A closely watched study of the Vytorin cholesterol pill was cleared to continue by a Data Safety Monitoring Board, confirming most Wall Street expectations that the so-called IMPROVE-IT trial would not be stopped for problems concerning safety or efficacy. However, Merck did not release any data and says the study may not end by 2013, as planned, since the monitoring board will take another look at the data in nine months.
Merck hopes the trial will show that Vytorin can outperform its Zocor pill in preventing deaths, heart attacks and strokes. Vytorin combines Zocor with Zetia. Vytorin may be what Sanford Bernstein analyst Tim Anderson called a "maligned brand" in an investor note today, but Merck, of course, would like a boost to its cholesterol franchise. Last year, combined revenue from Vytorin and Zetia was $4.3 billion last year, or 9 percent of companywide sales, but has largely stalled.
The 18,000-patient IMPROVE-IT trial is supposed to resolve questions raised by the controversial Enhance trial, which was released in 2008 and found Vytorin failed to show a benefit over Zocor in reducing plaque in the carotid artery, and showed a statistically insignificant buildup. Vytorin did a better job of lowering LDL, but was no better than an inexpensive statin in patients with familial hypercholesterolaemia, an inherited form of high cholesterol.
At the time, Merck and Schering-Plough - which was its partner but now, of course, is owned by the large drugmaker - were criticized for changing the primary endpoint, which was done without the knowledge of the lead investigator (look here) and repeatedly delayed reporting results. That raised questions about whether patients received sufficient benefit for a heavily promoted and expensive pill (see this).
The handling of the Enhance trial prompted a derivative shareholder lawsuit that was recently settled in which Merck agreed to a corporate governance change. Once a year, the Merck Research Laboratories unit will submit a report to the board of directors research committee regarding any clinical trial where results have been delayed, including the reasons for the delay in reporting those results and any action taken to speed things up (see here). As it so happens, Merck hired a new compliance officer today - Mike Holston from Hewlett-Packard (read this).
To what extent positive results can make much difference for Merck is unclear, though. Opinions are divided about the probability that a positive outcome will vastly improve (pun intended) the prospects for the drugmaker. "We continue to believe that IMPROVE-IT may not matter that much anymore, in terms of having a meaningful impact on Merck’s share price," Bernstein's Anderson writes.
He points out that a good outcome would be "vindicating" for Merck, but might also be a case of "too little, too late," because AstraZeneca's Crestor pill stepped in to fill the void created by the controversy over the Enhance trial. And more recently, generic versions of Pfizer's Lipitor pill are on the market. "Even with a new round of heavy advertising – something Merck walked away from after Enhance came out – Vytorin could still find itself limping along," Anderson writes.
Taking a contrarian view is ISI Group analyst Mark Schoenebaum, who writes in his own note this morning that "our read in this event-driven trial is that events are simply accruing more slowly than expected and we view the events (and the additional look given an extended trial) as overall neutral." But he then adds that "...we view any win as a big upside. We view IMPROVE-IT as the single biggest reason (investors) don’t own Merck (stock), but think the trial has a reasonable probability of success."
The safety monitors conducted the interim analysis after the trial reached 75 percent of the 5,250 clinical events called for in the design of the study (here is the Merck statement). Zocor, by the way, is now available as a generic known as simvastatin.
pic thx to alan_cleaver on flickr