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Wednesday, 1 September 2010

Evergreen or nevergreen: that is the question

Guy Selby-Lowndes is the IPKat's friend -- and one of his oldest readers in both senses of the word. A greatly experienced patent attorney, he also possesses a curiosity and liveliness of intellect that this Kat very much respects. Guy has written to the IPKat as follows:

"The daily tablets I consume purportedly produce favourable effects within my body but two of them also exercise my mind; perindopril and valsartan.

The product called generically PERINDOPRIL was for some years protected by a patent owned by Les Laboratoires Servier (LLS). While they had the patent monopoly they sold the product as the tert-butylamine salt [also referred to as the erbumine salt] using the trade mark COVERSYL. After litigation around the world it was established, at least in the UK, that the patent coverage had ceased [see earlier IPKat posts here and here and PatLit here]. LLS continue to market PERINDOPRIL as the tert-butylamine salt but under its generic name only. However they have obtained European patent 1 354 873 for the arginine salt of perindopril. They are now using the COVERSYL trade mark on this product which has potential patent protection until at least 2023. The European patent is currently in force in the UK. The change evergreens the COVERSYL trade mark.

Work carried out by the Australian government has concluded that there is no clinical advantage in prescribing the arginine salt rather that the tert-butylamine salt. The alleged improvement in using the different salt relates to storage under extreme conditions. However there is a cost difference. The BNF price for a packet of 30 PERINDOPRIL tert-butylamine 4 mg tablets is £2.74 whereas the cost for the equivalent arginine salt is £10.22 [Due to molecular weight differences the equivalent arginine salt tablets are 5 mg.] The price differential follows all sizes of tablets.

Doctors are not adept at noticing things like patent expiries and frequently prescribe by trade mark name rather than generic name. If COVERSYL tablets are prescribed it is likely that most pharmacists will dispense the more expensive perindopril arginine salt at a higher cost but of no higher benefit to the patient. In Australia their robust system has insisted the two salts of perindopril are sold at the same price!

Doctors' adhesion to trade marks is exemplified by the fact that many advise PANADOL for headaches and other minor afflictions. The relevant patent has long expired and generic paracetamol is widely widely available and costs less. However the word of a doctor is so revered by many that they insist on purchasing PANADOL rather that the less expensive equivalent.

Valsartan, marketed in the UK as DIOVAN, has not featured in any of your blogs so far. Its SPC expires next year and there has already been a spat in the US between the patentee and an Indian generic manufacturer".
Says the IPKat, this is a provocative little piece: I can almost hear the hiss of steam billowing out of some readers' ears as they seethe with indignation at these attempts to preserve protection beyond what might be regarded as its reasonable limits. Well, says Merpel, I expect that other readers will be nodding vigorously with approval at the fact that some well-run and highly focused companies have sought, within the limits of the law, to maximise the value of their investments in a market which is increasingly competitive and dominated by manufacturers of sure-profit generic products.

Evergreening here (per Wikipedia) and here (per European Generic Medicines Association)
How to play the Evergreen Game here

6 comments:

Dr Mark Summerfield said...

I cannot let the Australian reference pass without comment!

There has been no "work carried out by the Australian government". In fact, the bioequivalency of the erbumine and argenine salts was demonstrated by LLS itself, which facilitated the approval and listing of the new formulation for use in Australia.

The prices are the same again because of voluntary action by LLS. Had LLS wanted to charge more for the new COVERSYL it could have done so, but the government would then presumably not have agreed to subsidise it under the Pharmaceutical Benefits Scheme (PBS) when there were cheaper generic alternatives available.

Whether this reflects "robustness" of the Australian system is no doubt a matter for debate.

I am unaware of any reason to suppose that the claims of improved shelf-life for the arginine salt are untrue, and indeed I can only assume that the allegedly "evergreening" patent would not have been granted without empirical evidence of this fact.

Certainly in the Australian context improved longetivity in "extreme" conditions is a genuine advantage. Indeed, it might even have justified a slightly higher price per unit, considering the potential savings in transport and storage.

By way of comparison, Australian consumers can expect to pay up to $17.63 (£10.85) for 30 Coversyl 2.5mg or generic Perindropril 2mg; up to $23.04 (£14.19) for 30 generic Perindropril 4mg (I could not find a listing for Coversyl 5mg, so it may not be available here); and up to $29.24 (£18.00) for 30 Coversyl 10mg (no generic equivalent listed in this dosage).

These are PBS-subsidised prices, so the Australian taxpayer is also contributing. It therefore seems that whichever brand you choose, the British consumer is doing better than the Australian, despite our allegedly "robust" system.

Swings and roundabouts, perhaps?

Dr Mark Summerfield said...

Some references for info/data in my previous comment:

Servier Laboratories, New COVERSYL Formulation, 3 July 2006.

Pharmaceutical Society of Australia, Coversyl reformulation generates confusion, 25 October 2006.

Search results for PERINDOPRIL in the current Pharmaceutical Benefits Schedule.

Anonymous said...

There is another important issue here. Sometimes the same drug is formulated differently by a generics company once the patent expires on the drug compound itself. In addition to effects on stability to storage, differences in galenic formulation and between the various salts may well affect the pharmacological profile of the drug as well.

Consequently, it is not uncommon for patients moving from a previously patented drug to the generic version after patent expiry, to find that the same molar dose of the same drug has different therapeutic efficacy and a different side effect profile. This derives from the different galenic formulations employed by the originator company and the generics company. There is also a psychological element, in the sense that the patient is given a different box with a different name, however, this can be eliminated by double-blind trials to test the different effects of the different formulations.

Indeed the galenic formulations may also be subject to separate patent rights with a later expiry date than the patent on the original drug and not necessarily belonging to the same company.

Jennifer Kepler said...

Very interesting posting today. I usually prefer to purchase generics over the name brand, but, like many consumers, I too have fallen prey to marketting and though logically know that their is no chemical difference between my favourite trademarked cold remedy and the generic store brand equivalent, for some items I still prefer to buy the branded version. Thus for some consumers it is not a matter of whether or not the patent has expired and consequently the products are the same, but rather a sense of security or trust you have with the products of the former patent holding manufacturer.

That being said, not all generics are true equivalents (many patients have drastic lab value differences when switching from Coumadin (tm) to warfarin (generic. And our health care providers most be ever diligent to know when a generic is perhaps not appropriate for a given patient, hence the use of DAW on prescriptions (dispense as written).

Anonymous said...

I find the argument of "evergreening" a trade mark, of all things, quite odd.

Trade marks, when marketed properly, create customer loyalty in every sector. Once it has been established, the proprietor will seek to maintain -or evergreen, if you will- that loyalty.

I find it hard to see what's so different in the pharmaceutical sector. Patients and doctors not properly researching whether a generic alternative is available?

Finally, a word regarding the argument that "no higher benefit to the patient" is obtained at a higher cost. Firstly, if a patient or doctor has more confidence in products bearing a trade mark that he knows, that confidence represents the brand's added value. Secondly and even considering no added value is created, the same again holds true in other sectors. Smell-alike perfumes are abundant on the market. Yet, some people remain willing to pay excessive prices for the corresponding luxury perfume. What's the difference?

James Wagner said...

"Firstly, if a patient or doctor has more confidence in products bearing a trade mark that he knows, that confidence represents the brand's added value."

I guess the question is are the Docs being confused into prescribing the argenine salt when they intended to prescribe the erbumine salt?

If so, where does control over the mark to transition the brand end and misleading the consumer begin?

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