There is too much politics in our lives already. Wages, fares, prices of certain commodities, setting up a business, closing a business, hiring and firing workers and managers, they are covered by politics. To extend politics to products of scientific discovery, when none of the money spent for such activity came from taxes, is OA.  

The climate for IPR in India has become more uncertain. Last year, the Indian government issued their first compulsory license, which permits local companies to make generic copies of a patented medicine for a small fee. Since January 2013, three additional compulsory licenses were issued for three different cancer drugs.

As more politics raid products of innovation, more rent seeking behavior is rewarded. This is not the proper role of government, to pick winners and losers based on certain subjective if not arbitrary criteria. The proper role of the government in this case, is to leave players to do their own thing so long as public health is not endangered. So if there are 30 or 50 innovator companies who would race with each other in producing a new medicine against prostate cancer or breast cancer or other killer diseases, so be it. These are on top of existing drugs and treatment against those diseases that are off-patent already. Let those innovator companies price their own products. For sure, competition among them will force them to develop various types of pricing and drug donation programs.

Less politics, less government intervention in the drug innovation business and competition. This is one cool way to ensure that present and future patients suffering from killer diseases can find solace and hope to lengthen their lives.

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See also:
IPR and Medicines 24: Balancing Costly Innovation and Cheaper Drugs, March 20, 2012
PR and Medicines 25: Patents, Diagnostics and Technology Transfer, October 02, 2012
IPR and Medicines 26: Novartis' Glivec and India's IPR Ruling, April 01, 2013, 
IPR and Medicines 27: More on Glivec and India's SC Decision, 

IPR and Medicines 27: More on Glivec and India's SC Decision

A friend in our local health coalition, CHAT, commented in my earlier article, Novartis' Glivec and India's IPR Ruling and argued that

(A) medicine to be patentable should be NEW. This in essence only disallows evergreening of patents which seems to be what Novartis tried in the India case. And which most super power countries like the US and EU where most MNCs are from, would like to change through the insertion of TRIPs plus provisions in bilateral FTAs.  

Precisely why the TRIPs flexibilites are in place is to promote the primacy of public health and ensure that developing and undeveloped countries like ours and India (I presume) can have greater access to medicines. 

A friend from the innovator pharma camp told me today that

What does not get written about is that Novartis provided 95% of all originator Glivec for free to those patients who had been prescribed the medication in India! The remaining 5% were reimbursed, insured or participated in a generous co-pay program. Facts like these just don't get the media mileage.

The New York Times continue with its gloating and implicit celebration of the India Supreme Court ruling, with news today like Health Care Advocates Cheer Supreme Court Decision, saying,

...The case represents a high-stakes showdown between defenders of intellectual property rights, who say generic versions stifle innovation by drug makers, and Indian drug companies and international aid groups, who warned that a ruling in favor of Novartis could have dried up the global supply of inexpensive medicines to treat AIDS, cancer and other diseases.

Huh? IPR advocates (me included) say that "generic version stifle innovation"? Where did they get that? ALL patented drugs will become off patent after sometime, and generic versions come in, and this has little or zero effect on promoting or stifling drug innovation. What stifles innovation is the uncertainty of patent confiscation by the government. An IPR for an innovator company in the form of drug patent (or song or book copyright or company trademark and logo) can be confiscated through compulsory licensing (CL) and the use of a new, commercial molecule will be given to somebody else, say a government pharma corporation or a private crony corporation.

Anyway, there is an interesting article that I saw today, 

Novartis Loses The Glivec Patent Fight In India, 

http://seekingalpha.com/article/1313001-novartis-loses-the-glivec-patent-fight-in-india?source=email_rt_article_readmore

The author, Derek Lowe, wrote:

Novartis (NVS) has never had a patent for imatinib (Glivec/Gleevec) in India. I'm not completely sure why that is, but I would think it's because that back when the compound was being developed was the era when Indian drug patents did not exist. As the country has entered the WTO, it has had to comply with the world's intellectual property framework and it's safe to say that the dust has not yet settled from this process. 

