Just two days before Amarin faces a pivotal FDA advisory committee to expand its label for fish-oil derivative Vascepa, the FDA has some questions about the key trial's placebo control—namely, whether it skewed the drug's "landmark" cardiovascular outcomes results.
FDA documents posted ahead of Thursday's meeting show staff reviewers have zeroed in on the mineral oil placebo used in Vascepa's phase 3 Reduce-It trial. The choice of placebo may have flattered Vascepa's performance, said John Sharretts, acting deputy director of the FDA's division of metabolism and endocrinology products, in a briefing for Thursday's advisory committee meeting.
The trial tested Vascepa as an add-on to statin therapy, compared with the mineral oil placebo paired with statins. Sharretts said the FDA was examining whether that mineral oil interfered with patients' ability to absorb statin therapy, artificially raising patients' cholesterol levels and skewing Vascepa's results in the trial.
However, Sharretts noted that the FDA's own study of mineral oil's effects on statin absorption was "inconclusive."
"Due to lack of certain key measurements, we could neither rule out the possibility that mineral oil––at least to some extent––interfered with statin absorption, nor estimate the magnitude of LDL-C or other biomarker increase that could be attributed to such an interaction," Sharretts wrote in the review documents.
He went on to instruct the committee to weigh the questions. "From the scientific perspective, therefore, it remains necessary to consider what impact the increase in LDL-C and other biomarkers had on CV outcomes, Sharretts said.
