The long-awaited results of the Vytorin Enhance trial announced in January, which found the drug lowered “bad” or LDL cholesterol in the blood more effectively than simvastatin alone, but was no better at preventing atherosclerosis, precipitated a 33% plunge in Schering-Plough’s share price, a 26% drop at Merck & Co, and caused sales of the combination pill to fall 18%.
Commentators have little confidence that the presentation of the full data set at The American College of Cardiologists (ACC) meeting this week will lead to a significant rebound, in either share prices or sales. More influential could be the panel discussion that follows.
The ACC have assembled an independent panel, and the chair of the scientific session, cardiologist Marc Shelton, has said they have been charged with coming up with a recommendation of how they would treat patients in the future.
Considering 16,600 people have pre-registered for the conference, up 29% from last year's ACC, the panel's opinion could have a significant impact. Latest IMS data shows Vytorin's share of new statin prescriptions has dropped to 7.9% from 10% prior to the Enhance data released in January. This fall has mainly been taken up by increased share for generic simvastatin.
The headline results have already convinced many doctors that using Vytorin, a combination of statin Zocor and lipid-lowering agent Zetia, was no longer justifiable, on both price and efficacy grounds. Because Enhance was not designed to prove Vytorin lowered the risk of heart attack or stroke, those opinions will be hard to change. What could happen is a shift in perception, if the full results are notably more positive or negative from the first read out, or if the panel voices particularly strong opinions either way.
Vytorin forecasts have already come down significantly. Sales are seen dipping slightly this year from 2007, to $2.38bn, and consensus for 2012 sales currently sits at $3.45m, down from $4.95m at the beginning of the year, archived forecasts from EvaluatePharma show.
The spread of forecasts in 2012 is wide, from $2.49bn to $4.03bn, reflecting the uncertain future of the franchise. An idea of which looks a more accurate estimate of future performance might be gleaned from the panel comments, and analysts will be trying to gauge whether the overall opinions of the drug have altered in any way.
Opinions will be hard to change because lipid-lowering agents like Zetia have yet to prove they lower the risk of cardiac events. The link between lowering cholesterol, which is what statins achieve by blocking an enzyme in the liver, and a reduced risk of heart attack or stroke is widely accepted. Zetia works by absorbing cholesterol in the digestive tract.
The fact that Zetia failed to prevent a thickening of the arteries any more effectively than a generic statin, and whether this has any bearing on morbidity and mortality rates, will be a key conversation point.
Evidence for the link will come with the read out from another Vytorin trial, called Improve-IT, an outcome trial which should be available in 2011. Only a positive results from that trial, or evidence in the meantime that lipid-lowering drugs lower cardiac risk, are likely to give Vytorin sales a significant boost.