So when Novartis filed for an imatinib patent in India, it was for a different polymorph of the drug, which it ihoped would be patentable chemical matter. The Indian patent office disagreed in 2006, saying that this was merely a reformulation of an existing compound (which had been approved in the U.S. in 2001), and rejected the application. Novartis has been appealing that decision through the Indian court system ever since, and this latest ruling is the last from the Indian Supreme Court. As the court's decision says: 

In the application it claimed that the invented product, the beta crystal form of Imatinib Mesylate, has (i) more beneficial flow properties: (ii) better thermodynamic stability; and (iii) lower hygroscopicity than the alpha crystal form of Imatinib Mesylate. It further claimed that the aforesaid properties makes the invented product 'new' (and superior!) as it 'stores better and is easier to process'; has 'better processability of themethanesulfonic acid addition salt of a compound of formula I'; and has a 'further advantage for processing and storing.'

Here is Novartis' take:

Glivec has been awarded patents in nearly 40 other countries, including China, Russia and Taiwan, but the IPAB is denying one for India. The IPAB acknowledges that Glivec satisfies the international requirements for novelty and inventiveness, but it does not find Glivec to meet the requirement under Section 3(d) of the Indian Patents Act of 2005. This act introduced a new efficacy enhancement hurdle for patenting new forms of known compounds. We believe that Section 3(d), the Indian legal paragraph intended as a hurdle for evergreening, should not be applicable to the breakthrough medicine Glivec, which has changed the lives of patients with rare cancers.

I like the author's concluding statements:

...(I might note that all the preening in the Indian press about the country being the "pharmacy to the world" would be more justified if any of the drugs being made had actually been discovered in India, through the ingenuity of Indian drug companies, risking Indian capital and shareholders' money. But they weren't.) What it does mean is that Indian drug patent law has gone from being nonexistent a few years ago, to being one of the strictest around. I hope that it's applied uniformly. Novartis has lost what was not a very strong case, to be honest, but the courts in India will hear stronger at some point.

So to my friend's query if Glivec in beta-crystalline form was a novel drug or not, the nearly 40 countries where it got a patent said Yes, it is a novel drug, that is why a patent was granted in those countries.

What is clear to me at this point are the following:

1. Glivec/Gleevec was a real, revolutionary, cancer-killer medicine. Physicians and patients were looking for it. Kudos to Novartis -- and not to anyone else -- for inventing it, for spending a billion dollars (industry average) in medicine R&D.

2. Because of this usefulness and revolutionary-ness of Glivec, many generic manufacturers in India salivated at the profitability of copying it even if they did not spend a single dollar in various clinical trials involving hundreds or even thousands of cancer patients. Since they did not spend any to invent this revolutionary drug, they can copy and sell it even at 10 percent or four percent of the innovator's price and still make a good profit.

3. This case does not seem to fall under the TRIPS flexibilities of WTO because there was no patent to null in the first place. There was no need to issue a compulsory licensing (CL), a tool in the TRIPS flexibilities and also in our RA 9502 (Cheaper Medicines Law of 2008), because there was no patent to start with. 

One implication of this case is that innovator companies -- of which there is few (or zero?) in India -- will have second thoughts whether to bring to India new, more disease killer medicines, or not. Or delay launching it there when the patent elsewhere is about to expire. In which case, patients will have to use old and existing, off-patent drugs. If they wish to get those more powerful drugs, they may have to fly to the US or Europe or Japan or HK, etc. and seek treatment there. And this makes healthcare becomes even more expensive.

Lest I will be accused of being "unsympathetic" or "antagonistic" to generic pharma, I am not. Generic producers have a role to play in public healthcare. After the patent of a popular and revolutionary medicine has expired, generics come in and provide their own versions at a lower price to the public. In the WHO's Essentials Medicines List, I read that about 99 percent of those medicines are off-patent and are available at various brands at various low prices. Thanks to generic pharma.

It is only in that short "patented period", usually only 8-10 years of the total 20-years patent life of a drug molecule (the 10-12 years are eaten by various clinical trials and approval process by the FDA) that is being debated.

