Let's review, SAT-style:

Zyrtec:Xyzal::Claritin:Clarinex

Expect Zyrtec to go OTC as a means of ensuring continued profitability through marketing. (More people buy brand name Tylenol than the generic — same story for Claritin.)

Here's the bottom line: everything that Zyrtec works for, Xyzal will work for, and vice versa. Same side effects, too. And because this is so, you will never see a head-to-head study comparing Xyzal with Zyrtec, because the results will prove that it's just a waste of money. Like Clarinex. Oh sure, there will be a few isolated cases where Xyzal is 0.5% better for 0.1% of the study population, and these studies will be trumpeted, but remember that they're actually meaningless. You'll also see studies that show Xyzal is effective for some obscure condition that Zyrtec was never studied for. Just remember that this is done to make Xyzal seem like something more than a me-too drug, and that if someone bothered to spend the money, Zyrtec would work just as well.

So if you like to waste your time doing PAs or you feel an insane need to throw your patients' money away, prescribe Xyzal. Otherwise keep on using Zyrtec.

This combo is not unlike their Vytorin arrangement, which is actually a pretty decent combination both therapeutically and financially: Vytorin is no more expensive than Zetia by itself, which makes it a good deal for consumers and insurers alike. (And there's also the more mundane fact that there's one less pill to take, and the fact that ezetimibe is of questionable value when prescribed alone.)

Because Claritin is now OTC, it is simultaneously more and less valuable to Schering-Plough. Less valuable because you can't charge as much for it as you could when it was Rx-only because no one would buy it — and more valuable because you've got a potential market limited only by the number of people in the United States. I know I recommend (generic) Claritin pretty regularly. It works well for most people, myself included.

If the pricing is done following in the footsteps of Vytorin — which I suspect it will be — it'll be a nice little niche drug for the two companies, and it'll save consumers money, if not insurers. I don't ever see it being a blockbuster like Vytorin, for obvious reasons.

The inobvious

One thing struck me about this deal after some thought, and it's the new reciprocity between the two companies: Vytorin is inherently more valuable to Schering-Plough because their drug ezetimibe (Zetia) is still protected by patent, whereas Merck's contribution — simvastatin — is not. With this new drug, the roles will be reversed. I don't know what this means in terms of dollars and cents, but Merck's got to be breathing a bit easier now that they're on more equal footing with their partner.

[tags]Merck, Schering-Plough, Claritin, Singulair[/tags]

How utterly snooze-worthy. Now you Europeans can waste your tax dollars money on the drug, too! Hooray!

Bonus Tekturna story:

Doctor writes a prescription for Tekturna for one of his patients. (One of our drug delivery guys, actually.) Gives him a free sample card, even though he doesn't have insurance and thinks he's doing him a favor. He gets 30 Tekturna for free, and the next month rolls around. That'll be $100, please, even with the employee discount I gave him because he amuses me.

He almost shit a brick.

Remember, folks: giving patients a FREE SAMPLE is great, but it's a complete WASTE OF EVERYONE'S TIME if they are without insurance or if their insurance doesn't cover it.

Mr. Delivery Guy comes back a week later with a prescription for lisinopril, after I write him a note to give to his bonehead physician.

Sometimes I wonder…

[tags]Tekturna, aliskiren, Rasilez[/tags]

In fact, I'm not arguing how efficacious it is. I'm sure it works. If it didn't, it wouldn't be approved. I'm merely questioning its place in current treatment paradigms. To explain what I mean, I'm going to use a crude analogy to compare angiotensin II receptor blockers (ARBs) and aliskiren, the only direct renin inhibitor (DRI).

Think of a sink. For whatever reason, you want to keep liquid from going down the drain. Does it make more sense to keep the sink turned off, or to plug the drain directly?

Well obviously if the goal is keeping the drain dry, you'd plug the drain. This is what ARBs do. They prevent specific and non-specific binding at the angiotensin II receptor sites. Tekturna just keeps the sink from turning on and does nothing to block the drain directly. This means there's still going to be non-specific binding at the angiotensin II receptor site. (Incidentally, this non-specific binding is not merely theoretical; if it were, ACEis would be more effective as a class than the ARBs, but instead they are merely comparable.)

