Rare Afflictions: Medicines or Markets - 04

Move Over Medicines.. time for the Boulevarde of pharmasupra-schemes..

But first, the weekly world edition of The Telegraph often draws a smile at the breakfast table when its resident Matt cartoon makes wry on news. This morning his wit took aim at ‘scientific’ announcements with a couple of blokes depicted at table with a microscope, test tubes and a plate on which was placed a notable vegetable. On the wall behind them a sign read: GM Food. And clutched in his hands a clipboard from which one of them is making an announcement to the world at large. Saith he, “We have developed a carrot that can leap off the plate and punch (someone)—“

Who does not matter, for crackup is already underway and healthily humored peristalsis the better for my digestion.

Yet for the purpose of this blog the cartoon has the added value of serving point on invention and the inventive mind. The former set in context of patent defensibility, the latter in commercial self-interest.

Let’s step back a little..

To US political days of the early 1980s. Senators Orrin Hatch and Henry Waxman had put up a bill to address concerns at branded drugs whose monopoly would lapse as each exclusive-rights-to-sell term expired. Competition was the way. Tried, true, the one-and-only way. BigPharma enjoyed a decade at least for each of its brands, to grow sizeable markets at monopoly prices and after easily recovering R&D costs go on to make fortunes. Giving them wherewithal to adapt and take on the new generics. Lower brand prices, do generics themselves(a subsidiary or affiliate firm to keep more of a market’s revenue) or better, new drugs to keep on the good work..

In 1984 the Hatch-Waxman Act passed into law. Competition the goal it rewarded firms who gained FDA approval and made first filing that a patent was invalid(e.g. timed out) and its product did not breach that patent. With an immediate 180 day exclusive rights-to-sell agreement into markets occupied by the forerunner. Exclusive that is to say from other generics or competitors. Not to be missed, however, would be that such exclusivity also avoided the FDA’s approx. 30 month approval period in respect of other applicants. To wit, first filers had a clear 3 year run into the lapsed patent brand’s market. Opportunity indeed, for it could mean hundreds of millions dollars in a very short time.

Underlining this point and with the benefit of a good deal of experience in the markets since the Act, the Generic Pharmaceutical Association in 2006 said that the ‘vast majority of potential profits for a generic drug manufac­turer materialize during the 180-day exclusivity period.’

Enter the 'Competitors'..

Being patent-holder Solvay Pharmaceutical with its testosterone-replacement brand, Androgel. With market monopoly it was the sole price-setter. Followed in due course by generics firms(Activis is well cited in the case link below).  Who filed per the Act. Only to find itself sued by Solvay claiming patent infringement. Despite which the FDA eventually approved the firm’s generic alternative modeled after the patented brand.

So.. Activis(who had undergone a name change along the way) could either bring its generic to market via the Act’s intended competitive route, or… big surprise (in its day IMO).. promote Solvay’s drug after making a REVERSE PAYMENT AGREEMENT (aka pay-for-delay deal. That is to say, and according to proceedings before the SCOTUS [No. 12–416. Argued March 25, 2013—Decided June 17, 2013 ] receive annual payment from Solvay ranged between $19M and $30M for 9 years).

Nine whole years!! Hey, what is this—what gives—theyse gotta compete not pile on paying patients!! Haven’t they?

Well, my answer to that would take me back to the secondhand goods dealer who was in no mood to haggle prices with a customer one day and bellowed, “I’m in business to make money, mister, not friends!”

And talking about pile, the US Federal Trade Commission have put $3.5B a year on the extra money paid out to patent monopoly pricesetters over and above generics costs. Yes, more than enough money to buy friends.. (lol).

But significantly, pointedly and effectively stifling generics competition and setting up mutually shared patent prices in perpetuity by the Boulevarde’s scheme team

Waitta minute, Federal Trade Commission?, don’t I mean the FDA?

Fraid not, my dear reader, for in this matter the Regulations arm of the FTC holds a very significant brief, and advocacy, role. Well aware as it is, how homeland commercial behavior is subject to global scrutiny in a global world.

By which we could reasonably say that their concern at homeland prices transpose into offshore markets particularly where risk factors such as arise from the above example are calculated and/or incorporated to the US pharmaceutical industry’s advantage. [cf if you will how a storm in the Gulf puts cents on a liter of kiwi gas station gasoline].

The Federal Trade Commission's Pursuit..

We should understand how the FTC is pursuing this matter on a basis of breaking up the logjams arising from such non-competitive arrangements between firms. Its guide is anti-trust law, not as in this case you may be led to believe by Pharmas and their lobbyists, patent exclusivity.

To the precise point then: does patent confer anti-trust immunity?

In the first instance - FTC approach to the District Court - patent exclusivity rules.

In the second instance - FTC to Appeals Court(11th Circuit) - complaint dismissed.

