Why Drugs Cost A Lot

In my pharmaceutical career, I have worked with many talented scientists and managers. We have all been trying to discover, develop or sell innovative new drugs to address real medical needs. This is a very long process - often upwards of ten years between research discovery of a "lead compound" and launch of the marketed drug. Finding a new blockbuster is highly unlikely.  Many pharmaceutical scientists go through brilliant careers, and add greatly to the world's scientific knowledge, without discovering anything that makes it to the market. I certainly managed that last clause.

But failure in drug R&D is not (usually) due to ineptitude.  To a first approximation, all drug candidates fail - often very expensively in late-stage clinical trials or, even more disastrously, after launch (eg Vioxx). Even if the drug candidate works well against its biochemical target in an in vitro ("test tube") setting, it will most likely be inactive in vivo (real life) and will often be downright toxic. When I worked in antibiotics research, I personally discovered several, chemically-interesting, new ways to kill bugs.  The problem was that my wonderdrugs always killed cultured mammalian cells just as effectively as they killed bacteria or fungi.  Since I consider myself a cultured mammal, I wasn't going to try the Jekyll-and-Hyde route to further testing.

New drugs have to be safe, especially if they treat non-life-threatening conditions.  They are tested until such time as we can think of no more feasible precautions to take.  Only then will drug regulators allow them to be sold.  Pharmaceutical R&D is therefore a high and inhospitable plateau of expensive and sustained failure, with very occasional peaks of scientific triumph. 

All of the this adds up.  Scientists and their equipment are not cheap.  Clinical trials can cost ten thousand dollars per enrolled patient. These are fixed costs - payable whether the drug is a new blockbuster or a very expensive addition to the universe of known placebos.  The tiny number of successes have to repay the costs of all the failures and the "opportunity costs" of not doing something more productive with the investors' money.  That's why, on average, the true development cost of a new drug is probably close to a billion dollars.

That's also why innovative new drugs have to command relatively high prices. Is the pharmaceutical industry as efficient as it could be at R&D? Does it spend too much on selling and promotion? Do branded drug prices need to be quite so high?  Those are separate questions.

Le Plus Ca Change...

...Le plus c'est la meme chose.  Today is the last day of the Florida anti-counterfeiting conference.  It has been well organised and attended by a good mix of interesting and senior people with a lot to say about counterfeit medicines. There have been new developments in tactical approaches to anti-counterfeiting which will make a difference in the detection of fake drugs. But, strategically-speaking, I feel as if I've seen this deja vu somewhere before.  In recent years things have not moved on at the pace that the increasing risk to patient safety warrants.

There are some noble exceptions.  Nigeria, for example, is doing great work.  Dr Paul Orhii, Director General of their drug regulator NAFDAC , gave a good insight into how his country is tackling the counterfeit threat using hand-held devices to differentiate real from fake drugs in the field.

The real quantum leap in approach will only come when a global, or at least multi-regional, approach is decided upon, authorised, funded and rolled out.  At the moment we are still in the realm of individual, relatively small pilot studies which show the potential of Technology X in a controlled environment.  We need to take a deep breath and implement a drug verification system on a wide scale, exposing it to the real world threats of criminal attack and realising that it may not be perfect first time.  Only by road-testing and refining such systems can we start to make a real difference.  The current drug traceability projects, though laudable, are the equivalent of learning to drive on a private road.  We know how to work the car, but we need to get used to traffic on the highway before we can go very far.

Google's VIPPS-Accreditation Requirement for Internet Pharmacy Advertisers

The US National Association of Boards of Pharmacy, as well as the Partnership for Safe Medicines and others, have welcomed Google's decision to require accreditation for internet pharmacies wishing to advertise on Google.

The VIPPS scheme for accreditation goes a long way to stamping out rogue pharmacies and Google's decision is a major step forward. It won't stop bogus phamacies appearing in search results, but it will stop them getting on the sponsored slots at the top and side of the screen.

My recent post on parallel universe issues applies here and we need to careful that criminals don't spoof the VIPPS online accreditation symbols. Nevertheless, this is a big step forward.

Will JUPITER Change Pharma's View of the World?

On Monday, the U.S. Food and Drug Administration approved Astrazeneca's  cholesterol-lowering medication Crestor (rosuvastatin) for some patients who are at increased risk of heart disease but have not been diagnosed with it. The decision was based on results from the JUPITER study, which compared over 15,000 patients - half of whom received Crestor for two years and half received placebo.  
The study looked at men over 50 and women over 60 who had an elevated amount of high sensitivity C-reactive protein (a known risk factor for inflammation and atherosclerosis) and at least one additional factor such as smoking, high blood pressure, a family history of premature heart disease, or low amounts of HDL ("good") cholesterol.

Crestor is a statin in the same class as drugs made by Pfizer, Merck and others, but the first to be licensed for such widescale "primary" (ie  before disease onset) preventative use. We can expect the sales of statins generally to increase on the back of this data, and it will be a big boost to AZ in particular.

Some will be critical of the trend to mass medication of the apparently healthy, but if there is solid evidence of benefit then I don't see the objection.  The challenge will be "adherence", the industry term for persuading people to keep taking the medication long-term. When the patient feels healthy and all they see is the drug cost, there is a temptation to stop medication, or to skip doses to make it last longer. 

This is where other patient support and testing services come in.  On a wider level, the move to large-scale primary prevention may mark another step in the integration of the drug industry with life-long healthcare services - what I have previously called "Healthcare as Total Service", or HaTS. It's not always possible (eg cancer) but, as a commercial model, keeping people healthy makes a whole lot more sense than only treating them when they get sick.

