In surprising setback for Merck, FDA panel refuses to back broader Zetia indication
- Merck's hopes to win approval of a label expansion for Zetia (ezetimbe) through the combo drug Vytorin (ezetimbe/simvastatin) to include reduction of CVD risk took a blow on Monday as an FDA advisory committee voted 10-5 against endorsing Merck's claims for the drug.
- Results from Merck's Improve-It, a long-term outcomes trial involving 18,144 patients with acute coronary syndrome (ACS), showed that adding Zetia to simvastatin decreased risk of CV events. However, panel members did not believe that the benefit was significant.
- Zetia generated $2.86 billion in revenues last year, but will lose patent protection in 2016.
As a non-statin, anti-cholesterol drug, Zetia has been a second-line treatment for patients who either can't tolerate statins or whose LDL-C cannot be properly lowered with statins. However, the latest data from the Improve-It trial wasn't enough to persuade the FDA's advisory committee to recommend approval for an expanded label.
In the trial, 30.2% of patients in the simvastatin-only treatment cohort experienced a CV event, compared with 28.4% of patients in the Zetia-plus-simvastatin cohort. However, subgroup analysis has shown most of the beneficial effects were experienced by patients with diabetes. In fact, according to an FDA reviewer, there was "no effect seen among the under 75, non-diabetic subgroup, which were a majority of the study population," as reported by Cardio Brief.
In addition pursuing this CV-related indication for Zetia, Merck also wants the drug to be approved for addition to any statin treatment, not just simvastatin. Given the very low costs of generic statins (especially compared to the new PCSK9 inhibitors hitting the market), this combination could be both cost-effective and clinically effective. Furthermore, patients who have not achieved LDL-C reduction with statins alone could be treated next by adding ezetimbe, instead of moving straight to the more-expensive PCSK9 inhibitors.
But now, the question is whether or not the FDA will go along with the advisory committee's suprising decision.