In the third - FTC to SCOTUS re dismissal - UPHELD. Appeals erred in dismissal

As to why the SCOTUS ruling was sought there had appeared a “Circuit split” when FTC pursued and secured a ruling to favor anti-trust action in a similar case—excellent link. Certiorari aka Petition to Review thus arose. Interestingly the 5-3 Supremes decision came by independent ‘rule of reason’ thinking.

Aspects of the decision:—

1. A view that the Appeals Court was fearful of complex expensive litigation- well-expressed in paragraph 4 here

2. How the Hatch-Waxman Act required disputing parties to report settlement terms to .. wait for it.. federal anti-trust regulators..

Suggesting other possibilities that include:—

* Parties do ‘agreement’, not dispute, in their very own workaround for ‘patent’ price prolongation.

* Legislators and their advisors never anticipated reverse payment(RPA) with its connotation of bribery making legal behavior let alone accepted practice.

Both of which appear intolerable. Hence in clear need of resolution. RPA the pro-competitive way may be one satisfactory explanation. Else thoroughgoing litigation via regulators and  plaintiffs which the Supremes guidance may have set in train.

Though such a course is unlikely to prevent further impacts in offshore US prescription drug markets. And ought delay adequate benchmark settings to any trade arrangements until it has a better grasp of clean slate and real world post-Recession needs.


Next time a  peek at the medicines distribution side, distortions caused by make merchants in sizeable patient communities...

003: Bigger Pictures

At lunchtime today I learned from Radio New Zealand's Midday Report segment WorldWatch that IBM - International Business Machines - was 100 years old.

Occasion to remind me of several visits to what the 1980s termed IBM House in a cityside property along Oxford Terrace, Christchurch. I was to learn there how IBM had arisen from "business mergers" and earned its 'big blue' reputation.. and .. wasn't there a computer that could beat any brain anywhere at chess!

Sandwiched between a tree-lined and pretty River Avon at its front and commercial warehousing construction at the rear. Inside, several offices per floor with then fashionable large single rooms divided by multi-partitions whose workstations revealed the firm to have shifted from typewriters, cash registers and office machinery to computers. For them desktop times had arrived.

But, it should be said, IBM was then already behind the times. Technology, and IT, times. Thenceforth they would not catch up, and so far as I know from the radio commentary's conclusion of a present "reinvention" arrived at in ruthless cutting-off-the-past style, this will be insufficient to regain the BAU lead. Kindly put, a phrase to aptly characterize them would be slow followers.

In saying this I'd like to reiterate a term I'd come up with back then yet whose currency in the relevance of a bigger pictures take on the pharmaceutical industry(PI) today in relation to westernized medicine, is a good match.

That term: EMINENTIA.

And taken to mean not what Gould's might give to an anatomical protuberance in the inner ear or a ridge of heart chamber tissue, but a condition arising from eminence. A condition arising despite the best and/or worst efforts of all PI players in westernized medicine, whose 'golden years' were said by a wiki topic as being in the 1990s. A condition which unless recognised  - IMO 1980s - and robustly dealt to as it arises would set forth a rigidity from which so very few would escape. Until too late.

That eminentia is well-and-truly set today for let's say the U.S. pharmaceutical industry is discernible in the context of a Standard & Poors Valuation and Risk Strategies research group report recently made. The PI - and yes largely US-led in this respect - has been embarked on very substantial merger and acquisition programs as it sought also to restate itself in the Health Care business..

Latest data shows how for all business some 828 M&A deals @ ~$93B have taken place. Compared to 2007 - 905 deals @ ~$172B - decline is apparent. Yes, the global Recession in part responsible.

Again all business, when it comes to choice we find Europe taking 45% in 2011(cf 50% 2010); whereas M&A  shot up 85% in target deals around Africa and the Middle East. Whilst for Latin America and the Caribbean the figures were somewhat less.

So much for context. Now for the sectors. Real and vital pointers. For Health Care:

Year-on-year(yoy) @ 2011 Health Care M&A dived. Minus 28%.

We could say how Pfizer's Wyeth 2009 buyout - reportedly the "biggest ever" at $68B - was writing on the wall. Surely?

Perhaps more significant, however, was the nature of that acquisition — cash, shares, loans essential to make the stake. What else might remain in circulation for such activity..? And besides, vigorous take-up in M&A terms does not plenteous opportunity make. But, OTOH, serious - unbuyable - contenders.

Contenders and contention then. Replacing competition..? If yes, eminentia rules. If no, no one rules. Another possibility is the PI remainder stuck and waiting for  upturn in M&A and the industry's so-called leaders pitching their immediate futures in biopharmaceuticals.

Which brings me back to a like theme of the intro. News of a BBC production about 20 vaccines for the future of.. patients or megalo-eminentia?

Next time: Eminentia and Trade, else WTO and rules..

Beginnings: 002

Post-WW1 they had resumed schooling together. She was early teens, he late. Attracted he was for sure. Nothing more fluid in form, style and balance existed in school athletics. Entered in the 150 yards dash, as their peers called it back then, she’d start out of the blocks in front and stay there all the way to the tape. The one to watch. Every audience’s hero in a race, his alone just everywhere else.

