Merck & Co has failed to convince an FDA advisory committee that labelling for its cholesterol-lowering drug Vytorin should include a claim of reducing heart attacks and strokes.
The panel reviewed data from the large-scale IMPROVE-IT trial at a meeting yesterday but were not swayed by the data and voted 10 to 5 to reject the proposed label change.
IMPROVE-IT involved 18,000 high-risk patients with acute coronary syndromes (ACS) – including unstable angina and heart attacks – and compared Vytorin (ezetimibe and simvastatin) to simvastatin alone for their ability to reduce major cardiovascular events.
The trial started around 10 years ago – shortly after Vytorin was launched onto the market – with final results published last year.
It found a modest benefit with the addition of CETP inhibitor ezetimibe (Merck’s Zetia) to the statin; 32.7% of the combination group suffered a major cardiovascular event over a median seven-year follow-up period, compared to 34.7% of the simvastatin group.
Vytorin has been a big seller for Merck with sales of $942m in the first nine months of the year although it has trailed behind sales of the single-agent brand Zetia, which brought in $1.8bn in the same period.
Sales of both products have started to slip thanks to the loss of patent protection in some markets such as Canada, as well as prescribing restrictions in France, and being able to promote a new label claim could have injected some additional momentum into the franchise.
“Today’s discussion is one step in the regulatory process,” said Merck in a statement. “We believe that IMPROVE-IT showed that ezetimibe in combination with a statin offers a significant benefit to high-risk patients with coronary heart disease and are committed to continuing to work with the FDA so that they can complete the review.”
Regardless of the outcome of the FDA’s deliberations, Merck will face further generic competition to Zetia and Vytorin towards the end of next year when its patents in the US expire.
Vytorin has been a somewhat controversial product for Merck since the publication of the ENHANCE trial, which compared the drug to simvastatin (Merck’s now off-patent brand Zocor) alone in preventing the progression of atherosclerosis but found no additional benefit.
In 2013, Merck agreed to pay $688m to settle investor claims that it delayed disclosure of the ENHANCE results.