Back to my point: Tekturna is more expensive than the ARBs, and it will be for a long time. I don't think having aliskiren as an option is a bad thing. I just question how valuable the drug truly is with less expensive ACE inhibitors and ARBs. Sitting here, it doesn't seem to have a real niche. Would I try Tekturna if nothing else worked? Of course I would. If I were targeting the RAAS, would I reach for it as first-line therapy? Hell no I wouldn't. I'd go for an ACE inhibitor in most cases.

I'm not going to delve into the heated debates about reactive renin production and other similar topics because I suspect that the reality lies somewhere in the middle ground, as it usually does.

In the meantime, I think don't think Tekturna has a meaningful place in current drug therapy. If ARBs do not work, it is unlikely that a DRI will, either. The only time I see it perhaps being useful is if a patient cannot tolerate ACEis or ARBs.

[tags]Medicine, pharmacy, Tekturna, aliskiren, hypertension[/tags]

Then send out the drug reps.

In theory, levalbuterol almost sells itself. At least they won't have to resort to underhanded marketing tactics quite as much.

Will they do it? I don't know. Probably not. That would require doing things differently — like lowering the price right off the bat — and I think we all know how much Big Pharma likes to do things Their Way. Risk is, well, risky.

If I were captain of the ship, though, I'd roll the dice. The inhaler market is huge — and only going to get more lucrative once CFCs disappear — and right now, Sepracor is not positioned to be anything more than a niche player when they could easily have most of the pie.

* Cursory research indicates that some PBMs have the Xopenex HFA MDI at Tier 2 already, but most seem to require a Prior Authorization.

[tags]Medicine, pharmacy, Asthma, Sepracor, albuterol, Xopenex[/tags]

Now that I'm home on a non-firewalled Internet connection, I can actually get real drug information. (How sad is it that I can't do this at the pharmacy?) Aliskiren:

Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known

I'm sure you could play games targeting specific points and pathways in the renin-angiotensin-aldosterone system until the cows come home, but how many of them will be meaningful? Medscape has an article comparing, contrasting, and using Diovan and Tekturna in parallel:

Do we need Tekturna? Would not an ARB plus a diuretic do a better job? There are benefits to combining an ACEi with an ARB, that are fairly well understood. Is Tekturna going to create some sort of super trifecta?

I'm thinking not. Combining an ACEi with an ARB does a couple of things. First off, ACE inhibitors only stop the conversion of angiotensin I to angiotensin II. Blocking the pathway there does nothing to stop any non-specific binding to the angiotensin II receptor sites. ARBs block much of this non-specific binding because the receptor sites themselves are blocked. However ACEis also block the breakdown of bradkinin (which is broken down by ACE) which leads to greater vasodilation, which is why ACEis and ARBs are usually similar is study results. Bradykinins, of course, are a double-edged sword: they may contribute to vasodilation, but they are also responsible for the dry cough and angioedema associated with ACEis.

I don't see how aliskiren is going to add to this. Is there component to the RAAS that I'm not thinking of? Is it not better to attack a problem from many different angles instead of hitting the same pathway three different ways?

The NEJM concludes — along with the rest of the world — that HFA albuterol formulations are more expensive than their CFC counterparts. The article (subscription required) delves into some of the differences between the various HFA formulations as well as the differences between CFC and HFA albuterol.

The article doesn't talk much about ProAir HFA, which I find a bit strange, especially as it has captured 60% of the HFA albuterol market. Unrelatedly, it seems that concentrations of albuterol are slightly higher with HFA than the CFC versions, despite the smaller plume.

Here're some semi-relevant differences between Ventolin HFA and Proventil HFA, emphasis mine:

The excipients added to the propellant formulation differ according to the brand of HFA inhaler. For instance, each puff of Proventil HFA releases 4 μl of ethanol. This small amount of ethanol will not have a discernible clinical effect, but it may be of concern for patients who for religious or other reasons abstain from alcohol. Breathalcohol levels of up to 35 μg per 100 ml may be detected for up to 5 minutes after two puffs of Proventil HFA. Unlike CFC propellants, HFA propellants may cause false positive readings in anesthetic gas–monitoring systems. The infrared spectrums of HFA overlap with commonly used anesthetic gases in the range of 8 to 12 μm. One albuterol product, Ventolin HFA, contains no excipients other than the propellant, a characteristic that may improve tolerability for some patients. However, Ventolin HFA comes packaged in a moisture-resistant protective pouch containing a dessicant and has a limited shelf life once it has been removed from the pouch. Ventolin HFAs have a greater affinity for moisture than do CFCs, which means that water vapor is more likely to enter the canister around the meteringvalve gaskets. The other approved HFA inhalers are less susceptible to moisture permeation and do not require a protective pouch.

