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: