Will mineral-oil placebo torpedo Vascepa's game-changing CV label? FDA committee will decide
An FDA advisory committee will scrutinize a mineral-oil placebo used in a CV outcomes trial for Amarin's Vascepa. (Amarin)
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.
Using AI and RWD to Uncover Rare Disease Insights, Accelerate Commercialization and Improve Patient Outcomes
Wednesday, March 24 | 2pm ET / 11am PT
Learn how IPM.ai transformed real world data into real world insights to assist Audentes in their development of AT132 for the treatment of XLMTM. The session reviews how IPM.ia and Audentes collaborated to uncover the XLMTM patient population.
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.