Shelf life for Ventolin HFA is 2 months after opening, so it's a mixed bag.

A breakdown:

[tags]Medicine, pharmacy, albuterol, HFA, CFC[/tags]

In the January 15 issue of Clinical Cancer Research, the researchers report that their fledgling test, designed to check whether two genes believed to be tumor suppressors are deleted in cells found in sputum, identified 76 percent of stage I lung cancer patients whose tumors also showed the same genetic loss. Existing sputum "cytology" tests, which look for changes in cell structure, identified only 47 percent of the patients, they say.

While no other simple sputum analysis has found such a high correlation with lung cancer, it is not yet good enough for the clinic, researchers say, and so they are now expanding their test to screen for up to eight genes.

This is pretty cool, and while it may not be good enough for the clinic, it does appear to have greater potential than say, the controversial PSA test for prostate cancer which misses 82% of tumors in men younger than 60, and 65% of cancers in men over 60. While you can't yet make a direct comparison between the two, this spit test does seem like it will end up being more accurate than the PSA test.

The researchers are hoping to drill down to the genes that are specific only to cancer. Current cytology tests show the extend of cell damage, but this doesn't correlate to lung cancer rates because most heavy smokers do not develop cancer. Looking for only the genes involved is a more precise approach to calculating lung cancer risk.

[tags]Medicine, cancer, lung cancer, oncology, genetics[/tags]

In some ways, it is a wonder that the work survived at all. In 1670, at the age of 42, Rumphius went blind. In 1687, his still unpublished manuscript and all of his illustrations were destroyed in a fire that swept through the European quarter of Ambon. Undaunted, he dictated a new version and commissioned artists to draw new illustrations.

Fortunately, the second time around he kept a copy of the manuscript. The original was lost when the ship carrying it back to the Netherlands was sunk by a French naval squadron. Still unfazed, Rumphius continued his work, finishing the last volume shortly before his death in 1702.

The extract shows some efficacy against E. coli and MRSA. It was used in ancient times as a remedy for dysentery.

The seeds of the tree, Rumphius wrote, "will halt all kinds of diarrhea, but very suddenly, forcefully and powerfully, so that one should use them with care in dysentery cases, because that illness or affliction should not be halted too quickly: and some considered this medicament a great secret, and relied on it completely."

Very cool story. I just wish researchers knew more about the active compound itself, and whether it is related to any other antibiotics on the market. I could see it being entirely new or being related to a current antibiotic: it could be from the seeds themselves, which would indicate that it's entirely new, or it could be from a fungus growing inside the seed (think a moldy peach pit), in which case it could be related to current antibiotics. I guess we'll have to wait and see — I don't have access to the BMJ, so any details about the extract itself are hidden from me, if they are even known. Alas.

Geographic isolation can make for some very interesting evolutionary developments. It would be really cool if this was completely new.

[tags]Medicine, MRSA, pharmacy, antibiotics, MDROs, drug discovery, botany[/tags]

"For people with active ulcerative colitis who do not respond to corticosteroids or immunosuppressive agents, infliximab is effective in inducing clinical remission, inducing clinical response, promoting mucosal healing and reducing the need for colectomy, at least in the short term," said review co-author Dr. Anthony Kwaku Akobeng.

[...]

"Infliximab is another option if steroids fail," said Peter Higgins, M.D., an assistant professor in gastroenterology at the University of Michigan Medical Center in Ann Arbor.

And here I was, thinking this was common knowledge. In fact I during my hospitalization a few weeks ago whilst on vacation I had a discussion about UC with the tech doing my CT scan. She was telling me one of her friends had severe UC, and that he was on steroids. I distinctly remember suggesting Remicade or Humira instead of prednisone through my drug-induced stupor. She was telling me he hated the side effects. What a surprise. Then I think I started rambling about monoclonals and the lack of a generic approval pathway for biologics in general. She stopped talking to me after that.

She was cute, too. Really cute.

But hey, more studies are always good. Too bad Remicade is WAY more expensive than prednisone…

[tags]Medicine, pharmacy, Remicade, infliximab, ulcerative colitis[/tags]

HPV types 16 and 18, which are directly targeted by Gardasil, are responsible for 75 percent of all cervical cancer. But scientists found the vaccine also induces an antibody response capable of neutralising strains 31 and 45, which together account for another 8 to 9 percent of cases.

