Since the active ingredient in Byetta and Bydureon is the same, Amylin asked FDA to rely on efficacy and safety data from Byetta clinical trials for part of the regulatory review of Bydureon. FDA agreed to Amylin's request.
Amylin submitted Bydureon for approval in May 2009 but FDA rejected the drug in March 2010, citing the completion of a risk management plan and resolution of some product quality issues as the only deficiencies needed to be remedied.
One month later, in April 2010, regulators with Health Canada told FDA about a "thorough QT study" of Byetta conducted two years earlier by the company. So-called tQT studies measure the effect a drug has on heart rhythm, an especially important issue to FDA given concerns about the cardiovascular safety of diabetes drugs. This tQT study of Byetta raised significant heart safety concerns for Canadian regulators.
But Amylin had never told FDA about the tQT study of Byetta and failed to include the troublesome heart-safety data in the initial Byduron approval filing. Amylin withheld these negative safety data even though Amylin agreed to supply FDA with Byetta efficacy and safety data for use in the Bydureon review, FDA's Parks charges in her 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 writes.
Immediately upon learning of the existence of the Byetta tQT study, FDA contacted Amylin and asked for the data to be included in the Bydureon resubmission. Amylin resubmitted its Bydureon application on April 22, 2010 but data from the Byetta tQT study were "absent" from the filing, Park states in her memo.
Instead, Amylin submitted the Byetta tQT study data separately as an addendum to the original Byetta regulatory file. Asked whether Amylin was trying to conceal potential negative heart-safety data from FDA, Amylin spokeswoman Izzo says the company notified FDA in an "appropriate manner."
Regardless of how the previously undisclosed Byetta heart-safety study was filed, FDA considered the data as part of Amylin's Bydureon resubmission. On Oct. 18, 2010, FDA rejected Bydureon a second time, in part over the safety concerns raised by the Byetta heart safety study conducted in Canada.