Fat Profits For Counterfeit Victoza?

The newly approved Novo Nordisk product, Victoza(R) is set to be a blockbuster. Indicated for type II diabetes, in conjunction with exercise and diet control, it addresses a huge and growing global market. As we collectively get fatter and the prevalence of type II diabetes goes up, there will be a rising demand for products like Victoza(R) and this looks like a good step forward in treatment.

However, the internet buzz about Victoza(R) giving more effective weight loss than existing therapies such as GSK's Alli(R) will also drive demand for "off-label" use - by people who don't have type II diabetes but want a more effective diet pill. Since physicians are not supposed to prescribe Victoza(R) for weght loss alone, there is a danger that people will look for it in unofficial channels such as internet pharmacies. 

New "lifestyle drugs" always attract counterfeiters into the market, eager to exploit the embarrassed and the unwary. Don't get Victoza(R) from anyone except your regular physician. If you need it, you'll get it, but if she won't prescribe it, that's for good medical reasons. Don't risk your health by looking elsewhere.

Tips for Avoiding Fake Drugs

Don't fall victim to counterfeit drugs.  Here are some of the things to think about when buying and consuming drugs.

• Do I need this particular medication?
Many medical conditions are accompanied by internet myths and legends regarding supposed new treatments or cures. Aimed at the desperate, these can lure the incautious into putting faith in untried remedies. The first step in avoiding counterfeits is to seek the advice and endorsement of a qualified medical practitioner for any medication you wish to take.

• Is my desired medication approved and available in my country?
If you live in a developed country, and your national regulator has not approved the medication you want, there is likely a very good reason. If you live in the United States, you are part of the world’s most commercially attractive and profitable medical marketplace. Manufacturers usually want FDA to approve their drugs so they can gain access to the US market. If the drug doesn’t appear on the FDA approved drugs database, known as “Drugs@FDA” then this is a major warning sign.

• Is my source and method of purchase a safe one?

There are reputable internet pharmacies, but unfortunately on a global basis these are in the minority. There are a large number of bogus sites which may be involved with various criminal activities including money laundering, selling counterfeit products, credit card fraud and identity theft. Order drugs via the internet only with extreme caution. Unless the identity of the site is known and can be fully verified (by making a call to a pharmacist, for example) then it is safer to assume that it is not a genuine site.

Beware: counterfeiters will also fake their online accreditations. Take nothing at face value and check everything out until you are satisfied. Has the site asked you for a medical prescription or other documentation? If you are asking for medication which requires a medical prescription in the jurisdiction in which you live, and you have not been asked to provide any paperwork, then ask yourself why not?

• What does the packaging look like?

Does it look as though it has been opened or tampered with? If there is a plastic “shrink sleeve” around the neck of the bottle, check that it looks like an original and has not been re-sealed in any way. If it is a liquid product with a rubber seal, look for needle holes or damage to the aluminium collar. Does the package or bottle look scuffed or dirty, like it has been recycled? Criminals sometimes re-use medical trash. If you’ve used this drug before, does the packaging you received this time look exactly the same as previous ones? Look for small differences – different fonts, changes in text size, mis-spellings, colour changes, logo not quite right etc. Is the manufacturer’s label on straight, as it should be for machine-labelled genuine drugs? If not, it may have been re-labelled by hand.

• What does the product itself look like?

Does the shape and size of the pill look right? Is it the same as last time? Do the pills all look the same as each other? Genuine drugs have a consistent appearance.  Are the pills cracked or chipped or crumbling?Has the pill colour changed compared to previous prescriptions? Manufacturing of genuine medicines is highly controlled and they should look the same every time. Even subtle changes from the usual appearance can indicate fake product

• When taking the drug:

Does it smell or taste different? Does it behave unexpectedly (e.g. dissolve differently)?

• After taking the drug:

Did you experience any adverse effects? Minor but unexpected effects (headache, nausea, dizziness etc) from a new batch of a medication, which you have taken regularly without previous problems, may be a sign of fake or sub-standard drugs. More major adverse events should always be followed up with a medical consultation. Often, these events are explainable by other factors, but in some cases fake drugs may be to blame. If you have an adverse event, keep all drug packaging and tell your medical practitioner of your concerns.

Photo: zimpenfish

Alli Money

The FDA issued a warning recently about fakes of the GSK weight loss product Alli in the US, apparently bought online.  The weight loss market is a prime target for counterfeiters because many people would prefer to buy online rather than have the embarrassment of a visit to the doctor.

It seems that the counterfeit product contains sibutramine, a potentially dangerous controlled substance.  The outer packaging of the fake Alli was pretty accurate, with only a couple of minor differences to the real thing: a missing lot code and a wrongly formatted expiry date. The other differences were a very slightly different thread on the bottle neck, and a different sealing foil. 

Only when the capsules are broken open does the difference become obvious to the casual observer - the GSK product has neat globules and the fake is powder.  How many of us would have spotted that? Most of the time we just swallow our pills or capsules without a second thought.

This incident highlights, once again, the need for vigilance in rooting out fake medicines.  If it looks wrong, or different from last time, take it back to your pharmacist or report it to the authorities.  FDA has a mechanism for doing just that on their website, as does MHRA in the UK.

And if you are thinking of buying medicines over the internet, my advice is simple. Don't.  There are some legitimate online pharmacies but they are heavily outnumbered by people who would sell you anything to make a buck.