Wednesday, August 27, 2008

More Exposure of Trouble at the FDA

No doubt, you have read about the brew ha ha over the type 2 diabetes medicine Byetta being linked to pancreatitis which lead to the death of a few (I believe around 6 cases at the last count, out of over a million prescriptions worldwide). In fact, last night at 5:00 PM, Amylin Pharmaceuticals and Eli Lilly and Company (who jointly market Byetta, known generically as exenatide) held a conference call intended to do damage control on the issue. Lilly, in particular, depends heavily on Amylin's Byetta to fuel its sagging diabetes business. The company continues to lose market share in insulin to rivals Novo Nordisk and Sanofi Aventis largely because Lilly is the only one of the big 3 insulin makers who offers only a rapid-acting insulin analogue, but in order to win business from insurers and pharmacy benefits managers (PBMs) who pay for 80% of the drugs sold, they need to have both a rapid-acting analogue and a long-acting analogue and Lilly offers only one of these. Earlier this year, Close Concerns reported that Lilly was returning to the drawing board to develop a Lantus-like product, but even under ideal circumstances, it will be years before any such product is introduced.

As might be expected, rival Novo Nordisk's stock also took a hit on the Byetta news. The company this year sought U.S. and European regulatory approval to begin selling liraglutide, a very similar drug relative to Byetta (some would call it a "me-too" product), and made a very big deal about it at this year's ADA Scientific Sessions in San Francisco to build positive impressions among doctors for the yet-to-be-approved drug.

The "news on Byetta suggests potential risk with the development of other GLP-1 programs, including those by Novo Nordisk," Jack Scannell, an analyst at Bernstein Research, said in a note to investors. "Regulatory delays, greater scrutiny and tougher labeling with these programs would represent a source of downside."

Novo Nordisk went into overdrive the day the FDA warnings about Byetta were announced. Within MINUTES of the announcement, Novo responded with a press release. Novo Nordisk Chief Science Officer Mads Krogsgaard Thomsen told Reuters on August 19, 2008 that although there had been cases of pancreatitis in patients treated with liraglutide, Novo had "not seen a statistically significant increased frequency" in patients treated with the drug. So Novo admits that their drug also caused pancreatitis, but tried to spin the story to make it appear less concerning.

All of this points to an undeniable fact that the FDA has failed to do its job properly. Back in July, the pharmaceutical industry blog Pharmalot featured a story about a new website called Thoreau-FDA.com in a posting called "Civil Servant Disobedience: A Critical FDA Site". I was on vacation at the time, so I didn't really have time to plunge into it then.

If you're anything like me, my first question was about the name -- I remember thinking "what the heck does Henry David Thoreau (think Walden Pond) have to do with drug approval? That, apparently, is a play on words. Thoreau-FDA stands for Thorough – High – Objectivity – Review – Ends – Are – Us – FDA. The website, which is anonymously prepared, is highly critical of the Food and Drug Administration and, in particular, FDA commissioner (and close friend to the Bush Family) Andrew von Eschenbach, who they accuse of oppressing FDA employees and preventing them from doing their jobs properly.

Their objective is "to intensify public scrutiny of FDA upper management's efforts at ensuring public health protection in an increasingly complex global marketplace ... and engage (FDA Chief Andrew von Eschenbach), and/or his successors and other FDA upper managers in a public question and answer dialog ... to end the entrenched process flaws in FDA's pre-approval drug review and post-approval regulatory enforcement systems."

That's a very tall order, to be sure.

We have been told that the FDA's approval process for drugs follows a prescribed path, and all drugs go through the same process. But what these former FDA folks argue is that senior-level managers at the FDA routinely meddle in the approval process by intimidating lower-level employees with "off-the-record" mandates on what they should be finding (and looking for) in the clinical trial results. The bottom line is that many employees at the FDA are intimidated by managers to overlook apparent dangers because the boss says to. Worse, because these mandates are not documented, it gives the appearance that the lower-level FDA researchers are the ones making the recommendations, not the head honchos at the Agency. A slide show presentation on the real "approval process" is documented on the main page of the Thoreau-FDA.com website under the heading "PRIMER ON DRUG DEVELOPMENT", and I highly recommend reviewing it to see what is going on at the Agency which is supposed to be protecting us from harmful food and drugs.