Because of the important and useful role of innovator pharma companies in discovering new more powerful, more disease-killer medicines, certain government policies should not be antagonistic to them. Instead of just 100 or so innovator companies worldwide, we should have 300 or 1,000 of them worldwide. Let there be more competition among innovator companies, the same way that we wish to see more competition among generic companies. Competition and not more government regulation, is almost always a more effective tool to bring down prices.

Abolition or at least drastic reduction, of government taxes on medicines, will be a good start. This move will drastically reduce medicine prices and hence, address public clamor for cheaper medicines.

For a full copy, 112-pages long, India Supreme Court decision, see here,
http://www.scribd.com/doc/133343411/Novartis-patent-Judgement
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See also:
IPR and Medicines 23: Profitability of Innovator Pharma Companies, March 16, 2012
IPR and Medicines 24: Balancing Costly Innovation and Cheaper Drugs, March 20, 2012
PR and Medicines 25: Patents, Diagnostics and Technology Transfer, October 02, 2012
IPR and Medicines 26: Novartis' Glivec and India's IPR Ruling, April 01, 2013

IPR and Medicines 26: Novartis' Glivec and India's IPR Ruling

A very good friend of mine here in Manila has a brother with leukemia. His physician recommended Gleevec or Glivec (generic molecule is "Imatinib") made by Novartis, as the medicine that can help him beat the disease. The problem was that Gleevec was very expensive, so the family approached a foundation. The foundation conducted a credit investigation re the financial capacity of the patient's family and determine how much free medicines they can get. The investigation agency suggested a "Plan 9", meaning Novartis through a foundation will give them nine months worth of medicines for free, but the family must buy the first three months supply of Glivec. This was sometime in September 2011.

A capsule of Glivec (photo here from wikipedia) then would cost P1,204.00, the 12 percent VAT + import tax + other taxes and fees included. The patient would need six boxes (60 capsules per box) or 360 capsules for three months, that would cost them P433,440, but the supply for the next nine months would be given free by Novartis.

The family looked for other options. One was to buy the medicine not from the Novartis med rep at the private hospital where the patient goes, but from the company med rep at the Philippine General Hospital (PGH). Second option was to buy from India or elsewhere, and after several emails with their friends in Delhi, they found that a generic alternative, Imatinib Mesylate, is available in India at a much lower price. 

There's a special case in India about Imatinib or Gleevec. The Indian High Court rejected the patent application of Novartis. So while Gleevec is patented in many countries, it was not in India. So many generic manufacturers produced their own versions of imatinib. And since they spent nothing on the long process of various clinical trials and medicine R&D that takes up to 12 years sometimes, they simply copied it from Novartis, they could sell the medicine at a much lower price. One Indian manufacturer could sell it at only about four percent of the original price of Novartis, exclusive of Philippine taxes like VAT.

Today, I read this news report from the NYT:

Top Court in India Rejects Novartis Drug PatentBy GARDINER HARRISPublished: April 1, 2013 

NEW DELHI — India’s Supreme Court rejected a Swiss drug maker’s patent application for a major cancer drug Monday in a landmark ruling that allows cheap copies of important medicines to continue being distributed in much of the world. 

The ruling allows Indian generic companies to continue making copycat versions of the Novartis drug Gleevec, which can have a miraculous effect on some forms of leukemia.

But the ruling’s effect will be felt well beyond the limited number of patients in India who need Gleevec because it will help maintain India’s role as the world’s most important provider of cheap medicines, which is critical in the global fight against HIV/AIDS and other diseases.

Novartis had hoped that India’s adoption under international pressure of a new patent law would lead the country to grant the company an exclusive license to produce Gleevec, which can cost up $70,000 per year. Indian generic versions cost about $2,500 year....

In recent decades, the United States has become increasingly insistent that countries wishing to do business there adopt far more stringent patent protection rules, with the result that poorer patients often lose access to cheap generic copies of medicines when their governments undertake trade agreements with the United States. 

The ruling Monday is bound to be seen with some concern by the United States and the international pharmaceutical industry and may be yet another blow to India’s standing among major multinational companies, many of whom view protection of their intellectual property as vital to their business interests.