The combination drugs debate: unstable and unpatentable - Pharmaceutical Technology

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The combination drugs debate: unstable and unpatentable


Pharmaceutical Technology Europe
Volume 21, Issue 9

For an alternative view on combination drugs, go to http://www.pharmtech.com/overcome


(David Gould/Getty Images)
Combination products have been researched and administered for many years, some successfully and others not. I believe that the combination of several active ingredients into one pill, whilst providing a more efficacious remedy, comes with its own set of risks, largely relating to stability. Regulatory and patent challenges also exist when considering the combination of approved and off patent ingredients. In this article, I will specifically discuss one case of a combination product — the polypill; a therapeutic that combines either five or six active ingredients, which was proposed some 6 years ago as a cardiovascular disease preventative.

The idea of a combination therapeutic is not so new. During the 16th Century the notion was already the subject of much amusement:

"I was in the company where one, I know not who, of my fraternity brought us intelligence of a new sort of pill made up of a hundred and odd ingredients: it made us very merry, and was a singular consolation, for what rock could withstand so great a battery." Michel de Montaigne, French essayist (1533–1592).

What is the polypill?

Polypill, a name that was coined by consumer press, has attracted much media attention in recent months, largely because it has been hyped as a miracle drug for the prevention of heart attacks. Proposed in 2003 by Ward & Law in the British Medical Journal (BMJ), the putative polypill contains a statin, an angiotensin converting enzyme (ACE) inhibitor, a beta blocker, a diuretic, aspirin and folic acid.1

In the same issue, BMJ's Editor wrote an opinion piece titled, "The most important BMJ for 50 years " This attracted considerable attention in 2003 and 2004, but almost zero activity beyond claims that it would reduce cardiovascular disease by 80%. Later that year, the Editor of BMJ suggested that the polypill would be available in 2 years.2 This was somewhat optimistic, particularly in light of an article published in UK newspaper The Independent (7 July 2003) titled, "The one problem with the polypill is that it doesn't exist", in which it was revealed that Professor Ward had tried to interest drug companies and various medical organizations with no success, because such a product would not be patentable.

Combination controversy

In support of The Independent's view, various authorities have further dampened enthusiasm, claiming that commercial considerations stand in the way of the "discovery" being introduced overnight; with all ingredients being off patent, companies might be deterred from investing in development work. Conversely, it has been claimed that the cost to manufacture this pill may only be a few pence, which surely contradicts any commercial arguments.3

Much of the controversy surrounding this therapy, however, has revolved around various medical claims and counterclaims regarding the nature of the clinical trials that are required to prove this treatment's efficacy. Most recently, The Indian Polycap Study (TIPS),4 which tested the efficacy of the agent in healthy adults, was criticized because it simply measured the lowering of blood pressure and high density lipoprotein (HDL). This was no great revelation given that these are the prime actions of the individual ingredients.


The author says...
Setting aside the medical controversy (which often seems to rely on intuition or meta-analysis rather than hard data), some significant points have been ignored in the recent debate.

The 2009 version of the original polypill4 is minus an ingredient — folic acid. However, given the conclusions of a recent Lancet study indicating that low dose aspirin should not be used in prophylaxis for patients who have not had a heart attack or stroke,5 one might ask the question: should aspirin also be dropped?

There are, however, some fundamental problems regarding the chemistry and formulation of the polypill as it is currently proposed.


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