It makes me wonder how much mindshare (and possibly marketshare) Cervarix — the GSK competitor to Gardasil — will garner when it's approved by the FDA. GSK is going to have to work hard to differentiate its vaccine against Gardasil. They'll certainly have their work cut out for them, because you can bet Merck will be testing Gardasil against the remaining 34 strains of HPV (which makes up only a tiny percentage of cases) to see if it has any success there as well. If I were GSK, I'd be thinking about getting some more clinical trials going on strains that Merck isn't playing with yet.

[tags]Medicine, pharmacy, Cervarix, Gardasil, HPV, cancer, oncology[/tags]

"We know that an HIV-AIDS patient needs to take 95 percent of his or her pills or they won't work," said John C. Martin, chief executive of Gilead Sciences Inc., one of the companies in the Atripla project. "So the fewer pills a patient needs to take, the better the outcome."

Even I'm terrible at compliance, and I understand this better than most. I'd love to see some graphs that show the correlation between the number of times per day that a drug is taken vs compliance over time. I bet you see much higher compliance rates for a once-a-day drug than you do with twice-a-day regimens, and an even steeper drop-off when you've got someone who needs to take something 3 and 4 times a day. I bet it's particularly bad with 4 times a day dosing, because then you're not necessarily tying a dose to a specific daily activity (eating).

Hrm.

[tags]Medicine, pharmacy, Atripla, HIV, AIDS, Sustiva, truvada, patient compliance[/tags]

The new vaccine is DNA-based, and if testing continues successfully, Tokyo Metropolitan Institute for Neuroscience in Japan hopes to have a vaccine for use in humans in 6 or 7 years. Jonathan has coverage of the nuts and bolts of how the vaccine works over at Nobel Intent, if you're into that sort of thing.

Elan Pharmaceuticals had been working on an Alzheimer's vaccine several years ago, but they were forced to halt their work due to brain swelling in some of the test subjects. Yoh Matsumoto, the lead researcher on the project says that these problems have been ironed out based on what his researchers learned from the previous failure.

So far we've got cervical cancer vaccines, vaccines for otitis media, and a shingles vaccine. That's a lot of happenings in a field of medical research that has long lay dormant.

[tags]Medicine, pharmacy, vaccines, Alzheimer's, Elan, biotechnology, biotech[/tags]

As a first step, PATH plans a program of research in India, Peru, Uganda and Vietnam, with a $27.8 million grant from the Bill & Melinda Gates Foundation, studying the best way to use the vaccines.

PATH will help pilot introduction in the four countries, and both drugmakers have agreed to provide their vaccines to demonstration projects.

This is excellent news, and it's the right way to go about promoting the vaccine. Best practices for dispensing and usage will lead to greater efficacy and more lives saved in the long term. (After all, a major component of a positive therapeutic outcome is patient compliance — that is, consistent usage in the most effective manner possible in given environmental conditions.) Even better is that it looks like the drug companies will be supplying the PATH project for free during preliminary fact-finding. With the Gates-Big Pharma collaboration, it looks like we can start making inroads against the 200,000 yearly deaths that occur as a result of HPV-mediated cervical cancer.

The first world will largely subsidize the third for the time being, but large orders of the drug could turn a profit for GSK and Merck in the long run, which is why it is in their best interest to provide the drug free of charge for programs like PATH in the beginning. And lest the liberals complain about profiteering off the backs of the poor, consider that the third world is one of medicine's final frontiers: if companies can profit while helping those unable to help themselves — via charitable and governmental financial proxies — then everyone wins. Especially the poor.

[tags]Medicine, pharmacy, HPV, gardasil, cervarix, gates foundation, bill gates, GSK, Merck, cancer, oncology, cancer vaccine[/tags]

This cancer kills 3,700 women each year in the United States and hundreds of thousands more worldwide.

[...]

Gardasil, manufactured by Merck & Co. Inc., protects against the two types of HPV responsible for about 70 percent of cervical cancer cases. The vaccine also blocks infection by two other strains responsible for 90 percent of genital wart cases. It will be available by the end of June.