The site is chock full of information, including a few videos worth watching. The identity of most of the people in these videos is protected so they do not lose their jobs, but their message is clear: there is growing discontent among the rank and file with the shady dealings going on at the FDA (which ironically enough is staffed with many former pharma people) which puts public health at risk yet favors the interest of big drug companies. Have a look at this video:

6 comments:

Anonymous said...

Good reporting, Scott. While Byetta may or may not be headed for more serious problems, the MEAT of the problem is the flawed FDA, and its equally flawed AE reporting system.

Thoreau-FDA is to be commended for shining the light on systemic failures within the agency . . . but the public is asleep. As the pre-emption (for medicines) debate is heating up, the public MUST WAKE UP. The fox has--for way too long--been in charge of the henhouse.

Thanks for blogging and keeping us informed.

--Melody

Jenny said...

Unfortunately, all this negative press about the 6 cases of pancreatitis linked with Byetta will cause MORE prescribing of a far more dangerous drug, Januvia.

Dr. Mark R. Goldstein who publishised a letter about this in Annals of Internal Medicine (Read it HERE estimates that Januvia is causing 30,000 excess cancer deaths a year. But because the only cancer tests the FDA requires do not track human cancers longer than 1.5 years and hence did not track the long term effect of blocking the protease, DPP-4, which is essential to killing metastasizing cells, these excess deaths will not even be linked to Januvia.

The FDA's tests only look for drugs that cause cancer in the test tube by damaging DNA or in rodents, not cancer caused by turning off cancer-preventing mechanisms. The latter is what Januvia does.

And Januvia is the single most heavily promoted non-psychiatric drug in the U.S. right now and the one with the most new prescriptions.

Byetta is a LOT safer in contrast, not to mention more effective.

Scott said...

I agree Jenny ... Januvia is a drug that is overpriced and far more dangerous, but I think the issue of corruption at the FDA is simply undeniable in whatever case. Its time for radical reforms, the question is whether anyone in Washington is really listening. Whose bright idea was to add tobacco to the FDA's responsibilities? I think splitting food and drugs would be a better decision, not adding to their responsibilities, but instead we see more of the same, which is indicative of a much larger problem with corporate-owned influence.

Anonymous said...

Lilly was returning to the drawing board to develop a Lantus-like product, but even under ideal circumstances, it will be years before any such product is introduced.

I would suggest that Lilly direct its research toward finding a medicine to cure STUPID. I would then recommend that their corporate leaders comprise the base for clinical trials. If they could CURE corporate stupidity, they might once again be a leader in diabetes healthcare.

Like a dog chasing its tail, they seek to only to embrace "new technology" to find that next great blockbuster. All they truly have to do is look in their own CORPORATE ARCHIVES. Per their own research scientists and patent-holder, [patent #5,534,488]:

"The ideal insulin formulation to deal with this basal glucose output would be one that resulted in a slow, steady infusion of insulin into the bloodstream that matched the low level of glucose output from the liver. In terms of this ideal basal time action, the best parenteral [non-oral administration] product that fits this description is commercially available beef Ultralente insulin. Injected just once per day, it gives a low, steady release of insulin into the bloodstream without any noticeable insulin peak."

Lilly is spending untold amounts of money and inexcusable time delays to re-invent the wheel. They HAD the 'gold standard' insulin for basal control, it WAS commercially available--and they TOOK IT AWAY FROM US! How smart is that? Indeed--they need a pill for CORPORATE STUPIDITY.

Lilly might also take note that this NATURAL INSULIN PRODUCT, when highly purified, would not need further testing or FDA approval.

Couple this with the fact that they could literally name their price (up to a point), because it is generic, those pharma/insurance 'selector' groups would see this as a huge price advatage over analog pricing. In fact, if the GENIUSES at Lilly wanted to, they could probably add a vitamin/supplement, creating a patented product that would gain further price advantage. For example--consider what BAYER just did with their low-dose aspirin. They added a phytosterol. Though 'aspirin' was not patentable, I expect their new heart-friendly product is patent-protected. Think what a low-dose insulin with a supplemental bG moderator could do for the diabetic population and the corporate bottom line.

