Who knew what when and who cares?

Who knew what when and who cares?

These past few days have been rather interesting for the folks at Amylin (NASDAQ:AMLN), who besides trying to sell the company they must now deal with a series of reports over a memo written by  Mary Parks, division director of the FDA responsible for the review and oversight of diabetes drugs.  In the memo Ms. Parks states; “The initial submission of Bydureon received a complete response action on March 12, 2010. During this review, FDA only identified the requirement for a REMS with Medication Guide and product quality issues as deficiencies to be remedied. FDA was not made aware of a thorough QT (tQT) study that was conducted for the Canadian regulatory authorities in support of a marketing application for Byetta in that country. The time period during which this tQT study was conducted was between April 23, 2008 and July 21, 2008, well in advance of when Amylin submitted its NDA to FDA for Bydureon. More importantly, FDA was not informed by Amylin that Health Canada considered several findings from tQT study concerning enough such that approval was delayed in Canada because agreement on product labeling could not be reached. On April 12, 2008, Health Canada notified FDA of this study and its implications to both Byetta and Bydureon risk assessments.”

This statement from Ms. Parks basically accuses Amylin of intentionally withholding important information from the FDA. On Monday thestreet.com posted a story which went one step further and stated; “Amylin executives lied to investors by failing to disclose that this hidden Byetta heart-safety study played a key role in FDA rejecting the company’s follow-on diabetes drug Bydureon, according to these same FDA records.” The story was also picked up by Pharmalot a well-respected blog which stated; “In a damning disclosure, an FDA official charges that Amylin Pharmaceuticals concealed a study that raised heart safety concerns about its Byetta diabetes drug and then hindered agency access to the data when it was discovered”

Now before everyone gets ready to bring out the guillotine and chop off the heads of Amylin executives, a little perspective and some history.

April 2005 — BYETTA approved in US

Late 2007 — Regulatory authorities in Canada request tQT study for BYETTA.

Mid 2008 – Amylin conducts the tQT study for BYETTA.  Study met criteria in the International Conference on Harmonization (ICH) guidance for a “negative QT/QTc study,” meaning that the dose of BYETTA tested did not prolong the QTc interval, thus no safety signal as evaluated.

April 2009 – Amylin notifies FDA of the study’s title and certain study details in a table as part of the 2009 BYETTA IND Annual Report (a routine submission due on the anniversary of approval for all marketed drugs).  This is the usual process to notify FDA of studies conducted outside the U.S. IND when there is no evidence of a safety signal.  FDA’s process states that they will review that list and notify the company if they need additional information about any particular study.

June 2009 – Amylin presents the results of the BYETTA tQT study at ADA.

March 2010 – Amylin receives Complete Response letter for BYDUREON.  tQT not mentioned in that letter.

April 12, 2010 – FDA reported that Health Canada contacted FDA regarding the BYETTA tQT study.

April 13, 2010 — FDA requested the tQT study details from Amylin.  In a clarifying communication that day, FDA agreed that Amylin would provide the BYETTA tQT data as a submission to the BYETTA IND since it was a BYETTA study.  FDA confirms that they will review the study as part of the BYDUREON NDA.

May 2010 – Amylin completes the submission of the BYETTA tQT study to the BYETTA IND as agreed.

October 2010 – Amylin receives Complete Response Letter for BYDUREON asking for a tQT study to be completed with exposures of exenatide higher than typical therapeutic levels of BYDUREON.

January 2011 – Health Canada approves BYETTA.  Canadian label for BYETTA includes data from the 2008 QT study.

July 2011 – Amylin announces completion of tQT study at higher exposures of exenatide.  Results demonstrated that exenatide, at and above therapeutic levels, did not prolong the corrected QT interval in healthy individuals. Further, the study found no relationship between QTc interval and plasma exenatide concentrations.  Study results submitted to FDA.

October 2011 – BYETTA label updated with data from 2008 QT study.

January 2012 – FDA approves BYDUREON.

What has gotten lost in all this hype and accusations is that both agencies approved the drug and neither felt it necessary to include any warnings in the label based on the results of these studies. Or put another way, this is much to do about nothing.

Diabetic Investor believes the accusation that Amylin executives lied or withheld critical information is ludicrous. What everyone seems to forget is that ever since the Avandia controversy the FDA is ultra-paranoid about diabetes drugs and cardiovascular issues, real or imagined. That it is quite possible Ms. Parks is practicing a little CYA here and is little PO’d that our good friends to north saw something the FDA did not and did something before the FDA did.  Diabetic Investor does not necessarily blame Ms. Park for covering her behind as should something go wrong down the road and she is dragged before Congress she can point to this memo as evidence that it was Amylin who covered up.

It should also be noted that the FDA does not believe there are any cardiovascular issues with Byetta or Bydureon stating in an email to Diabetic Investor; “The company has conducted TWO clinical trials to evaluate effect of exenatide at different drug concentration levels and in both studies there is no evidence for cardiac electrical problems for either Byetta or Bydureon.  In other words, the deficiency on this matter has been adequately addressed by Amylin hence the approval of Bydureon.”

So will someone please explain to Diabetic Investor what all the fuss is about? Can this same person also explain why Amylin executives would lie about this, especially since this is really a non-event? Given the risk adverse nature of almost every drug company and their army of lawyers who scrutinize every single word stated by the company, Diabetic Investor finds it difficult to believe that Amylin executives did not discuss these issues with their legal team. The team at Amylin is many things but being stupid is not among their many talents.

The harsh reality here is that a controversy is much more exciting than what goes on behind closed doors at the FDA. That the people like Ms. Parks are likely getting a little tired of constantly being dragged in front of Congress whenever something goes wrong and never being congratulated when things go as anticipated. It is also true that companies have lied or mislead the FDA and have not always been forthcoming when making public statements. However, these lies or misstatements are usually associated with truly relevant information that is ADVERSE to a drug which is not the case here.

The reality here is that it really does not matter who knew what when and who asked for which data set, as neither agency saw anything that PREVENTED them from approving the drugs. Nor did they require the company to issue any special language in the labels for these drugs.  Put more simply this is much to do about nothing and it’s time we get back to the real important issue of the day – will it be Sanofi (NYSE:SNY), Merck (NYSE:MRK) or another company who acquires Amylin, now that’s a real story.