It is likely that Merck will market Gardasil as a cancer vaccine rather than an STD vaccine for political reasons. There has been some speculation that the religious right would opposed the vaccine if they thought that it would lead to premarital and/or teenage sex. To combat this, Merck launched their "tell someone" anti-HPV campaign several months ago to soften the social impact of the drug before the approval was granted. I'm sure we'll see Merck tie a new marketing campaign for Gardasil into this tell someone HPV campaign to allow a smooth transition from one to the other — despite their assertions to the contrary. Even if a direct connection between Gardasil and the tell someone campaign isn't made, Gardasil is currently the only vaccine approved to prevent HPV, so a woman asking about her doc about HPV prevention is almost akin to her asking for Gardasil — even if she doesn't know it. (Not that this is necessarily a bad thing.)

In any event, this is great news for everyone in the first world and the third. Hopefully this will mean that HPV-induced cervical cancer will finally go the way of polio. This is some of the biggest cancer news in a week already chock-full of cancer breakthroughs.

[tags]Medicine, pharmacy, Gardasil, HPV, genital warts, STDs, cancer, oncology, Merck, vaccine, cancer vaccine[/tags]

Specialty drugs are typically biotech medications that treat complex, chronic conditions and often need to be injected. Spending on such drugs reached $40 billion last year or 19 percent of the total on all medicines, according to Express Scripts Inc., a Missouri-based pharmacy benefit manager.

[...]

The explosive growth is spending on specialty drugs is especially problematic because there is no pathway for generic competitors to enter the market.

While it's true that it is somewhat more difficult for biologic generics to be approved, the vast majority of them are still protected by patents in the United States, so the issue is largely moot for now.

An average prescription for an inflammatory disease costs $1,417.

Drugs to treat blood clotting factor deficiencies such as hemophilia registered a 25 percent spending increase, the second largest rise in the group. Annual treatment costs about $100,000 per patient.

Spending on cancer drugs known as antineoplastics, which were administered outside a doctor's office, rose 19.2 percent, the third largest jump. The price per prescription rose by almost 15 percent to nearly $1,600 on average, making inflation the primary driver of the spending increase.

The points missed by the AP article are that the number of hospitalizations is reduced, spending on marginally-effective drug therapies reduced, complications from multi-drug regimens is reduced, and most significantly, the overall quality of life for these patients is HUGELY improved because of the reasons stated above, as well as the fact that their therapeutic outcomes are better.

While it may cost $1,417 for a month's supply of Humira, it can cost that much for one night's hospitalization. A fact conveniently left out of the article.

Everyone is winning with these advanced new therapies: patients, doctors, insurers, and drug companies. But only if you look at all of the factors involved. Articles like this one make me cringe: just last week I heard a patient say to someone else as she was waiting that she "read it in the paper, so it must be true." People have enough FUD in their lives without the MSM adding to it with horribly slanted "news" articles which are nothing more than regurgitated press releases. (You'll notice the press release says nothing about about the lack of generics being a problem, and mainly talks about how Express Scripts is saving money in the face of higher prices. I guess tossing throwaway additions into a press release counts as journalism these days.)

[tags]Medicine, pharmacy, drug spending, drug prices, bad journalism, journalism, biotech, biologics[/tags]

One of the exciting results announced at ASCO has been the affect of Tykerb on patients who have failed Herceptin therapy. The trial compared breast cancer patients on chemotherapy to those on chemotherapy + Tykerb. The results were that the 320 women who took Tykerb alongside their chemo went 4 months longer than those on just chemo without their cancer progressing. As a bonus, Tykerb is administered orally rather than intravenously.

GSK is expected to submit the findings to the FDA this year, and Tykerb could hit the market as early as 2007. Hopefully Tykerb will not get tripped up like Avastin did under further review. If it remains a success, Tykerb could be a very big seller, and benefit thousands of women in the US alone. In the future, Tykerb could compete against Herceptin more directly.

[tags]Medicine, pharmacy, ASCO, Tykerb, GSK, cancer, oncology[/tags]

Probably both. Yep. It's both.

In the May 8 issue of Forbes magazine, the feature article is about Big Pharma and their marketing efforts. Stories like this are nothing new, nor do they really have anything contructive to say on the topic except to shine a bright light on a problem that has popular appeal. Big Pharma does spend a lot of money on marketing, but is it too much? I don't think so, and consequently I can't resist going through the article and picking out bits and pieces that're off the mark, and the ones that are right on. Yes, this is my idea of fun while being stuck in the lounge of a car dealership, waiting to get my car back…

This article is about 2000 words short, so you may wish to get a coffee before you start reading. Or, you know, go to the bathroom or something.