Yes indeed, I think Lilly's leaders could use a high-dose pill to reduce STUPID.

--Melody

Anonymous said...

Scott—

As you know, much of this problem with the FDA had its early beginnings in the journeymen politicians left over from Tricky Dick in the early 1970s. They ended up as henchmen, responsible for all this grief that is firmly rooted in the Reagan administration. Trickle-down economics was just THAT for the middle class—a trickle. At the same time, Reagan employed these henchmen to de-regulate as many business/regulatory systems as possible.

The best example for many of us who are diabetic is the FDA’s looking the other way thanks to the likes of Henry Miller and Vice President George Bush (Sr.) when Lilly’s new rDNA insulin was approved. Of course, there was a gentleman named Donald Rumsfeld, who was a G.D. Searle executive, and (contemporaneously) saw HIS golden opportunity to bring us all the neurologic toxin aspartame, better known by diabetic and weight-control enthusiasts as NutraSweet. These two products alone, approved by the FDA, have probably killed more people than any terrorists will ever kill in the U.S. Add to that the chronic disease symptoms that these products exacerbate and extend, and you have a double whammy (can you say ‘profit-profit-profit’) CAUSED by de-regulation and politicization. It was no fluke that Dan Quayle, tied to Indianapolis and Lilly, was selected to be George H.W. Bush’s vice president. As you aptly pointed out, the present (Bush Jr.) leader has also done everything possible to de-regulate the regulatory guidelines used by our FDA. This also serves the Republican party, when they claim that ‘government can’t do the job, it needs to be done by private/corporate structures.’ So far, Bush’s administration has done nothing but sabotage regulatory with asinine appointments and non-scientific ideologies.

Whether or not embryonic stem-cell research will lead us to a cure . . . just think how much further along we would be in this determination if roadblocks had not delayed the research for the past 8 years. The Thoreau-FDA site which you reference is a very good starting point for all of us to secure our bearings and support those in middle and lower ‘management’ positions at the FDA—you know, those civil servants who actually seek to SERVE. This debacle could be fairly titled, “Follow the money.”

--Brent

Anonymous said...

Scott—

As you know, much of this problem with the FDA had its early beginnings in the journeymen politicians left over from Tricky Dick in the early 1970s. They ended up as henchmen, responsible for all this grief that is firmly rooted in the Reagan administration. Trickle-down economics was just THAT for the middle class—a trickle. At the same time, Reagan employed these henchmen to de-regulate as many business/regulatory systems as possible.

The best example for many of us who are diabetic is the FDA’s looking the other way thanks to the likes of Henry Miller and Vice President George Bush (Sr.) when Lilly’s new rDNA insulin was approved. Of course, there was a gentleman named Donald Rumsfeld, who was a G.D. Searle executive, and (contemporaneously) saw HIS golden opportunity to bring us all the neurologic toxin aspartame, better known by diabetic and weight-control enthusiasts as NutraSweet. These two products alone, approved by the FDA, have probably killed more people than any terrorists will ever kill in the U.S. Add to that the chronic disease symptoms that these products exacerbate and extend, and you have a double whammy (can you say ‘profit-profit-profit’) CAUSED by de-regulation and politicization. It was no fluke that Dan Quayle, tied to Indianapolis and Lilly, was selected to be George H.W. Bush’s vice president. As you aptly pointed out, the present (Bush Jr.) leader has also done everything possible to de-regulate the regulatory guidelines used by our FDA. This also serves the Republican party, when they claim that ‘government can’t do the job, it needs to be done by private/corporate structures.’ So far, Bush’s administration has done nothing but sabotage regulatory with asinine appointments and non-scientific ideologies.

Whether or not embryonic stem-cell research will lead us to a cure . . . just think how much further along we would be in this determination if roadblocks had not delayed the research for the past 8 years. The Thoreau-FDA site which you reference is a very good starting point for all of us to secure our bearings and support those in middle and lower ‘management’ positions at the FDA—you know, those civil servants who actually seek to SERVE. This debacle could be fairly titled, “Follow the money.”

--Brent