Aged 18 her symptoms started.. double vision.. fatigue.. Gotta see the eye man, was early advice. He hardly listened — hadn’t he seen it all before — here, try these prism glasses..  you’ll be fine.. opthalmologist-speak. Fatigue.. why wasn’t that all the running, training. Besides, you are a growing woman and shouldn’t be doing that stuff.. y’know what men do.

Things were beyond argument when her limbs went weak. Found a neurologist, her father soon declared, eminent isn’t the word for him. He has agreed to see you. Only one condition, that you are honest and tell him truly..

Which she did, right after his physical examination. Not hysterical, she told herself and reiterated: “My symptoms, that’s what I’m worried about.” Shown the door for her trouble she vowed henceforth avoid the patronizing patina of perfect fools. Wherever possible.

Worse, and worsening (euphemisms like ‘disease progression’ not allowed), even to the point of being unable turn over in bed, eat properly, likewise for speech. It was her fiancé, now a medical student who came home with a possible diagnosis. Myasthenia gravis.

He knew how this rendered her vulnerable. To a so-called wisdom of the times: No known treatment thus many things to try. - (Disabilities and How to Live With Them(1952). London: Lancet).

Gold injections, thyroid and suprarenal extracts, lecithin, glycine, ephedrine — among a you-name-it brigade — later, and so discharging his extended learning as much as her frustration at false hopes, there came a day she would never forget in 1935.

Living alone save her nurse companion she declared herself indifferent to another injection. A new substance her fiancé enthused. In minutes this changed to a strange feeling. As she was to put it, “ When I lifted my arms, exerting the effort to which I had become accustomed, they shot into the air ... every movement I attempted was grotesquely magnified until I learnt to make less effort... strange, wonderful, and at first very frightening ... we danced twice round the carpet. That was my first meeting with neostigmine, and we have never since been separated.”

Neostigmine is an anticholinesterase drug. Its use is also diagnostic for myasthenia gravis, dramatic relief of weakness and fatigue confirming this disease.

Implicit to its use is knowledge of the biochemical balancing act a body performs by way of the central nervous system(CNS)—motot neuronal—muscle set ups. Body release of acetylcholine makes it the primary driver of nerve ending/muscle action.

This is not of permanent duration in and of itself, being reduced - hence controlled - by cholinestrase. Too much cholinesterase makes for too little muscle action via acetylcholine. The weakness, fatigue and loss of muscular function MG’s attendant and consequential symptoms.

So.. rebalance cholinesterase with anticholinesterase administration and.. and retrain muscles for more normal movement.. and voila!

I smiled, thought: the bigger bolt..  to eliminate slack in those rehaped lopper blade holes.. well not quite but pretty darn good.

He was looking away from me, out the window into the rear garden darkness. Can’t say why yet I sensed his mind upon a small plaque set beneath a tree there. After a long pause he spoke.

“The doctor was her locknut. Drug titrations, watching, always watchful. I mean complementary atropine to keep a check on her CNS’s buddy the autonomic.. and then those too much (cholinergic crisis) times including ats knocking up the rebalancer..”

“You were her doctor,” I said slowly, quizzically.

“No, no, I did surgery. But you know that. Her doctor was.. is a friend of ours.. I mean mine.. Look, if you’ve time tomorrow we could mebbe go over there.. drop in.”

He eyed me kindly, his look saying the subject was over, and the tone of his voice tellingly so. “You er.. you don’t happen to play chess do you.. like to help me with an opening I screwed up!”

Next time - 003 - bigger pictures.. contexts.. for trade, industry, jobs, government...

Blind-Siding the Big Trade Blockage

Put a search out for WTO or Global Trade and likely you'll soon discover how little coverage actual activities or any real sense of progress there is. These days.

Nations — the signatories, usually via government cabinet ministers, to WTO or the World Trade Organisation — squabble over important differences and wording/s to legislative documents designed to hold all parties to them and agreements reached. I'd like to say amicably, which was largely how it was in the early stages of WTO's life. But doing so today would misrepresent and mistate realities.

And very clear to observers is that the WTO executive, officers and advisors, along with business and sovereign expertise know this to be a fact.

So much so that an ostensible Trade meeting in Montana, USA, has government ministers airing their opinions on whether WTO's Doha Round break up, and either give up altogether or align interested nations into "something" else as the Honourable Ron Kirk @ USDT put it recently.

And it is that something else — I believe already underway — which is nudging renewed trade impetus onward.

Not that folks in general would know this; nor for that matter the nature of it. Or its drivers!

And this state of affairs has arisen out of distrust and infighting in the other WTO process. Which is to say that constructive commentary and examination needs to know the new ropes.

As I said earlier - first post (looksee) - Tom - does not know those ropes. He makes a solid plausible, albeit bold, case. But it is not based in exactly where and how things are at.

My task here then is to address both the real situation and provision deficiencies arising. With any luck at all our readers can arrive at a doable conclusion from this.

Because it does need a wider audience's correction.