• The balogna
• Contradictions and lifestyle drugs
• Science or marketing?
• "Me-too" drugs
• Marketing and the game of deception
• Short term profits, long term value and calculated risk
• HMOs to the rescue?
• The problem of medical journals

The balogna

Novartis employs some of the best medical researchers in the world, and they have created such lifesavers as Gleevec, which treats a deadly form of leukemia. But what is the fourth-biggest seller in the Novartis medicine cabinet? No lifesaver. It's Lamisil, a pill for–horrors!–toenail fungus. The main effect of the fungus is that it turns the toenail yellow; it can hurt, but no one has died of this inconvenience.

I don't really see the relevance. Toenail fungus is a heck of a lot more common than the cancers that Gleevec treats. While Novartis could probably jack up the prices for Gleevec to inflate sales figures, there's really no point. In any event, while Lamisil may only be effective in 38% of patients, there's no reason that people with toenail fungus should suffer if they are willing to pay what Novartis charges. That's the great thing about living in a wealthy first-world country: we don't have to put up with things like toenail fungus if we don't want to.

In 2005, Lamisil accounted for $1.2 billion in sales. They spent $100 million on advertising which amounts to 8% of the revenue from Lamisil. That's just good business — and make no mistake, medicine is a business.

Contradictions and lifestyle drugs

Lifestyle drugs, like Viagra and Lamisil sell, and they sell well. They don't save lives, but there's nothing wrong with a drug that doesn't save lives, implying that there is is totally ridiculous. Comparing Lamisil to Gleevec is absurd as well: drugs like Gleevec are already enormously expensive, and they catch lots of flak because they ARE expensive, by the same mainstream media that basically whines that they aren't bigger sellers.

So which is it?

So the MSM is wishy-washy, now what about Big Pharma? Well they're hardly innocent — they're worse than the media, in many cases. At least from a moral standpoint — that nebulous ideal that we'd all like to think is the real driving force behind medical innovation. From a business standpoint, Big Pharma are some of the most conscientious, respected, philanthropic publicly-traded companies out there.

Science or marketing?

"Absolutely, marketing doesn't trump science–this is a science-driven industry," says Scott Lassman, a lawyer for Phrma, the industry trade group.

In theory medicine is a science-driven industry, and while R&D spending regularly trumps marketing spending, this isn't an especial shock — marketing is inherently less expensive than employing hundreds of scientists and paying for clinical trials and researching new therapies. And while Lassman is probably telling the truth, there has certainly been a greater emphasis on marketing since the direct-to-consumer (DTC) advertising restrictions were lifted about a decade ago. And I have lamented just yesterday that drug pipelines are indeed running drier than they have in the past.

This emphasis on marketing isn't ocurring in market bubble, either. The entire market has begun shifting its focus to quarterly earnings rather than long-term health. The recent Microsoft stock downgrade by several analysts because it was going to spend more money on R&D and shoring up its product lines is a perfect example of this. Despite this money being spent to strengthen the company it would hurt quarterly earnings, so it was downgraded by analysts. Absurd. But this is the market that Big Pharma plays in too, and they feel the same pressures that other publicly-traded companies feel. When you're a large pharmaceutical company with a huge market cap, analyst ratings have more of an effect on stock price than does releasing the next blockbuster. Analysts look at more than just drug pipelines, and some of the things they look at have nothing to do with the overall value and health of the company they're looking at. Buy and hold investment strategy is largely a thing of the past.

"Me-too" drugs

The article goes on to talk about Levitra and Cialis: me-too drugs in their own right without a doubt. It should be noted that the drug that these meds are modelled after was an accidental find — sildenafil citrate, the active ingredient in Viagra, was originally developed for pulmonary arterial hypertension (PAH), not erectile dysfunction. It just so happened that just about every male suffered from prolonged erections not related to sexual excitement during drug trials, so the emphasis was shifted to ED because the severity of such a side effect would render it unmarketable. And it certainly has been a success in this regard.

Creating Levitra and Cialis meant easy money for their respective makers, because they were capitalizing on the success of a trailblazer. Not creating me-too versions would have been a disservice to their shareholders. Why throw away easy money when it's staring you in the face? And easy money isn't necessarily bad — businesses are in business to make money, and that's what they do, and Big Pharma is certainly no exception.

