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,TheStreet reports, citing newly released FDA documents. And later, Amylin execs purportedly lied to investors by failing to disclose that the Byetta study played a key role in an agency decision to reject the Bydureon follow-up treatment.
The Bydureon review and approval was a "long and complicated process, in part due to Amylin's withholding of information on Byetta that FDA deemed to be important to its evaluation of the safety and effectiveness of Bydureon," according to a January 2012 memo written by Mary Parks, division director of the FDA office that is responsible for diabetes drugs, TheStreet writes in its expose.
Since Byetta and Bydureon contain the same active ingredient, Amylin asked FDA to rely on efficacy and safety data from Byetta clinical trials for part of the Bydureon regulatory review, and the agency agreed. Bydureon was submitted for FDA approval in May 2009, but rejected in March 2010, since the FDA wanted a completed risk management plan and resolution of some product quality issues, TheStreet continues. But then, FDA officials received a surprise.
In April 2010, Health Canada told the FDA about a "thorough QT study" of Byetta conducted that Amylin conducted two years earlier (the January 2012 has a typo; the disclosure was made in April 2010 and you can read more here). Such a study measures the effect a drug has on heart rhythms, a key issue given FDA concerns about cardiovascular safety of diabetes drugs. And this particular study raised significant such concerns among Canadian regulators, TheStreet writes.
But Amylin never told the FDA about the study or include the data in its initial Bydureon filing, even though the drugmaker agreed to supply Byetta safety and efficacy data for the Bydureon review, according to the memo. "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," Parks wrote.
At that point, the FDA asked Amylin for the study data as part of its resubmission, which was made on April 22, 2010, but the Byetta tQT study were "absent" from the filing, Park states in her memo. "Instead, the results and datasets... were submitted on April 15, and May 13, 2010 to the Byetta IND (which was the original Byetta regulatory filing). Regardless, FDA reviewed it as part of the Bydureon NDA," she wrote.
An Amylin spokeswoman tells TheStreet that the FDA was notified in an "appropriate manner" about the study. "Amylin is committed to being transparent with regulatory agencies, the patients and physicians who put their trust in our products, and our investor community," the spokeswoman added. "Our interactions with regulatory agencies have been, and will continue to be, forthright and timely. Throughout the Bydureon review process, Amylin responded appropriately to requests for additional data."
What happened next? In October 2010, the FDA rejected Bydureon for a second time, partly over safety concerns raised by the study and told the drugmaker a new tQT study was needed. The rejection surprised investors, since Almylin execs maintained there were no cardiovascular safety issues. In fact, TheStreet notes that Amylin ceo Dan Bradbury insisted the FDA reasoning was surprising in a conference call with analysts held after the rejection was announced.
"I would just be clear that it was only on receipt of the complete response letter that we were truly aware that this was an approvability issue for the agency," Bradbury said in a response to questions. "The agency did request the tQT study that was done for Byetta during the timing of the review. This study was completed back in 2009. So, they certainly were reviewing it. However, we were not aware that this was an approvability issue until we received the complete response letter last night."
But as TheStreet points out, he did not mention that Amylin never informed the FDA about the tQT study when it was conducted and the agency did not know of its existence until they were told by Health Canada. And Bradbury did not say the study raised safety concerns related to Bydureon or that Amylin was aware due to the action of Canadian regulators, at least according to the version of events noted in the Parks memo.
In any event, one analyst asked this on the conference: "...was the thorough QT study required for Byetta or is this Bydureon a unique request?" What does Bradbury say: "So, that's a great question. The tQT study wasn't required through the initial approval in the US of Byetta. It was requested by another agency for us to complete and we did that for them. It is now, I believe, a requirement. This is part of the evolution of the increase in focus on cardiovascular safety for all medicines, particularly those in diabetes. It is now a requirement for all medicines in diabetes to have a tQT study, as far as I'm aware."
This was an interesting choice of words. Bradbury never mentioned that Amylin did not act transparently and failed to provide the FDA with the study, or that the FDA wanted to see the study in order to assess Bydureon safety. And as TheStreet writes, the data would most likely been an issue if the FDA been aware of the study from the beginning.
Ironically, on a subsequent conference call with analysts, one thanked Amlylin execs for their transparency. "Hey guys. Thanks for all the disclosure. I think I speak for everybody, you guys handled this well. We appreciate it." How does Bradbury respond? "I appreciate your kind remarks with regards to disclosure. We do try very hard to be as transparent as possible with everybody about what we know about the business."