Neither the long-term health of their clientele, nor the affordability or true effectiveness of a drug matches profit-making as a motivator for drug companies.
Although nations frequently clash over intellectual property rights, at the individual level nothing drives home the practical implications patent systems abuse like the manipulation drug production by some companies, which directly affects one’s own health or the health of a friend or family member.
A close friend was recently at the receiving end of what appears to be deliberate malfeasance within the U.S. drug patents system, and the facts of his case supply context to the battles that have played out over the last few years in the India-U.S. bilateral space.
Notwithstanding steady progress in other areas of bilateral cooperation such as defence, the sphere of intellectual property rights has become a veritable minefield for the India-U.S. relations.
Although disputes have existed for years now, notably including the Basmati-Jasmati-Texmati brouhaha of the late 1990s, recent landmark decisions by the Supreme Court of India rejecting drug patent applications made by major foreign pharmaceutical companies have stirred the pot again.
In turn, this has raised deep questions about the rules of the game.
One relevant ruling by the highest court in the land came in April in response to an application by Swiss drug maker Novartis, which sought patent protection for its cancer drug Glivec.
The Indian Supreme Court refused grant a patent for the drug arguing that the drug was merely an extension of existing medications, not a ground-breaking advancement. This is also known in the industry as “ever-greening,” for obvious reasons.
Although the Court’s ruling raised a cacophony of partisan voices in the West, fearful that India’s commitment to affordable generics for life-saving drugs could hit their bottom line, Indian officials patiently went about explaining the Supreme Court’s decision and why India had not flouted international patent laws enshrined in the Trade Related Intellectual Property Rights agreement of the World Trade Organisation.
For example India’s Ambassador to the U.S. argued in The Hill’s Congress blog that during 2005-11 more than 4,000 patents for pharmaceutical inventions were issued by the Indian Patent Office and among those “20-30 per cent were awarded to U.S.-based companies each year, and more than 85 per cent were owned by foreign companies in India.”
Ms. Rao went on to note, “Compulsory licensing has been an integral part of the patent regime of many countries for years. Fifteen countries, both developed and developing countries alike, have issued more than 35 compulsory licences.”
In another well-argued article Shamnad Basheer pointed out in The Hindu that the U.S. “routinely issues such licences… through their courts which refuse to grant patent injunctions on grounds of public interest,” and thus it forces foreign drug manufacturers to drop their drug prices.
When my friend faced four months of deterioration in his health directly owing to certain actions taken by a U.S. manufacturer, it became all too apparent to me that it is not only foreign drug companies – for example Indian manufacturers of generics – that are under pressure from large Western pharmaceuticals; but even patients in the U.S. can be left suffering if a drug manufacturer ceases to make profits off a particular patent.
Here are some details from his case.
A few years back my friend was diagnosed with an inflammatory bowel condition. This was treated with an anti-inflammatory drug called mesalamine, which in the U.S. is manufactured by a drug company called Warner-Chilcott, under the name Asacol 400mg (as it contained 400mg of mesalamine per tablet).
His treatment with this drug had been proceeding according to plan until March this year, when, suddenly, his gastroenterologist informed him that Warner-Chilcott had stopped further production of the drug, apparently because it had been discovered that there was an ingredient used in its enteric coating that might be harmful to human beings. The name of this ingredient is Dibutyl Phthalate (DBP)
While he was disappointed – Asacol had worked for him better than any other drug he had tried until then – he switched immediately to another mesalamine-based drug made by Warner-Chilcott. The company said that this substitute, a drug called Delzicol, did not have DBP.
Delzicol failed miserably. His condition flared up again and for four months he continued to deal with a host of familiar but unpleasant symptoms. When he went back to his doctor he was told, “A lot of patients came back saying that Delzicol did not work as well as Asacol did,” despite Warner-Chilcott’s assurances that it was the bio-equivalent of Asacol.