Marketing and the game of deception

Some of these ad-driven trials are skewed to pit the sponsor's full-strength product against a weaker dose of a rival pill.

This is true, and seeing these games makes my blood boil. For instance, Prilosec is usually sold in its 20mg form, but when Nexium was released, the literature compared 20mg of Prilosec to 40mg of Nexium. A former AstraZeneca rep told me that this was done intentionally to make it seem more appealing. Milligram for milligram the two drugs are about equally effective, with only a percentage point or two difference — not enough to be statistically significant in the real world. (Nexium and Prilosec, for those who don't know, are essentially the same drug — Prilosec is a racemic mixture (omeprazole), and Nexium is the isolated S half of that mixture (esomeprazole).)

Short term profits, long term value and calculated risk

"Everyone was doing the same thing, so the chances of success got smaller and smaller." Big Pharma "said we were nuts" to test a cancer drug that targeted only 25% of breast cancer patients, Levinson recalls. Now the drug, Herceptin, is near $1 billion in annual sales. "If you are developing novel drugs, you don't need sales forces of tens of thousands."

This is certainly true, and it's no surprise that it's a biotech company (Genentech) demonstrating this principle. The next generation pharmaceuticals are going to be the highly-specific therapies that biotech companies can provide. Biotech still holds the promise that it did back during the bubble days; it just takes longer to get from A to B than early investors were willing to wait.

There needs to be a balance between short-term profits and long term value. This is a balance that I haven't seen Big Pharma strike, yet. Eventually they will, because their long-term survival will depend on it. No analyst is going to give good ratings to a company with a dry pipeline. Schering-Plough lost two thirds of its market cap in the last several years for this reason. Beating the horse for that last burst isn't going to matter when you try to begin the next lap and it dies under you. You need fresh products to perpetuate your survival. And the pharmaceutical industry hasn't figured out the right balance yet. Just like the technology industry, the savior of Big Pharma will likely be licensing agreements with and acquisitions of smaller biotech companies that have developed new therapies. Smaller companies can innovate and change faster than large ones can, but they lack the massive infrustracture (marketing, manufacturing, etc.) that large companies can bring to the table.

Short-term thinking on the part of Lilly, specifically cited in the article as having given up on antibiotics, will lead to it having its lunch in that area eaten by Merck. Merck will have some rough days in the next five years, but they've also got one of the strongest, most well-diversified pipelines of any of the big drug companies, and that is what will ultimately power them through the mess they've created for themselves with Vioxx. Just about every significant breakthrough that I've covered here in the last month has been by Merck, many of them truly significant.

Ad spending certainly has an effect on demand. Patients do make requests and threaten to find new doctors if their current providers don't cave to their demands. In this respect, DTC advertising is bad for consumers. Most of the time, a doctor is better-equipped to make therapeutic decisions than the patients they treat.

HMOs to the rescue?

Ironically, it could be the insurance companies that end up shouldering the burden of the costly battle. Measures have already been put into place to curb unnecessary expenditures. Prior authorizations for non-step therapies, for instance. Doctors know what the rules are, but often don't play by them because it's more convenient for them (and the patient) not to. Why experiment with a low-cost H2 blocker when you can go right for a guaranteed PPI at twice the price? When a prior authorization for an expensive drug is denied, I truly don't feel too bad for the doc or the patient — I've never seen a PBM deny a PA when there was a good reason for a patient to have it.

PBMs have goals that are almost diametrically opposed to those of Big Pharma, so their opposite pulls will hopefully eventually allow the insanity to stop. PBMs don't make money when a patient fills a prescription for an expensive brand-name drug. They make money when the patient opts to do mail order pharmacy with generic drugs. (I hope to have an article on this breakdown in the next month.) So in a way, it's almost a scenario where the enemy of the enemy is your friend. Who "you" is is still up for grabs, and how much of a friend a self-serving business can truly be remains to be seen. Past experience indicates that it only lasts so long as it benefits the corporation's bottom line. To those who lament the greed of big business — it's their job. It's what they're in business to do: make money. So save your ire for something worth it. Like medical journals.

The problem of medical journals

Medical journals are a business as well. Ostensibly, their job is to disseminate clinically-significant data about new therapies to providers so they can make a well-informed decision. The reality is that journals make most of their money by selling thousands of reprints to Big Pharma so they can give them to their sales reps to give to doctors and other providers. In many cases they are just expensive, prestigious marketing tools. (The case of NEJM and Vioxx springs readily to mind.) But they have escaped the scrutiny of the media and even many medical professionals because their role is more passive, their motivations less obvious. They are loathe to issue retractions for many reasons (loss of credibility, loss of money on reprints for the articles retracted, etc.), and in a way their contribution to the problem of medicine and marketing is more nefarious: it's no secret big drug companies are out to make a few bucks. But what about the journals that publish their findings and make these things possible? It would be nice to see the media shine its biased light in their general direction for a change.

[tags]Medicine, pharmacy, Big Pharma, marketing, journalism, advertising, consumer spending, economics[/tags]

This is just the latest trend in a newly-rekindled vaccination industry. Turns out there's money in vaccines after all.

But analysts reckon the vaccine market will grow much faster than the market for prescription drugs. "We're in a period where pharmaceutical sales are growing at 5% to 6% a year," says Novartis Chief Executive Daniel Vasella. "In contrast, the vaccine industry is looking at nearly 20% annual growth over the next five years."

I tend to take what analysts think with a grain of salt, because I get fed up with their near-obsessive emphasis on quarterly earnings, but they're probably right in this case. Biologics are heating up, and vaccinations are a big part of this. Along with expensive, niche biologic drugs, vaccines will probably be consistent money-makers for Big Pharma. The reason for this is is that it's quite difficult to get a generic biologic approved by the FDA. It can be done, but the FDA had to create a new way to approve these "generics," but this precedent of sorts may not hold water for other biologic generics:

The FDA said the approval did not set a precedent for other copycat biologics. Human growth hormone is one of the better understood protein compounds, making it possible to compare brand name and generic versions, it added.

"The approval of Omnitrope … does not establish a pathway for approval of follow-on products for biological products … nor does it mean that more complex and/or less well understood proteins approved as drugs under the Food, Drug, and Cosmetic Act could be approved as follow-on products," the FDA said in a statement on its Web site.

Unfortunately I cannot find the source of the quote, but in any event, it will be interesting to see what happens when more biologics start going off-patent. Will they still be big money-makers for Big Pharma due to bioequivalency issues? Or will have generic drugmakers have figured out ways around these potential roadblocks by that time?

It's easy to think that the generic companies will have figured something out by then, but I am reminded of the bioequivalency issues that generic manufacturers had with drugs like Lanoxin (digoxin) and Synthroid (levothyroxine) for quite a few years. It's not as easy as firing up a photocopier, particularly with complex biologic drugs.

It's a clear victory for Big Pharma, and a loss for consumers and any company that's not Sanofi-Aventis or BMS. Plavix was #2 on the top 200 list in 2005, with sales totaling $5.2 billion. Had Apotex been successful and not settled out of court, there would have been a generic Plavix available relatively quickly. Unfortunately they settled for the guaranteed money, and exclusive rights for 8 months. As I've said before, the value of the generic drug market is tiny compared to Big Pharma — by taking the settlement BMS, S-A, and Apotex all win. (Personally if I was Apotex, I'd have pushed for a higher figure, just because Plavix is so valuable.)

As soon as the results were announced, ten lawsuits by health plans, unions, and other businesses were immediately filed in retaliation, alleging the deal violates federal antitrust laws. The FTC has said that they will examine the case to see if there are any laws being broken. Frankly, I don't know enough about antitrust law to speculate whether the new round of litigation holds any water. It will certainly be an interesting case to watch, and has implications for further back-room licensing deals between major pharmaceutical companies and generic drugmakers, though nothing as unique as this has happened in recent memory that I am aware of.

Don't be surprised to see the number of similar lawsuits mushroom over the next five years as pipelines run dry and patents expire — it will be the only way Big Pharma will be able to maintain their otherworldly revenues for a precious few extra years. I have not seen a change in the way Big Pharma conducts their R&D efforts, and even if they did, there would still be a multi-year dearth of new drugs in the near-term. The path Big Pharma chose back when direct-to-consumer advertising restrictions were lightened has resulted in fat profits when their focus shifted to marketing instead of R&D. Unfortunately for them and everyone else, this more litigation and fewer breakthroughs.

[tags]Medicine, Pharmacy, Sanofi-Aventis, BMS, Plavix, clopidogrel, Big Pharma, antitrust law[/tags]