He was then switched to another, older, mesalamine variant called Lialda, but that too did not produce the sort of stability in his condition that Asacol did. In a stroke of luck, however, he was able to obtain Asacol 400mg from India – where it was being imported from a Swiss manufacturer – and there was clearly no issue there with DBP. Something did not add up.
Although his condition has steadily improved again since he returned to Asacol 400mg, a few troubling questions remained regarding Warner-Chilcott’s actions. In addition to Delzicol the company makes a second mesalamine variant, Asacol HD. Despite Asacol HD containing DBP as Asacol 400mg did, it is still on the market. Why?
Coincidence or standard “out-patent” procedure?
I was intrigued by this case and wanted to help my friend look into it further. I spoke to several gastroenterologists about Asacol 400mg’s discontinuation and soon discovered that on July 30 2013 the patent that Warner-Chilcott had for Asacol 400mg had expired. Was it pure coincidence that they “discovered” the problem of DBP a few months before the drug went off patent and then recommended that patients switch over to another Warner-Chilcott product?
The pieces of the puzzle seemed to be falling into place – now the continuation of Asacol HD on the market despite it containing DBP made sense, as Asacol HD is still protected by a patent. It also turns out that Asacol HD has significantly higher co-pays under many health insurance plans, which means more money in Warner-Chilcott’s pockets.
One factor that appeared to have been a pure coincidence was the U.S. drug regulator, the Food and Drug Administration, issuing a guidance note on DBP, however one that neither mentioned Warner-Chilcott nor Asacol 400mg. This seemed to have neatly played into the hands of Warner-Chilcott, who then had the perfect excuse for dropping expiring-patent Asacol 400mg from production while continuing to produce patent-protected Asacol HD (and anecdotally ineffective Delzicol).
Uphill struggle for generics
The obvious question that this sorry tale of gaming the system begs is why no generic mesalamine drugs have entered the market yet. In fact in the U.S. the usual arch-villains of the healthcare industry, insurance companies, are actually the “good guys” in this case and a strong force pressing for the development of generics, even if they do so with the aim of boosting their own profits.
Yet, according to patent attorney Gideon Eckhouse, there are many other mesalamine patents out there that could prove to be roadblocks to generic production of Asacol 400mg, not least because many of the components of Asacol 400mg and Asacol HD are similar to each other.
That generic substitutes for Asacol 400mg have not emerged in the U.S. is also a testament to certain quirks of the patent landscape in this country.
A patent can be invalidated if it can be shown that “prior art” – which refers to information made publicly available before a given date that is relevant to a patent's claims of originality – existed before the date on which the patent holder filed the patent application or the date on which the inventor claims they invented the product or service. Patents may also be invalidated on the grounds of other, procedural and regulatory, reasons for failing to comply with the Patent Office’s requirement. In the case of Warner-Chilcott’s active patent, the one for Asacol HD, they assert an inventive date of November 20, 2000.
In addition to invalidating a patent with prior art before this date, Mr. Eckhouse explained, generics companies may comply with FDA requirements and bring their product to market by asserting that their generic equivalent is not encompassed by the scope of Warner’s patent.
It appears there may be hope for generic challengers of the patent in this regard, as some have argued that there may be nothing in the Asacol HD patent that is specific to its 800mg dose. Instead that patent is based entirely on the coding of the polymers in the drug, which help to delay the release of the active ingredient for absorption in the gut.
Generics manufacturers of drugs seeking to replace the expired-patent Asacol 400mg, on the other hand, would benefit from another U.S. law dating back to 1984, the so-called Hatch-Waxman Act. Under the Act, which aims to make it easier for generic drugs to hit the U.S. market, the manufacturers of these drugs would need to prove their product’s bioequivalence to the original branded drug to win FDA approval and certify noninfringement or invalidity of Warner’s patent.
However until such manufacturers come forward with patent challenges or new drug proposals, get into litigation with Warner-Chilcott and work it out in court, it will be patients like my friend who pay a very real price for rampant ever-greening that goes on in the name of patent law in this country.
At least he had the option of getting Asacol 400mg from India, unlike thousands of other Americans suffering from similar conditions who have been left high and dry.